[Development of intellect, emotion, and intentions, and their neuronal systems].

PubMed

Segawa, Masaya

2008-09-01

Intellect, emotion and intentions, the major components of the human mentality, are neurologically correlated to memory and sensorimotor integration, the neuronal system consisting of the amygdale and hypothalamus, and motivation and learning, respectively. Development of these neuronal processes was evaluated by correlating the pathophysiologies of idiopathic developmental neuropsychiatric disorders and developmental courses of sleep parameters, sleep-wake rhythm (SWR), and locomotion. The memory system and sensory pathways develop by the 9th gestational months. Habituation or dorsal bundle extinction (DBE) develop after the 34th gestational week. In the first 4 months after birth, DBE is consolidated and fine tuning of the primary sensory cortex and its neuronal connection to the unimodal sensory association area along with functional lateralization of the cortex are accomplished. After 4 months, restriction of atonia in the REM stage enables the integrative function of the brain and induces synaptogenesis of the cortex around 6 months and locomotion in late infancy by activating the dopaminergic (DA) neurons induces synaptogenesis of the frontal cortex. Locomotion in early infancy involves functional specialization of the cortex and in childhood with development of biphasic SWR activation of the areas of the prefrontal cortex. Development of emotions reflects in the development of personal communication and the arousal function of the hypothalamus. The former is shown in the mother-child relationship in the first 4 months, in communication with adults and playmates in late infancy to early childhood, and in development of social relationships with sympathy by the early school age with functional maturation of the orbitofrontal cortex. The latter is demonstrated in the secretion of melatonin during night time by 4 months, in the circadian rhythm of body temperature by 8 months, and in the secretion of the growth hormone by 4-5 years with synchronization to the SWR modulated by the brainstem aminergic neurons. For this purpose, nursing according to the day-night light-dark cycle is essential right from early infancy. The deep cerebellar nuclei involved in learning develop by the 9th gestational month. The DA neurons activated in late infancy modulate the nuclei of the basal ganglia and the association cortex for learning. Motivation starts with activation of the PPN in infancy by crawling which makes DA neurons as the lead. In late childhood, DA neurons along with 5HT neurons activate the anterior cingulate area and establish the neuronal process for learning with motivation.

Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.

PubMed

Hussin, Ahmed T; Boychuk, Jeffery A; Brown, Andrew R; Pittman, Quentin J; Teskey, G Campbell

2015-01-01

Intracortical microstimulation (ICMS) is a technique used for a number of purposes including the derivation of cortical movement representations (motor maps). Its application can activate the output layer 5 of motor cortex and can result in the elicitation of body movements depending upon the stimulus parameters used. The extent to which pyramidal tract projection neurons of the motor cortex are activated transsynaptically or directly by ICMS remains an open question. Given this uncertainty in the mode of activation, we used a preparation that combined patch clamp whole-cell recordings from single layer 5 pyramidal neurons and extracellular ICMS in slices of motor cortex as well as a standard in vivo mapping technique to ask how ICMS activated motor cortex pyramidal neurons. We measured changes in synaptic spike threshold and spiking rate to ICMS in vitro and movement threshold in vivo in the presence or absence of specific pharmacological blockers of glutamatergic (AMPA, NMDA and Kainate) receptors and GABAA receptors. With major excitatory and inhibitory synaptic transmission blocked (with DNQX, APV and bicuculline methiodide), we observed a significant increase in the ICMS current intensity required to elicit a movement in vivo as well as to the first spike and an 85% reduction in spiking responses in vitro. Subsets of neurons were still responsive after the synaptic block, especially at higher current intensities, suggesting a modest direct activation. Taken together our data indicate a mainly synaptic mode of activation to ICMS in layer 5 of rat motor cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex.

PubMed

Major, Alex J; Vijayraghavan, Susheel; Everling, Stefan

2018-01-31

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system. Copyright © 2018 the authors 0270-6474/18/381137-14$15.00/0.

Electrical activity controls area-specific expression of neuronal apoptosis in the mouse developing cerebral cortex.

PubMed

Blanquie, Oriane; Yang, Jenq-Wei; Kilb, Werner; Sharopov, Salim; Sinning, Anne; Luhmann, Heiko J

2017-08-21

Programmed cell death widely but heterogeneously affects the developing brain, causing the loss of up to 50% of neurons in rodents. However, whether this heterogeneity originates from neuronal identity and/or network-dependent processes is unknown. Here, we report that the primary motor cortex (M1) and primary somatosensory cortex (S1), two adjacent but functionally distinct areas, display striking differences in density of apoptotic neurons during the early postnatal period. These differences in rate of apoptosis negatively correlate with region-dependent levels of activity. Disrupting this activity either pharmacologically or by electrical stimulation alters the spatial pattern of apoptosis and sensory deprivation leads to exacerbated amounts of apoptotic neurons in the corresponding functional area of the neocortex. Thus, our data demonstrate that spontaneous and periphery-driven activity patterns are important for the structural and functional maturation of the neocortex by refining the final number of cortical neurons in a region-dependent manner.

Integrative Mechanisms of Oriented Neuronal Migration in the Developing Brain

PubMed Central

Evsyukova, Irina; Plestant, Charlotte; Anton, E.S.

2014-01-01

The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization. PMID:23937349

Use of a simplified method of optical recording to identify foci of maximal neuron activity in the somatosensory cortex of white rats.

PubMed

Inyushin, M Y; Volnova, A B; Lenkov, D N

2001-01-01

Eight mongrel white male rats were studied under urethane anesthesia, and neuron activity evoked by mechanical and/or electrical stimulation of the contralateral whiskers was recorded in the primary somatosensory cortex. Recordings were made using a digital USB chamber attached to the printer port of a Pentium 200MMX computer running standard programs. Optical images were obtained in the barrel-field zone using a differential signal, i.e., the difference signal for cortex images in control and experimental animals. The results obtained here showed that subtraction of averaged sequences of frames yielded images consisting of spots reflecting the probable position of activated groups of neurons. The most effective stimulation consisted of natural low-frequency stimulation of the whiskers. The method can be used for preliminary mapping of cortical zones, as it provides for rapid and reproducible testing of the activity of neuron ensembles over large areas of the cortex.

A Map of Anticipatory Activity in Mouse Motor Cortex.

PubMed

Chen, Tsai-Wen; Li, Nuo; Daie, Kayvon; Svoboda, Karel

2017-05-17

Activity in the mouse anterior lateral motor cortex (ALM) instructs directional movements, often seconds before movement initiation. It is unknown whether this preparatory activity is localized to ALM or widely distributed within motor cortex. Here we imaged activity across motor cortex while mice performed a whisker-based object localization task with a delayed, directional licking response. During tactile sensation and the delay epoch, object location was represented in motor cortex areas that are medial and posterior relative to ALM, including vibrissal motor cortex. Preparatory activity appeared first in deep layers of ALM, seconds before the behavioral response, and remained localized to ALM until the behavioral response. Later, widely distributed neurons represented the outcome of the trial. Cortical area was more predictive of neuronal selectivity than laminar location or axonal projection target. Motor cortex therefore represents sensory, motor, and outcome information in a spatially organized manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between individual neuron and network spontaneous activity in developing mouse cortex.

PubMed

Barnett, Heather M; Gjorgjieva, Julijana; Weir, Keiko; Comfort, Cara; Fairhall, Adrienne L; Moody, William J

2014-12-15

Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous central nervous system structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex, which participates in, but does not initiate, SSA (Lischalk JW, Easton CR, Moody WJ. Dev Neurobiol 69: 407-414, 2009). In this study, we used Ca(2+) imaging of cultured embryonic day 18 to postnatal day 2 coronal slices (embryonic day 17 + 1-4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons was active asynchronously between waves, and a larger number of groups of coactive cells was present compared with the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained, while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation. Copyright © 2014 the American Physiological Society.

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

PubMed

Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

2017-01-06

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

Layer-specific excitation/inhibition balances during neuronal synchronization in the visual cortex.

PubMed

Adesnik, Hillel

2018-05-01

Understanding the balance between synaptic excitation and inhibition in cortical circuits in the brain, and how this contributes to cortical rhythms, is fundamental to explaining information processing in the cortex. This study used cortical layer-specific optogenetic activation in mouse cortex to show that excitatory neurons in any cortical layer can drive powerful gamma rhythms, while inhibition balances excitation. The net impact of this is to keep activity within each layer in check, but simultaneously to promote the propagation of activity to downstream layers. The data show that rhythm-generating circuits exist in all principle layers of the cortex, and provide layer-specific balances of excitation and inhibition that affect the flow of information across the layers. Rhythmic activity can synchronize neural ensembles within and across cortical layers. While gamma band rhythmicity has been observed in all layers, the laminar sources and functional impacts of neuronal synchronization in the cortex remain incompletely understood. Here, layer-specific optogenetic stimulation demonstrates that populations of excitatory neurons in any cortical layer of the mouse's primary visual cortex are sufficient to powerfully entrain neuronal oscillations in the gamma band. Within each layer, inhibition balances excitation and keeps activity in check. Across layers, translaminar output overcomes inhibition and drives downstream firing. These data establish that rhythm-generating circuits exist in all principle layers of the cortex, but provide layer-specific balances of excitation and inhibition that may dynamically shape the flow of information through cortical circuits. These data might help explain how excitation/inhibition (E/I) balances across cortical layers shape information processing, and shed light on the diverse nature and functional impacts of cortical gamma rhythms. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex.

PubMed

Jasmin, Luc; Rabkin, Samuel D; Granato, Alberto; Boudah, Abdennacer; Ohara, Peter T

2003-07-17

It is known that pain perception can be altered by mood, attention and cognition, or by direct stimulation of the cerebral cortex, but we know little of the neural mechanisms underlying the cortical modulation of pain. One of the few cortical areas consistently activated by painful stimuli is the rostral agranular insular cortex (RAIC) where, as in other parts of the cortex, the neurotransmitter gamma-aminobutyric acid (GABA) robustly inhibits neuronal activity. Here we show that changes in GABA neurotransmission in the RAIC can raise or lower the pain threshold--producing analgesia or hyperalgesia, respectively--in freely moving rats. Locally increasing GABA, by using an enzyme inhibitor or gene transfer mediated by a viral vector, produces lasting analgesia by enhancing the descending inhibition of spinal nociceptive neurons. Selectively activating GABA(B)-receptor-bearing RAIC neurons produces hyperalgesia through projections to the amygdala, an area involved in pain and fear. Whereas most studies focus on the role of the cerebral cortex as the end point of nociceptive processing, we suggest that cerebral cortex activity can change the set-point of pain threshold in a top-down manner.

RNA sequencing from neural ensembles activated during fear conditioning in the mouse temporal association cortex

PubMed Central

Cho, Jin-Hyung; Huang, Ben S.; Gray, Jesse M.

2016-01-01

The stable formation of remote fear memories is thought to require neuronal gene induction in cortical ensembles that are activated during learning. However, the set of genes expressed specifically in these activated ensembles is not known; knowledge of such transcriptional profiles may offer insights into the molecular program underlying stable memory formation. Here we use RNA-Seq to identify genes whose expression is enriched in activated cortical ensembles labeled during associative fear learning. We first establish that mouse temporal association cortex (TeA) is required for remote recall of auditory fear memories. We then perform RNA-Seq in TeA neurons that are labeled by the activity reporter Arc-dVenus during learning. We identify 944 genes with enriched expression in Arc-dVenus+ neurons. These genes include markers of L2/3, L5b, and L6 excitatory neurons but not glial or inhibitory markers, confirming Arc-dVenus to be an excitatory neuron-specific but non-layer-specific activity reporter. Cross comparisons to other transcriptional profiles show that 125 of the enriched genes are also activity-regulated in vitro or induced by visual stimulus in the visual cortex, suggesting that they may be induced generally in the cortex in an experience-dependent fashion. Prominent among the enriched genes are those encoding potassium channels that down-regulate neuronal activity, suggesting the possibility that part of the molecular program induced by fear conditioning may initiate homeostatic plasticity. PMID:27557751

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.

PubMed

DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire

2016-10-05

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship emphasizes the importance of the behavioral procedure to engage the motor cortex during motor control studies, gait rehabilitation, and locomotor neuroprosthetic developments in rats. Copyright © 2016 the authors 0270-6474/16/3610440-16$15.00/0.

Motivation and Affective Judgments Differentially Recruit Neurons in the Primate Dorsolateral Prefrontal and Anterior Cingulate Cortex

PubMed Central

Amemori, Ken-ichi; Amemori, Satoko

2015-01-01

The judgment of whether to accept or to reject an offer is determined by positive and negative affect related to the offer, but affect also induces motivational responses. Rewarding and aversive cues influence the firing rates of many neurons in primate prefrontal and cingulate neocortical regions, but it still is unclear whether neurons in these regions are related to affective judgment or to motivation. To address this issue, we recorded simultaneously the neuronal spike activities of single units in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC) of macaque monkeys as they performed approach–avoidance (Ap–Av) and approach–approach (Ap–Ap) decision-making tasks that can behaviorally dissociate affective judgment and motivation. Notably, neurons having activity correlated with motivational condition could be distinguished from neurons having activity related to affective judgment, especially in the Ap–Av task. Although many neurons in both regions exhibited similar, selective patterns of task-related activity, we found a larger proportion of neurons activated in low motivational conditions in the dlPFC than in the ACC, and the onset of this activity was significantly earlier in the dlPFC than in the ACC. Furthermore, the temporal onsets of affective judgment represented by neuronal activities were significantly slower in the low motivational conditions than in the other conditions. These findings suggest that motivation and affective judgment both recruit dlPFC and ACC neurons but with differential degrees of involvement and timing. PMID:25653353

Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons.

PubMed

Prsa, Mario; Galiñanes, Gregorio L; Huber, Daniel

2017-02-22

Neuronal motor commands, whether generating real or neuroprosthetic movements, are shaped by ongoing sensory feedback from the displacement being produced. Here we asked if cortical stimulation could provide artificial feedback during operant conditioning of cortical neurons. Simultaneous two-photon imaging and real-time optogenetic stimulation were used to train mice to activate a single neuron in motor cortex (M1), while continuous feedback of its activity level was provided by proportionally stimulating somatosensory cortex. This artificial signal was necessary to rapidly learn to increase the conditioned activity, detect correct performance, and maintain the learned behavior. Population imaging in M1 revealed that learning-related activity changes are observed in the conditioned cell only, which highlights the functional potential of individual neurons in the neocortex. Our findings demonstrate the capacity of animals to use an artificially induced cortical channel in a behaviorally relevant way and reveal the remarkable speed and specificity at which this can occur. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Switching modes in corticogenesis: mechanisms of neuronal subtype transitions and integration in the cerebral cortex

PubMed Central

Toma, Kenichi; Hanashima, Carina

2015-01-01

Information processing in the cerebral cortex requires the activation of diverse neurons across layers and columns, which are established through the coordinated production of distinct neuronal subtypes and their placement along the three-dimensional axis. Over recent years, our knowledge of the regulatory mechanisms of the specification and integration of neuronal subtypes in the cerebral cortex has progressed rapidly. In this review, we address how the unique cytoarchitecture of the neocortex is established from a limited number of progenitors featuring neuronal identity transitions during development. We further illuminate the molecular mechanisms of the subtype-specific integration of these neurons into the cerebral cortex along the radial and tangential axis, and we discuss these key features to exemplify how neocortical circuit formation accomplishes economical connectivity while maintaining plasticity and evolvability to adapt to environmental changes. PMID:26321900

Axonal synapse sorting in medial entorhinal cortex

NASA Astrophysics Data System (ADS)

Schmidt, Helene; Gour, Anjali; Straehle, Jakob; Boergens, Kevin M.; Brecht, Michael; Helmstaedter, Moritz

2017-09-01

Research on neuronal connectivity in the cerebral cortex has focused on the existence and strength of synapses between neurons, and their location on the cell bodies and dendrites of postsynaptic neurons. The synaptic architecture of individual presynaptic axonal trees, however, remains largely unknown. Here we used dense reconstructions from three-dimensional electron microscopy in rats to study the synaptic organization of local presynaptic axons in layer 2 of the medial entorhinal cortex, the site of grid-like spatial representations. We observe path-length-dependent axonal synapse sorting, such that axons of excitatory neurons sequentially target inhibitory neurons followed by excitatory neurons. Connectivity analysis revealed a cellular feedforward inhibition circuit involving wide, myelinated inhibitory axons and dendritic synapse clustering. Simulations show that this high-precision circuit can control the propagation of synchronized activity in the medial entorhinal cortex, which is known for temporally precise discharges.

Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning.

PubMed

Whitaker, Leslie R; Warren, Brandon L; Venniro, Marco; Harte, Tyler C; McPherson, Kylie B; Beidel, Jennifer; Bossert, Jennifer M; Shaham, Yavin; Bonci, Antonello; Hope, Bruce T

2017-09-06

Learned associations between environmental stimuli and rewards drive goal-directed learning and motivated behavior. These memories are thought to be encoded by alterations within specific patterns of sparsely distributed neurons called neuronal ensembles that are activated selectively by reward-predictive stimuli. Here, we use the Fos promoter to identify strongly activated neuronal ensembles in rat prelimbic cortex (PLC) and assess altered intrinsic excitability after 10 d of operant food self-administration training (1 h/d). First, we used the Daun02 inactivation procedure in male FosLacZ-transgenic rats to ablate selectively Fos-expressing PLC neurons that were active during operant food self-administration. Selective ablation of these neurons decreased food seeking. We then used male FosGFP-transgenic rats to assess selective alterations of intrinsic excitability in Fos-expressing neuronal ensembles (FosGFP + ) that were activated during food self-administration and compared these with alterations in less activated non-ensemble neurons (FosGFP - ). Using whole-cell recordings of layer V pyramidal neurons in an ex vivo brain slice preparation, we found that operant self-administration increased excitability of FosGFP + neurons and decreased excitability of FosGFP - neurons. Increased excitability of FosGFP + neurons was driven by increased steady-state input resistance. Decreased excitability of FosGFP - neurons was driven by increased contribution of small-conductance calcium-activated potassium (SK) channels. Injections of the specific SK channel antagonist apamin into PLC increased Fos expression but had no effect on food seeking. Overall, operant learning increased intrinsic excitability of PLC Fos-expressing neuronal ensembles that play a role in food seeking but decreased intrinsic excitability of Fos - non-ensembles. SIGNIFICANCE STATEMENT Prefrontal cortex activity plays a critical role in operant learning, but the underlying cellular mechanisms are unknown. Using the chemogenetic Daun02 inactivation procedure, we found that a small number of strongly activated Fos-expressing neuronal ensembles in rat PLC play an important role in learned operant food seeking. Using GFP expression to identify Fos-expressing layer V pyramidal neurons in prelimbic cortex (PLC) of FosGFP-transgenic rats, we found that operant food self-administration led to increased intrinsic excitability in the behaviorally relevant Fos-expressing neuronal ensembles, but decreased intrinsic excitability in Fos - neurons using distinct cellular mechanisms. Copyright © 2017 the authors 0270-6474/17/378845-12$15.00/0.

SINGLE NEURON ACTIVITY AND THETA MODULATION IN POSTRHINAL CORTEX DURING VISUAL OBJECT DISCRIMINATION

PubMed Central

Furtak, Sharon C.; Ahmed, Omar J.; Burwell, Rebecca D.

2012-01-01

Postrhinal cortex, the rodent homolog of the primate parahippocampal cortex, processes spatial and contextual information. Our hypothesis of postrhinal function is that it serves to encode context, in part, by forming representations that link objects to places. We recorded postrhinal neuronal activity and local field potentials (LFPs) in rats trained on a two-choice, visual discrimination task. As predicted, a large proportion of postrhinal neurons signaled object-location conjunctions. In addition, postrhinal LFPs exhibited strong oscillatory rhythms in the theta band, and many postrhinal neurons were phase locked to theta. Although correlated with running speed, theta power was lower than predicted by speed alone immediately before and after choice. However, theta power was significantly increased following incorrect decisions, suggesting a role in signaling error. These findings provide evidence that postrhinal cortex encodes representations that link objects to places and suggest that postrhinal theta modulation extends to cognitive as well as spatial functions. PMID:23217745

Viewing speech modulates activity in the left SI mouth cortex.

PubMed

Möttönen, Riikka; Järveläinen, Juha; Sams, Mikko; Hari, Riitta

2005-02-01

The ability to internally simulate other persons' actions is important for social interaction. In monkeys, neurons in the premotor cortex are activated both when the monkey performs mouth or hand actions and when it views or listens to actions made by others. Neuronal circuits with similar "mirror-neuron" properties probably exist in the human Broca's area and primary motor cortex. Viewing other person's hand actions also modulates activity in the primary somatosensory cortex SI, suggesting that the SI cortex is related to the human mirror-neuron system. To study the selectivity of the SI activation during action viewing, we stimulated the lower lip (with tactile pulses) and the median nerves (with electric pulses) in eight subjects to activate their SI mouth and hand cortices while the subjects either rested, listened to other person's speech, viewed her articulatory gestures, or executed mouth movements. The 55-ms SI responses to lip stimuli were enhanced by 16% (P<0.01) in the left hemisphere during speech viewing whereas listening to speech did not modulate these responses. The 35-ms responses to median-nerve stimulation remained stable during speech viewing and listening. Own mouth movements suppressed responses to lip stimuli bilaterally by 74% (P<0.001), without any effect on responses to median-nerve stimuli. Our findings show that viewing another person's articulatory gestures activates the left SI cortex in a somatotopic manner. The results provide further evidence for the view that SI is involved in "mirroring" of other persons' actions.

Neural dynamics and information representation in microcircuits of motor cortex.

PubMed

Tsubo, Yasuhiro; Isomura, Yoshikazu; Fukai, Tomoki

2013-01-01

The brain has to analyze and respond to external events that can change rapidly from time to time, suggesting that information processing by the brain may be essentially dynamic rather than static. The dynamical features of neural computation are of significant importance in motor cortex that governs the process of movement generation and learning. In this paper, we discuss these features based primarily on our recent findings on neural dynamics and information coding in the microcircuit of rat motor cortex. In fact, cortical neurons show a variety of dynamical behavior from rhythmic activity in various frequency bands to highly irregular spike firing. Of particular interest are the similarity and dissimilarity of the neuronal response properties in different layers of motor cortex. By conducting electrophysiological recordings in slice preparation, we report the phase response curves (PRCs) of neurons in different cortical layers to demonstrate their layer-dependent synchronization properties. We then study how motor cortex recruits task-related neurons in different layers for voluntary arm movements by simultaneous juxtacellular and multiunit recordings from behaving rats. The results suggest an interesting difference in the spectrum of functional activity between the superficial and deep layers. Furthermore, the task-related activities recorded from various layers exhibited power law distributions of inter-spike intervals (ISIs), in contrast to a general belief that ISIs obey Poisson or Gamma distributions in cortical neurons. We present a theoretical argument that this power law of in vivo neurons may represent the maximization of the entropy of firing rate with limited energy consumption of spike generation. Though further studies are required to fully clarify the functional implications of this coding principle, it may shed new light on information representations by neurons and circuits in motor cortex.

[Effect of nootropic agents on impulse activity of cerebral cortex neurons].

PubMed

Iasnetsov, V V; Pravdivtsev, V A; Krylova, I N; Kozlov, S B; Provornova, N A; Ivanov, Iu V; Iasnetsov, V V

2001-01-01

The effect of nootropes (semax, mexidol, and GVS-111) on the activity of individual neurons in various cerebral cortex regions was studied by microelectrode and microionophoresis techniques in cats immobilized by myorelaxants. It was established that the inhibiting effect of mexidol upon neurons in more than half of cases is prevented or significantly decreased by the GABA antagonists bicuculline and picrotoxin. The inhibiting effect of semax and GVS-111 upon neurons in more than half of cases is related to stimulation of the M-choline and NMDA receptors, respectively.

Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex

NASA Astrophysics Data System (ADS)

Ohki, Kenichi; Chung, Sooyoung; Ch'ng, Yeang H.; Kara, Prakash; Reid, R. Clay

2005-02-01

Neurons in the cerebral cortex are organized into anatomical columns, with ensembles of cells arranged from the surface to the white matter. Within a column, neurons often share functional properties, such as selectivity for stimulus orientation; columns with distinct properties, such as different preferred orientations, tile the cortical surface in orderly patterns. This functional architecture was discovered with the relatively sparse sampling of microelectrode recordings. Optical imaging of membrane voltage or metabolic activity elucidated the overall geometry of functional maps, but is averaged over many cells (resolution >100µm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400µm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.

Short-Term Memory Trace in Rapidly Adapting Synapses of Inferior Temporal Cortex

PubMed Central

Sugase-Miyamoto, Yasuko; Liu, Zheng; Wiener, Matthew C.; Optican, Lance M.; Richmond, Barry J.

2008-01-01

Visual short-term memory tasks depend upon both the inferior temporal cortex (ITC) and the prefrontal cortex (PFC). Activity in some neurons persists after the first (sample) stimulus is shown. This delay-period activity has been proposed as an important mechanism for working memory. In ITC neurons, intervening (nonmatching) stimuli wipe out the delay-period activity; hence, the role of ITC in memory must depend upon a different mechanism. Here, we look for a possible mechanism by contrasting memory effects in two architectonically different parts of ITC: area TE and the perirhinal cortex. We found that a large proportion (80%) of stimulus-selective neurons in area TE of macaque ITCs exhibit a memory effect during the stimulus interval. During a sequential delayed matching-to-sample task (DMS), the noise in the neuronal response to the test image was correlated with the noise in the neuronal response to the sample image. Neurons in perirhinal cortex did not show this correlation. These results led us to hypothesize that area TE contributes to short-term memory by acting as a matched filter. When the sample image appears, each TE neuron captures a static copy of its inputs by rapidly adjusting its synaptic weights to match the strength of their individual inputs. Input signals from subsequent images are multiplied by those synaptic weights, thereby computing a measure of the correlation between the past and present inputs. The total activity in area TE is sufficient to quantify the similarity between the two images. This matched filter theory provides an explanation of what is remembered, where the trace is stored, and how comparison is done across time, all without requiring delay period activity. Simulations of a matched filter model match the experimental results, suggesting that area TE neurons store a synaptic memory trace during short-term visual memory. PMID:18464917

Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

PubMed

McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

2013-01-09

Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

Insights into cortical mechanisms of behavior from microstimulation experiments

PubMed Central

Histed, Mark H.; Ni, Amy M.; Maunsell, John H.R.

2012-01-01

Even the simplest behaviors depend on a large number of neurons that are distributed across many brain regions. Because electrical microstimulation can change the activity of localized subsets of neurons, it has provided valuable evidence that specific neurons contribute to particular behaviors. Here we review what has been learned about cortical function from behavioral studies using microstimulation in animals and humans. Experiments that examine how microstimulation affects the perception of stimuli have shown that the effects of microstimulation are usually highly specific and can be related to the stimuli preferred by neurons at the stimulated site. Experiments that ask subjects to detect cortical microstimulation in the absence of other stimuli have provided further insights. Although subjects typically can detect microstimulation of primary sensory or motor cortex, they are generally unable to detect stimulation of most of cortex without extensive practice. With practice, however, stimulation of any part of cortex can become detected. These training effects suggest that some patterns of cortical activity cannot be readily accessed to guide behavior, but that the adult brain retains enough plasticity to learn to process novel patterns of neuronal activity arising anywhere in cortex. PMID:22307059

Motivation and affective judgments differentially recruit neurons in the primate dorsolateral prefrontal and anterior cingulate cortex.

PubMed

Amemori, Ken-ichi; Amemori, Satoko; Graybiel, Ann M

2015-02-04

The judgment of whether to accept or to reject an offer is determined by positive and negative affect related to the offer, but affect also induces motivational responses. Rewarding and aversive cues influence the firing rates of many neurons in primate prefrontal and cingulate neocortical regions, but it still is unclear whether neurons in these regions are related to affective judgment or to motivation. To address this issue, we recorded simultaneously the neuronal spike activities of single units in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC) of macaque monkeys as they performed approach-avoidance (Ap-Av) and approach-approach (Ap-Ap) decision-making tasks that can behaviorally dissociate affective judgment and motivation. Notably, neurons having activity correlated with motivational condition could be distinguished from neurons having activity related to affective judgment, especially in the Ap-Av task. Although many neurons in both regions exhibited similar, selective patterns of task-related activity, we found a larger proportion of neurons activated in low motivational conditions in the dlPFC than in the ACC, and the onset of this activity was significantly earlier in the dlPFC than in the ACC. Furthermore, the temporal onsets of affective judgment represented by neuronal activities were significantly slower in the low motivational conditions than in the other conditions. These findings suggest that motivation and affective judgment both recruit dlPFC and ACC neurons but with differential degrees of involvement and timing. Copyright © 2015 the authors 0270-6474/15/351939-15$15.00/0.

Force-related neuronal activity in two regions of the primate ventral premotor cortex.

PubMed

Hepp-Reymond, M C; Hüsler, E J; Maier, M A; Ql, H X

1994-05-01

Neuronal activity was recorded in the ventral premotor cortex of one monkey (Macaca fascicularis) trained to exert finely graded forces with thumb and index finger on a force sensor in a visuomotor step-tracking paradigm. Trials with two or three consecutive ramp-and-hold force steps were presented randomly. Most neurons displayed similar discharge patterns in the two- and three-step trials and were assigned to one of the following classes: phasic, phasic-tonic, tonic, decreasing, and mixed. For more than 50% of the neurons with tonic activity, positive or negative correlations between firing rate and force were statistically significant. The indices of force sensitivity were on average higher for the two-step than for the three-step trials, indicating that the correlations yielded linearity over only a limited force range. The force-related cells were located in two regions of the ventral premotor cortex. One group was ying rostrally within the inferior limb of the arcuate sulcus, from which microstimulation elicited movements of fingers and hand. In the other more caudal region, adjacent to the finger region of primary motor cortex, microstimulation was rarely effective, but all neurons had clear peripheral receptive fields on finger and hand. The data indicate that two populations of neurons, located in the ventral premotor cortex, are related to movement execution. Effective microstimulation also suggests that one of the populations has fairly direct access to the spinal motor apparatus.

Treatment of obstructive sleep apnoea-hypopnea syndrome by mandible advanced device reduced neuron apoptosis in frontal cortex of rabbits.

PubMed

Lu, Hai-Yan; Wang, Wen; Zhou, Zheng; Liu, Chun-Yan; Liu, Ye; Xiao, Wei; Dong, Fu-Sheng; Wang, Jie

2018-05-25

To investigate effects of mandible advanced device (MAD) therapy for obstructive sleep apnoea-hypopnea syndrome (OSAHS) on the neuron apoptosis and acetylcholine esterase activity in frontal cortex. Thirty male New Zealand white rabbits were randomly divided into three groups (n = 10 in each group): group OSAHS, group MAD, and control group. Hydrophilic polyacrylamide gel was injected into soft palate of the animals to induce OSAHS in group OSAHS and group MAD. The group MAD animals wore MAD to relief the obstructiveness. The control group was not given any treatment. Computed tomography (CT) examination of the upper airway and polysomnography (PSG) recordings were performed in supine position. All rabbits were induced to sleep in a supine position for 4 to 6 hours every day and were observed for consecutive 8 weeks. The frontal cortices of three groups were dissected and the neuron apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry. Acetylcholine esterase (AchE) activity in the frontal cortex was measured by spectrophotometry. The group OSAHS exhibited high neuron apoptosis rate and low AchE activity than those of group MAD and control group. The blood oxygen saturation was negatively correlated with neuronal apoptosis rate and positively correlated with AchE activity. Applying MAD in OSAHS animals significantly improve the neuronal damage and function deficits by apnoea-hypoxia caused by narrowed upper airway. This study provided evidence that MAD therapy for OSAHS can significantly decrease neuronal apoptosis and increase AchE activity in the frontal cortex.

Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

PubMed

Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

2017-07-01

Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex.

PubMed

Kajikawa, Yoshinao; Smiley, John F; Schroeder, Charles E

2017-10-18

Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. Copyright © 2017 the authors 0270-6474/17/3710139-15$15.00/0.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex

PubMed Central

Smiley, John F.; Schroeder, Charles E.

2017-01-01

Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed “local” (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. PMID:28924008

Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

PubMed Central

Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D.; Rubenstein, John L. R.; Anton, E. S.

2014-01-01

Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex. PMID:25535916

Optogenetic stimulation of a meso-scale human cortical model

NASA Astrophysics Data System (ADS)

Selvaraj, Prashanth; Szeri, Andrew; Sleigh, Jamie; Kirsch, Heidi

2015-03-01

Neurological phenomena like sleep and seizures depend not only on the activity of individual neurons, but on the dynamics of neuron populations as well. Meso-scale models of cortical activity provide a means to study neural dynamics at the level of neuron populations. Additionally, they offer a safe and economical way to test the effects and efficacy of stimulation techniques on the dynamics of the cortex. Here, we use a physiologically relevant meso-scale model of the cortex to study the hypersynchronous activity of neuron populations during epileptic seizures. The model consists of a set of stochastic, highly non-linear partial differential equations. Next, we use optogenetic stimulation to control seizures in a hyperexcited cortex, and to induce seizures in a normally functioning cortex. The high spatial and temporal resolution this method offers makes a strong case for the use of optogenetics in treating meso scale cortical disorders such as epileptic seizures. We use bifurcation analysis to investigate the effect of optogenetic stimulation in the meso scale model, and its efficacy in suppressing the non-linear dynamics of seizures.

Odor identity coding by distributed ensembles of neurons in the mouse olfactory cortex

PubMed Central

Roland, Benjamin; Deneux, Thomas; Franks, Kevin M; Bathellier, Brice; Fleischmann, Alexander

2017-01-01

Olfactory perception and behaviors critically depend on the ability to identify an odor across a wide range of concentrations. Here, we use calcium imaging to determine how odor identity is encoded in olfactory cortex. We find that, despite considerable trial-to-trial variability, odor identity can accurately be decoded from ensembles of co-active neurons that are distributed across piriform cortex without any apparent spatial organization. However, piriform response patterns change substantially over a 100-fold change in odor concentration, apparently degrading the population representation of odor identity. We show that this problem can be resolved by decoding odor identity from a subpopulation of concentration-invariant piriform neurons. These concentration-invariant neurons are overrepresented in piriform cortex but not in olfactory bulb mitral and tufted cells. We therefore propose that distinct perceptual features of odors are encoded in independent subnetworks of neurons in the olfactory cortex. DOI: http://dx.doi.org/10.7554/eLife.26337.001 PMID:28489003

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams.

PubMed

Beetz, M Jerome; Hechavarría, Julio C; Kössl, Manfred

2016-10-27

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical "default mode" that allows selectively focusing on close obstacle even without active attention from the animals.

Cortical neurons of bats respond best to echoes from nearest targets when listening to natural biosonar multi-echo streams

PubMed Central

Beetz, M. Jerome; Hechavarría, Julio C.; Kössl, Manfred

2016-01-01

Bats orientate in darkness by listening to echoes from their biosonar calls, a behaviour known as echolocation. Recent studies showed that cortical neurons respond in a highly selective manner when stimulated with natural echolocation sequences that contain echoes from single targets. However, it remains unknown how cortical neurons process echolocation sequences containing echo information from multiple objects. In the present study, we used echolocation sequences containing echoes from three, two or one object separated in the space depth as stimuli to study neuronal activity in the bat auditory cortex. Neuronal activity was recorded with multi-electrode arrays placed in the dorsal auditory cortex, where neurons tuned to target-distance are found. Our results show that target-distance encoding neurons are mostly selective to echoes coming from the closest object, and that the representation of echo information from distant objects is selectively suppressed. This suppression extends over a large part of the dorsal auditory cortex and may override possible parallel processing of multiple objects. The presented data suggest that global cortical suppression might establish a cortical “default mode” that allows selectively focusing on close obstacle even without active attention from the animals. PMID:27786252

Activation of the Basal Forebrain by the Orexin/Hypocretin Neurons: Orexin International Symposium

PubMed Central

Arrigoni, Elda; Mochizuki, Takatoshi; Scammell, Thomas E.

2010-01-01

The orexin neurons play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurons promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurons may promote arousal by exciting cortically-projecting neurons of the BF. Orexin fibers synapse on BF cholinergic neurons and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurons, induces cortical release of acetylcholine, and promotes wakefulness. The orexin neurons also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurons that project to the cortex. Cholinergic neurons were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurons that project to the cortex seem to comprise at least two populations with some directly excited by orexin that may represent wake-active, GABAergic neurons, whereas others did not respond to orexin but were inhibited by dynorphin and may be sleep-active, GABAergic neurons. This evidence suggests that the BF is a key site through which orexins activate the cortex and promotes behavioral arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. PMID:19723027

Electroencephalogram evidence for the activation of human mirror neuron system during the observation of intransitive shadow and line drawing actions☆

PubMed Central

Zhu, Huaping; Sun, Yaoru; Wang, Fang

2013-01-01

Previous studies have demonstrated that hand shadows may activate the motor cortex associated with the mirror neuron system in human brain. However, there is no evidence of activity of the human mirror neuron system during the observation of intransitive movements by shadows and line drawings of hands. This study examined the suppression of electroencephalography mu waves (8–13 Hz) induced by observation of stimuli in 18 healthy students. Three stimuli were used: real hand actions, hand shadow actions and actions made by line drawings of hands. The results showed significant desynchronization of the mu rhythm (“mu suppression”) across the sensorimotor cortex (recorded at C3, Cz and C4), the frontal cortex (recorded at F3, Fz and F4) and the central and right posterior parietal cortex (recorded at Pz and P4) under all three conditions. Our experimental findings suggest that the observation of “impoverished hand actions”, such as intransitive movements of shadows and line drawings of hands, is able to activate widespread cortical areas related to the putative human mirror neuron system. PMID:25206595

Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex.

PubMed

Zhao, Ruohe; Zhou, Hang; Huang, Lianyan; Xie, Zhongcong; Wang, Jing; Gan, Wen-Biao; Yang, Guang

2018-01-01

The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5) pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.

Motor cortex embeds muscle-like commands in an untangled population response

PubMed Central

Russo, Abigail A.; Bittner, Sean R.; Perkins, Sean M.; Seely, Jeffrey S.; London, Brian M.; Lara, Antonio H.; Miri, Andrew; Marshall, Najja J.; Kohn, Adam; Jessell, Thomas M.; Abbott, Laurence F.; Cunningham, John P.; Churchland, Mark M.

2018-01-01

Summary Primate motor cortex projects to spinal interneurons and motor neurons, suggesting that motor cortex activity may be dominated by muscle-like commands. Extensive observations during reaching lend support to this view, but evidence remains ambiguous and much-debated. To provide a different perspective, we employed a novel behavioral paradigm that affords extensive comparison between time-evolving neural and muscle activity. We found that single motor cortex neurons displayed many muscle-like properties, but the structure of population activity was not muscle-like. Unlike muscle activity, neural activity was structured to avoid ‘tangling’: moments where similar activity patterns led to dissimilar future patterns. Avoidance of tangling was present across tasks and species. Network models revealed a potential reason for this consistent feature: low tangling confers noise robustness. Finally, we were able to predict motor cortex activity from muscle activity alone, by leveraging the hypothesis that muscle-like commands are embedded in additional structure that yields low tangling. PMID:29398358

Cognitive Control Signals in Posterior Cingulate Cortex

PubMed Central

Hayden, Benjamin Y.; Smith, David V.; Platt, Michael L.

2010-01-01

Efficiently shifting between tasks is a central function of cognitive control. The role of the default network – a constellation of areas with high baseline activity that declines during task performance – in cognitive control remains poorly understood. We hypothesized that task switching demands cognitive control to shift the balance of processing toward the external world, and therefore predicted that switching between the two tasks would require suppression of activity of neurons within the posterior cingulate cortex (CGp). To test this idea, we recorded the activity of single neurons in CGp, a central node in the default network, in monkeys performing two interleaved tasks. As predicted, we found that basal levels of neuronal activity were reduced following a switch from one task to another and gradually returned to pre-switch baseline on subsequent trials. We failed to observe these effects in lateral intraparietal cortex, part of the dorsal fronto-parietal cortical attention network directly connected to CGp. These findings indicate that suppression of neuronal activity in CGp facilitates cognitive control, and suggest that activity in the default network reflects processes that directly compete with control processes elsewhere in the brain. PMID:21160560

Neuronal population coding of perceived and memorized visual features in the lateral prefrontal cortex

PubMed Central

Mendoza-Halliday, Diego; Martinez-Trujillo, Julio C.

2017-01-01

The primate lateral prefrontal cortex (LPFC) encodes visual stimulus features while they are perceived and while they are maintained in working memory. However, it remains unclear whether perceived and memorized features are encoded by the same or different neurons and population activity patterns. Here we record LPFC neuronal activity while monkeys perceive the motion direction of a stimulus that remains visually available, or memorize the direction if the stimulus disappears. We find neurons with a wide variety of combinations of coding strength for perceived and memorized directions: some neurons encode both to similar degrees while others preferentially or exclusively encode either one. Reading out the combined activity of all neurons, a machine-learning algorithm reliably decode the motion direction and determine whether it is perceived or memorized. Our results indicate that a functionally diverse population of LPFC neurons provides a substrate for discriminating between perceptual and mnemonic representations of visual features. PMID:28569756

Remapping of border ownership in the visual cortex.

PubMed

O'Herron, Philip; von der Heydt, Rüdiger

2013-01-30

We see objects as having continuity although the retinal image changes frequently. How such continuity is achieved is hard to understand, because neurons in the visual cortex have small receptive fields that are fixed on the retina, which means that a different set of neurons is activated every time the eyes move. Neurons in areas V1 and V2 of the visual cortex signal the local features that are currently in their receptive fields and do not show "remapping" when the image moves. However, subsets of neurons in these areas also carry information about global aspects, such as figure-ground organization. Here we performed experiments to find out whether figure-ground organization is remapped. We recorded single neurons in macaque V1 and V2 in which figure-ground organization is represented by assignment of contours to regions (border ownership). We found previously that border-ownership signals persist when a figure edge is switched to an ambiguous edge by removing the context. We now used this paradigm to see whether border ownership transfers when the ambiguous edge is moved across the retina. In the new position, the edge activated a different set of neurons at a different location in cortex. We found that border ownership was transferred to the newly activated neurons. The transfer occurred whether the edge was moved by a saccade or by moving the visual display. Thus, although the contours are coded in retinal coordinates, their assignment to objects is maintained across movements of the retinal image.

Stimulus-related activity during conditional associations in monkey perirhinal cortex neurons depends on upcoming reward outcome.

PubMed

Ohyama, Kaoru; Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Shidara, Munetaka; Sato, Chikara

2012-11-28

Acquiring the significance of events based on reward-related information is critical for animals to survive and to conduct social activities. The importance of the perirhinal cortex for reward-related information processing has been suggested. To examine whether or not neurons in this cortex represent reward information flexibly when a visual stimulus indicates either a rewarded or unrewarded outcome, neuronal activity in the macaque perirhinal cortex was examined using a conditional-association cued-reward task. The task design allowed us to study how the neuronal responses depended on the animal's prediction of whether it would or would not be rewarded. Two visual stimuli, a color stimulus as Cue1 followed by a pattern stimulus as Cue2, were sequentially presented. Each pattern stimulus was conditionally associated with both rewarded and unrewarded outcomes depending on the preceding color stimulus. We found an activity depending upon the two reward conditions during Cue2, i.e., pattern stimulus presentation. The response appeared after the response dependent upon the image identity of Cue2. The response delineating a specific cue sequence also appeared between the responses dependent upon the identity of Cue2 and reward conditions. Thus, when Cue1 sets the context for whether or not Cue2 indicates a reward, this region represents the meaning of Cue2, i.e., the reward conditions, independent of the identity of Cue2. These results suggest that neurons in the perirhinal cortex do more than associate a single stimulus with a reward to achieve flexible representations of reward information.

Neural Population Dynamics during Reaching Are Better Explained by a Dynamical System than Representational Tuning

PubMed Central

Dann, Benjamin

2016-01-01

Recent models of movement generation in motor cortex have sought to explain neural activity not as a function of movement parameters, known as representational models, but as a dynamical system acting at the level of the population. Despite evidence supporting this framework, the evaluation of representational models and their integration with dynamical systems is incomplete in the literature. Using a representational velocity-tuning based simulation of center-out reaching, we show that incorporating variable latency offsets between neural activity and kinematics is sufficient to generate rotational dynamics at the level of neural populations, a phenomenon observed in motor cortex. However, we developed a covariance-matched permutation test (CMPT) that reassigns neural data between task conditions independently for each neuron while maintaining overall neuron-to-neuron relationships, revealing that rotations based on the representational model did not uniquely depend on the underlying condition structure. In contrast, rotations based on either a dynamical model or motor cortex data depend on this relationship, providing evidence that the dynamical model more readily explains motor cortex activity. Importantly, implementing a recurrent neural network we demonstrate that both representational tuning properties and rotational dynamics emerge, providing evidence that a dynamical system can reproduce previous findings of representational tuning. Finally, using motor cortex data in combination with the CMPT, we show that results based on small numbers of neurons or conditions should be interpreted cautiously, potentially informing future experimental design. Together, our findings reinforce the view that representational models lack the explanatory power to describe complex aspects of single neuron and population level activity. PMID:27814352

Neural Population Dynamics during Reaching Are Better Explained by a Dynamical System than Representational Tuning.

PubMed

Michaels, Jonathan A; Dann, Benjamin; Scherberger, Hansjörg

2016-11-01

Recent models of movement generation in motor cortex have sought to explain neural activity not as a function of movement parameters, known as representational models, but as a dynamical system acting at the level of the population. Despite evidence supporting this framework, the evaluation of representational models and their integration with dynamical systems is incomplete in the literature. Using a representational velocity-tuning based simulation of center-out reaching, we show that incorporating variable latency offsets between neural activity and kinematics is sufficient to generate rotational dynamics at the level of neural populations, a phenomenon observed in motor cortex. However, we developed a covariance-matched permutation test (CMPT) that reassigns neural data between task conditions independently for each neuron while maintaining overall neuron-to-neuron relationships, revealing that rotations based on the representational model did not uniquely depend on the underlying condition structure. In contrast, rotations based on either a dynamical model or motor cortex data depend on this relationship, providing evidence that the dynamical model more readily explains motor cortex activity. Importantly, implementing a recurrent neural network we demonstrate that both representational tuning properties and rotational dynamics emerge, providing evidence that a dynamical system can reproduce previous findings of representational tuning. Finally, using motor cortex data in combination with the CMPT, we show that results based on small numbers of neurons or conditions should be interpreted cautiously, potentially informing future experimental design. Together, our findings reinforce the view that representational models lack the explanatory power to describe complex aspects of single neuron and population level activity.

Persistently active neurons in human medial frontal and medial temporal lobe support working memory

PubMed Central

Kamiński, J; Sullivan, S; Chung, JM; Ross, IB; Mamelak, AN; Rutishauser, U

2017-01-01

Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and the medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors, and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance. PMID:28218914

Contributions of diverse excitatory and inhibitory neurons to recurrent network activity in cerebral cortex.

PubMed

Neske, Garrett T; Patrick, Saundra L; Connors, Barry W

2015-01-21

The recurrent synaptic architecture of neocortex allows for self-generated network activity. One form of such activity is the Up state, in which neurons transiently receive barrages of excitatory and inhibitory synaptic inputs that depolarize many neurons to spike threshold before returning to a relatively quiescent Down state. The extent to which different cell types participate in Up states is still unclear. Inhibitory interneurons have particularly diverse intrinsic properties and synaptic connections with the local network, suggesting that different interneurons might play different roles in activated network states. We have studied the firing, subthreshold behavior, and synaptic conductances of identified cell types during Up and Down states in layers 5 and 2/3 in mouse barrel cortex in vitro. We recorded from pyramidal cells and interneurons expressing parvalbumin (PV), somatostatin (SOM), vasoactive intestinal peptide (VIP), or neuropeptide Y. PV cells were the most active interneuron subtype during the Up state, yet the other subtypes also received substantial synaptic conductances and often generated spikes. In all cell types except PV cells, the beginning of the Up state was dominated by synaptic inhibition, which decreased thereafter; excitation was more persistent, suggesting that inhibition is not the dominant force in terminating Up states. Compared with barrel cortex, SOM and VIP cells were much less active in entorhinal cortex during Up states. Our results provide a measure of functional connectivity of various neuron types in barrel cortex and suggest differential roles for interneuron types in the generation and control of persistent network activity. Copyright © 2015 the authors 0270-6474/15/351089-17$15.00/0.

State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats.

PubMed

Brazhnik, Elena; Cruz, Ana V; Avila, Irene; Wahba, Marian I; Novikov, Nikolay; Ilieva, Neda M; McCoy, Alex J; Gerber, Colin; Walters, Judith R

2012-06-06

Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.

Optogenetic and pharmacological suppression of spatial clusters of face neurons reveal their causal role in face gender discrimination.

PubMed

Afraz, Arash; Boyden, Edward S; DiCarlo, James J

2015-05-26

Neurons that respond more to images of faces over nonface objects were identified in the inferior temporal (IT) cortex of primates three decades ago. Although it is hypothesized that perceptual discrimination between faces depends on the neural activity of IT subregions enriched with "face neurons," such a causal link has not been directly established. Here, using optogenetic and pharmacological methods, we reversibly suppressed the neural activity in small subregions of IT cortex of macaque monkeys performing a facial gender-discrimination task. Each type of intervention independently demonstrated that suppression of IT subregions enriched in face neurons induced a contralateral deficit in face gender-discrimination behavior. The same neural suppression of other IT subregions produced no detectable change in behavior. These results establish a causal link between the neural activity in IT face neuron subregions and face gender-discrimination behavior. Also, the demonstration that brief neural suppression of specific spatial subregions of IT induces behavioral effects opens the door for applying the technical advantages of optogenetics to a systematic attack on the causal relationship between IT cortex and high-level visual perception.

Sensory nerve crush and regeneration and the receptive fields and response properties of neurons in the primary somatosensory cerebral cortex of cats.

PubMed

Brandenberg, G A; Mann, M D

1989-03-01

Extracellular recordings were made of activity evoked in neurons of the forepaw focus of somatosensory cerebral cortex by electrical stimulation of each paw in control cats and cats that had undergone crush injury of all cutaneous sensory nerves to the contralateral forepaw 31 to 63 days previously. Neurons responding only to stimulation of the contralateral forepaw were classified as sa; neurons responding to stimulation of both forepaws were classified as sb; neurons responding to stimulation of both contralateral paws were classified as sc; and neurons responding to stimulation of at least three paws were classified as m. The ratio sa:sb:sc:m neurons was 46:3:0:0 in control cats and 104:15:3:26 in cats that had undergone nerve crush 1-2 months prior to study. sa neurons from experimental cats had depth distributions similar to those in controls and responded to contralateral forepaw stimulation with more spikes per discharge, longer latency, and higher threshold than sa neurons in control cats. m neurons from experimental cats were distributed deeper in the cortex than sa neurons, and, when compared to experimental sa neurons, they responded with longer latency and poorer frequency-following ability; however, the number of spikes per discharge and threshold were not significantly different. The appearance of wide-field neurons in this tissue may be explained in terms of strengthening of previously sub-threshold inputs to neurons in the somatosensory system. If the neurons in sensory cortex play a requisite role in cutaneous sensations and if changes similar to those reported here occur and persist in human cortex after nerve crush, then "complete" recovery of sensation in such patients may occur against a background of changed cortical neuronal responsiveness.

Sparse orthogonal population representation of spatial context in the retrosplenial cortex.

PubMed

Mao, Dun; Kandler, Steffen; McNaughton, Bruce L; Bonin, Vincent

2017-08-15

Sparse orthogonal coding is a key feature of hippocampal neural activity, which is believed to increase episodic memory capacity and to assist in navigation. Some retrosplenial cortex (RSC) neurons convey distributed spatial and navigational signals, but place-field representations such as observed in the hippocampus have not been reported. Combining cellular Ca 2+ imaging in RSC of mice with a head-fixed locomotion assay, we identified a population of RSC neurons, located predominantly in superficial layers, whose ensemble activity closely resembles that of hippocampal CA1 place cells during the same task. Like CA1 place cells, these RSC neurons fire in sequences during movement, and show narrowly tuned firing fields that form a sparse, orthogonal code correlated with location. RSC 'place' cell activity is robust to environmental manipulations, showing partial remapping similar to that observed in CA1. This population code for spatial context may assist the RSC in its role in memory and/or navigation.Neurons in the retrosplenial cortex (RSC) encode spatial and navigational signals. Here the authors use calcium imaging to show that, similar to the hippocampus, RSC neurons also encode place cell-like activity in a sparse orthogonal representation, partially anchored to the allocentric cues on the linear track.

Spatial attention increases high-frequency gamma synchronisation in human medial visual cortex.

PubMed

Koelewijn, Loes; Rich, Anina N; Muthukumaraswamy, Suresh D; Singh, Krish D

2013-10-01

Visual information processing involves the integration of stimulus and goal-driven information, requiring neuronal communication. Gamma synchronisation is linked to neuronal communication, and is known to be modulated in visual cortex both by stimulus properties and voluntarily-directed attention. Stimulus-driven modulations of gamma activity are particularly associated with early visual areas such as V1, whereas attentional effects are generally localised to higher visual areas such as V4. The absence of a gamma increase in early visual cortex is at odds with robust attentional enhancements found with other measures of neuronal activity in this area. Here we used magnetoencephalography (MEG) to explore the effect of spatial attention on gamma activity in human early visual cortex using a highly effective gamma-inducing stimulus and strong attentional manipulation. In separate blocks, subjects tracked either a parafoveal grating patch that induced gamma activity in contralateral medial visual cortex, or a small line at fixation, effectively attending away from the gamma-inducing grating. Both items were always present, but rotated unpredictably and independently of each other. The rotating grating induced gamma synchronisation in medial visual cortex at 30-70 Hz, and in lateral visual cortex at 60-90 Hz, regardless of whether it was attended. Directing spatial attention to the grating increased gamma synchronisation in medial visual cortex, but only at 60-90 Hz. These results suggest that the generally found increase in gamma activity by spatial attention can be localised to early visual cortex in humans, and that stimulus and goal-driven modulations may be mediated at different frequencies within the gamma range. Copyright © 2013 Elsevier Inc. All rights reserved.

Auditory cortex of newborn bats is prewired for echolocation.

PubMed

Kössl, Manfred; Voss, Cornelia; Mora, Emanuel C; Macias, Silvio; Foeller, Elisabeth; Vater, Marianne

2012-04-10

Neuronal computation of object distance from echo delay is an essential task that echolocating bats must master for spatial orientation and the capture of prey. In the dorsal auditory cortex of bats, neurons specifically respond to combinations of short frequency-modulated components of emitted call and delayed echo. These delay-tuned neurons are thought to serve in target range calculation. It is unknown whether neuronal correlates of active space perception are established by experience-dependent plasticity or by innate mechanisms. Here we demonstrate that in the first postnatal week, before onset of echolocation and flight, dorsal auditory cortex already contains functional circuits that calculate distance from the temporal separation of a simulated pulse and echo. This innate cortical implementation of a purely computational processing mechanism for sonar ranging should enhance survival of juvenile bats when they first engage in active echolocation behaviour and flight.

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

PubMed

Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

2016-03-01

Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of patients with amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability.

PubMed

Ziminski, Joseph J; Hessler, Sabine; Margetts-Smith, Gabriella; Sieburg, Meike C; Crombag, Hans S; Koya, Eisuke

2017-03-22

Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFP+ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFP+ neurons were more excitable than surrounding GFP- neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell. SIGNIFICANCE STATEMENT Sparsely distributed sets of neurons called "neuronal ensembles" encode learned associations about food and cues predictive of its availability. Widespread changes in neuronal excitability have been observed in limbic brain areas after associative learning, but little is known about the excitability changes that occur specifically on neuronal ensembles that encode appetitive associations. Here, we reveal that sucrose cue exposure recruited a more excitable ensemble in the nucleus accumbens, but not orbitofrontal cortex, compared with their surrounding neurons. This excitability difference was not observed when the cue's salience was diminished after extinction learning. These novel data provide evidence that the intrinsic excitability of appetitive memory-encoding ensembles is regulated differentially across brain areas and adapts dynamically to changes in associative strength. Copyright © 2017 the authors 0270-6474/17/373160-11$15.00/0.

High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine Receptors in Hemi-Parkinsonian Rats.

PubMed

Chuang, Chi-Fen; Wu, Chen-Wei; Weng, Ying; Hu, Pei-San; Yeh, Shin-Rung; Chang, Yen-Chung

2018-04-30

Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease (PD). Here, we investigated how DBS applied on the subthalamic nucleus (STN) influenced the neural activity in the motor cortex. Rats, which had the midbrain dopaminergic neurons partially depleted unilaterally, called the hemi-Parkinsonian rats, were used as a study model. c-Fos expression in the neurons was used as an indicator of neural activity. Application of high-frequency stimulation (HFS) upon the STN was used to mimic the DBS treatment. The motor cortices in the two hemispheres of hemi-Parkinsonian rats were found to contain unequal densities of c-Fos-positive (Fos+) cells, and STN-HFS rectified this bilateral imbalance. In addition, STN-HFS led to the intense c-Fos expression in a group of motor cortical neurons which exhibited biochemical and anatomical characteristics resembling those of the pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons expressing high levels of c-Fos was significantly reduced by local application of the antagonists of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, gammaaminobutyric acid A (GABAA) receptors and dopamine receptors in the upper layers of the motor cortex. The results indicate that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS trigger the intense expression of c-Fos of the PT neurons. The implications of the results on the cellular mechanism underlying the therapeutic effects of STN-DBS on the movement disorders of PD are also discussed.

Network activity of mirror neurons depends on experience.

PubMed

Ushakov, Vadim L; Kartashov, Sergey I; Zavyalova, Victoria V; Bezverhiy, Denis D; Posichanyuk, Vladimir I; Terentev, Vasliliy N; Anokhin, Konstantin V

2013-03-01

In this work, the investigation of network activity of mirror neurons systems in animal brains depending on experience (existence or absence performance of the shown actions) was carried out. It carried out the research of mirror neurons network in the C57/BL6 line mice in the supervision task of swimming mice-demonstrators in Morris water maze. It showed the presence of mirror neurons systems in the motor cortex M1, M2, cingular cortex, hippocampus in mice groups, having experience of the swimming and without it. The conclusion is drawn about the possibility of the new functional network systems formation by means of mirror neurons systems and the acquisition of new knowledge through supervision by the animals in non-specific tasks.

Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome.

PubMed

Tyzio, Roman; Khalilov, Ilgam; Represa, Alfonso; Crepel, Valerie; Zilberter, Yuri; Rheims, Sylvain; Aniksztejn, Laurent; Cossart, Rosa; Nardou, Romain; Mukhtarov, Marat; Minlebaev, Marat; Epsztein, Jérôme; Milh, Mathieu; Becq, Helene; Jorquera, Isabel; Bulteau, Christine; Fohlen, Martine; Oliver, Viviana; Dulac, Olivier; Dorfmüller, Georg; Delalande, Olivier; Ben-Ari, Yehezkel; Khazipov, Roustem

2009-08-01

The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies. Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery. Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many cells spontaneously fired action potentials at a rate proportional to the level of neuronal depolarization. The reversal potential for GABA-activated currents, assessed by cell-attached single channel recordings, was close to the resting membrane potential. All spontaneously firing neurons recorded in cell-attached mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous epileptiform activity in the form of recurrent population bursts was suppressed by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had little effect on epileptiform activity. SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex.

Functionally Specific Oscillatory Activity Correlates between Visual and Auditory Cortex in the Blind

ERIC Educational Resources Information Center

Schepers, Inga M.; Hipp, Joerg F.; Schneider, Till R.; Roder, Brigitte; Engel, Andreas K.

2012-01-01

Many studies have shown that the visual cortex of blind humans is activated in non-visual tasks. However, the electrophysiological signals underlying this cross-modal plasticity are largely unknown. Here, we characterize the neuronal population activity in the visual and auditory cortex of congenitally blind humans and sighted controls in a…

Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons

PubMed Central

Aton, Sara J.; Broussard, Christopher; Dumoulin, Michelle; Seibt, Julie; Watson, Adam; Coleman, Tammi; Frank, Marcos G.

2013-01-01

Ocular dominance plasticity in the developing primary visual cortex is initiated by monocular deprivation (MD) and consolidated during subsequent sleep. To clarify how visual experience and sleep affect neuronal activity and plasticity, we continuously recorded extragranular visual cortex fast-spiking (FS) interneurons and putative principal (i.e., excitatory) neurons in freely behaving cats across periods of waking MD and post-MD sleep. Consistent with previous reports in mice, MD induces two related changes in FS interneurons: a response shift in favor of the closed eye and depression of firing. Spike-timing–dependent depression of open-eye–biased principal neuron inputs to FS interneurons may mediate these effects. During post-MD nonrapid eye movement sleep, principal neuron firing increases and becomes more phase-locked to slow wave and spindle oscillations. Ocular dominance (OD) shifts in favor of open-eye stimulation—evident only after post-MD sleep—are proportional to MD-induced changes in FS interneuron activity and to subsequent sleep-associated changes in principal neuron activity. OD shifts are greatest in principal neurons that fire 40–300 ms after neighboring FS interneurons during post-MD slow waves. Based on these data, we propose that MD-induced changes in FS interneurons play an instructive role in ocular dominance plasticity, causing disinhibition among open-eye–biased principal neurons, which drive plasticity throughout the visual cortex during subsequent sleep. PMID:23300282

Characterization of postsynaptic calcium signals in the pyramidal neurons of anterior cingulate cortex

PubMed Central

Li, Xu-Hui; Song, Qian; Chen, Tao; Zhuo, Min

2017-01-01

Calcium signaling is critical for synaptic transmission and plasticity. N-methyl-D-aspartic acid (NMDA) receptors play a key role in synaptic potentiation in the anterior cingulate cortex. Most previous studies of calcium signaling focus on hippocampal neurons, little is known about the activity-induced calcium signals in the anterior cingulate cortex. In the present study, we show that NMDA receptor-mediated postsynaptic calcium signals induced by different synaptic stimulation in anterior cingulate cortex pyramidal neurons. Single and multi-action potentials evoked significant suprathreshold Ca2+ increases in somas and spines. Both NMDA receptors and voltage-gated calcium channels contributed to this increase. Postsynaptic Ca2+signals were induced by puff-application of glutamate, and a NMDA receptor antagonist AP5 blocked these signals in both somas and spines. Finally, long-term potentiation inducing protocols triggered postsynaptic Ca2+ influx, and these influx were NMDA receptor dependent. Our results provide the first study of calcium signals in the anterior cingulate cortex and demonstrate that NMDA receptors play important roles in postsynaptic calcium signals in anterior cingulate cortex pyramidal neurons. PMID:28726541

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis.

PubMed

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.

GABAergic neurons in ferret visual cortex participate in functionally specific networks

PubMed Central

Wilson, Daniel E.; Smith, Gordon B.; Jacob, Amanda; Walker, Theo; Dimidschstein, Jordane; Fishell, Gord J.; Fitzpatrick, David

2017-01-01

Summary Functional circuits in the visual cortex require the coordinated activity of excitatory and inhibitory neurons. Molecular genetic approaches in the mouse have led to the ‘local nonspecific pooling principle’ of inhibitory connectivity, in which inhibitory neurons are untuned for stimulus features due to the random pooling of local inputs. However, it remains unclear whether this principle generalizes to species with a columnar organization of feature selectivity such as carnivores, primates, and humans. Here we use virally-mediated GABAergic-specific GCaMP6f expression to demonstrate that inhibitory neurons in ferret visual cortex respond robustly and selectively to oriented stimuli. We find that the tuning of inhibitory neurons is inconsistent with the local non-specific pooling of excitatory inputs, and that inhibitory neurons exhibit orientation-specific noise correlations with local and distant excitatory neurons. These findings challenge the generality of the non-specific pooling principle for inhibitory neurons, suggesting different rules for functional excitatory-inhibitory interactions in non-murine species. PMID:28279352

Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis

PubMed Central

Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

2007-01-01

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1-deficient mice (Ppt1−/−) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression, but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1−/− mice, revealing the thalamus as an important early focus of INCL pathogenesis. PMID:17046272

Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories

PubMed Central

Warren, Brandon L.; Mendoza, Michael P.; Cruz, Fabio C.; Leao, Rodrigo M.; Caprioli, Daniele; Rubio, F. Javier; Whitaker, Leslie R.; McPherson, Kylie B.; Bossert, Jennifer M.; Shaham, Yavin

2016-01-01

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in “neuronal ensembles.” Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area. SIGNIFICANCE STATEMENT A current popular hypothesis is that neuronal ensembles in different prefrontal cortex areas control reward-associated versus extinction-associated memories: the dorsal medial prefrontal cortex (mPFC) promotes reward seeking, whereas the ventral mPFC inhibits reward seeking. In this paper, we use the Daun02 chemogenetic inactivation procedure to demonstrate that Fos-expressing neuronal ensembles mediating both food reward and extinction memories intermingle within the same ventral mPFC area. PMID:27335401

Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories.

PubMed

Warren, Brandon L; Mendoza, Michael P; Cruz, Fabio C; Leao, Rodrigo M; Caprioli, Daniele; Rubio, F Javier; Whitaker, Leslie R; McPherson, Kylie B; Bossert, Jennifer M; Shaham, Yavin; Hope, Bruce T

2016-06-22

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in "neuronal ensembles." Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area. A current popular hypothesis is that neuronal ensembles in different prefrontal cortex areas control reward-associated versus extinction-associated memories: the dorsal medial prefrontal cortex (mPFC) promotes reward seeking, whereas the ventral mPFC inhibits reward seeking. In this paper, we use the Daun02 chemogenetic inactivation procedure to demonstrate that Fos-expressing neuronal ensembles mediating both food reward and extinction memories intermingle within the same ventral mPFC area. Copyright © 2016 the authors 0270-6474/16/366691-13$15.00/0.

Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure.

PubMed

Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo; Rydbirk, Rasmus; Olesen, Mikkel Vestergaard; Hay-Schmidt, Anders; Pakkenberg, Bente; Aznar, Susana

2017-05-30

The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT 2A receptor (5-HT 2A R) dependent. Here, we further investigated how blockade of 5-HT 2A Rs in mice exposed to a novel open-field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact of 5-HT 2A R blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results support a role of 5-HT 2A R activation in modulating mPFC and BLA activation during exposure to a novel environment, which may be interrelated. Conversely, 5-HT 2A R blockade does not seem to affect the amygdala-striatal projection. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuronal coding of implicit emotion categories in the subcallosal cortex in patients with depression.

PubMed

Laxton, Adrian W; Neimat, Joseph S; Davis, Karen D; Womelsdorf, Thilo; Hutchison, William D; Dostrovsky, Jonathan O; Hamani, Clement; Mayberg, Helen S; Lozano, Andres M

2013-11-15

The subcallosal cingulate and adjacent ventromedial prefrontal cortex (collectively referred to here as the subcallosal cortex or SCC) have been identified as key brain areas in emotional processing. The SCC's role in affective valuation as well as severe mood and motivational disturbances, such as major depression, has been largely inferred from measures of neuronal population activity using functional neuroimaging. On the basis of imaging studies, it is unclear whether the SCC predominantly processes 1) negatively valenced affective content, 2) affective arousal, or 3) category-specific affective information. To clarify these putative functional roles of the SCC, we measured single neuron activity in the SCC of 15 human subjects undergoing deep brain stimulation for depression while they viewed emotionally evocative images grouped into categories that varied in emotional valence (pleasantness) and arousal. We found that the majority of responsive neurons were modulated by specific emotion categories, rather than by valence or arousal alone. Moreover, although these emotion-category-specific neurons responded to both positive and negative emotion categories, a significant majority were selective for negatively valenced emotional content. These findings reveal that single SCC neuron activity reflects the automatic valuational processing and implicit emotion categorization of visual stimuli. Furthermore, because of the predominance of neuronal signals in SCC conveying negative affective valuations and the increased activity in this region among depressed people, the effectiveness of depression therapies that alter SCC neuronal activity may relate to the down-regulation of a previously negative emotional processing bias. © 2013 Society of Biological Psychiatry.

Neuronal correlate of pictorial short-term memory in the primate temporal cortexYasushi Miyashita

NASA Astrophysics Data System (ADS)

Miyashita, Yasushi; Chang, Han Soo

1988-01-01

It has been proposed that visual-memory traces are located in the temporal lobes of the cerebral cortex, as electric stimulation of this area in humans results in recall of imagery1. Lesions in this area also affect recognition of an object after a delay in both humans2,3 and monkeys4-7 indicating a role in short-term memory of images8. Single-unit recordings from the temporal cortex have shown that some neurons continue to fire when one of two or four colours are to be remembered temporarily9. But neuronal responses selective to specific complex objects10-18 , including hands10,13 and faces13,16,17, cease soon after the offset of stimulus presentation10-18. These results led to the question of whether any of these neurons could serve the memory of complex objects. We report here a group of shape-selective neurons in an anterior ventral part of the temporal cortex of monkeys that exhibited sustained activity during the delay period of a visual short-term memory task. The activity was highly selective for the pictorial information to be memorized and was independent of the physical attributes such as size, orientation, colour or position of the object. These observations show that the delay activity represents the short-term memory of the categorized percept of a picture.

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro

PubMed Central

Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P. C.; Livesey, Frederick J.

2015-01-01

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. PMID:26395144

Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

PubMed

Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

2015-09-15

A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (<10) of presynaptic inputs, whereas a small set of hub-like neurons have large numbers of synaptic connections (>40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. © 2015. Published by The Company of Biologists Ltd.

State-Dependent Spike and Local Field Synchronization between Motor Cortex and Substantia Nigra in Hemiparkinsonian Rats

PubMed Central

Brazhnik, Elena; Cruz, Ana V.; Avila, Irene; Wahba, Marian I.; Novikov, Nikolay; Ilieva, Neda M.; McCoy, Alex J.; Gerber, Colin; Walters, Judith. R.

2012-01-01

Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of Parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, seven days after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8–25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25–40 Hz band with a peak frequency at 30–35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25–40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity. PMID:22674263

Neuroimaging and Neuromodulation: Complementary Approaches for Identifying the Neuronal Correlates of Tinnitus

PubMed Central

Langguth, Berthold; Schecklmann, Martin; Lehner, Astrid; Landgrebe, Michael; Poeppl, Timm Benjamin; Kreuzer, Peter Michal; Schlee, Winfried; Weisz, Nathan; Vanneste, Sven; De Ridder, Dirk

2012-01-01

An inherent limitation of functional imaging studies is their correlational approach. More information about critical contributions of specific brain regions can be gained by focal transient perturbation of neural activity in specific regions with non-invasive focal brain stimulation methods. Functional imaging studies have revealed that tinnitus is related to alterations in neuronal activity of central auditory pathways. Modulation of neuronal activity in auditory cortical areas by repetitive transcranial magnetic stimulation (rTMS) can reduce tinnitus loudness and, if applied repeatedly, exerts therapeutic effects, confirming the relevance of auditory cortex activation for tinnitus generation and persistence. Measurements of oscillatory brain activity before and after rTMS demonstrate that the same stimulation protocol has different effects on brain activity in different patients, presumably related to interindividual differences in baseline activity in the clinically heterogeneous study cohort. In addition to alterations in auditory pathways, imaging techniques also indicate the involvement of non-auditory brain areas, such as the fronto-parietal “awareness” network and the non-tinnitus-specific distress network consisting of the anterior cingulate cortex, anterior insula, and amygdale. Involvement of the hippocampus and the parahippocampal region putatively reflects the relevance of memory mechanisms in the persistence of the phantom percept and the associated distress. Preliminary studies targeting the dorsolateral prefrontal cortex, the dorsal anterior cingulate cortex, and the parietal cortex with rTMS and with transcranial direct current stimulation confirm the relevance of the mentioned non-auditory networks. Available data indicate the important value added by brain stimulation as a complementary approach to neuroimaging for identifying the neuronal correlates of the various clinical aspects of tinnitus. PMID:22509155

Monkey prefrontal neurons during Sternberg task performance: full contents of working memory or most recent item?

PubMed

Konecky, R O; Smith, M A; Olson, C R

2017-06-01

To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or represented within the prefrontal cortex in a cryptic code. Copyright © 2017 the American Physiological Society.

Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive abilities and is modulated by working memory training

PubMed Central

Wass, Christopher; Pizzo, Alessandro; Sauce, Bruno; Kawasumi, Yushi; Sturzoiu, Tudor; Ree, Fred; Otto, Tim; Matzel, Louis D.

2013-01-01

A common source of variance (i.e., “general intelligence”) underlies an individual's performance across diverse tests of cognitive ability, and evidence indicates that the processing efficacy of working memory may serve as one such source of common variance. One component of working memory, selective attention, has been reported to co-vary with general intelligence, and dopamine D1 signaling in prefrontal cortex can modulate attentional abilities. Based on their aggregate performance across five diverse tests of learning, here we characterized the general cognitive ability (GCA) of CD-1 outbred mice. In response to a D1 agonist (SKF82958, 1 mg/kg), we then assessed the relationship between GCA and activation of D1 receptor (D1R)-containing neurons in the prelimbic region of the medial prefrontal cortex, the agranular insular cortex, and the dorsomedial striatum. Increased activation of D1R-containing neurons in the prelimbic cortex (but not the agranular insular cortex or dorsomedial striatum) was observed in animals of high GCA relative to those of low GCA (quantified by c-Fos activation in response to the D1 agonist). However, a Western blot analysis revealed no differences in the density of D1Rs in the prelimbic cortex between animals of high and low GCA. Last, it was observed that working memory training promoted an increase in animals’ GCA and enhanced D1R-mediated neuronal activation in the prelimbic cortex. These results suggest that the sensitivity (but not density) of D1Rs in the prelimbic cortex may both regulate GCA and be a target for working memory training. PMID:24129098

Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive abilities and is modulated by working memory training.

PubMed

Wass, Christopher; Pizzo, Alessandro; Sauce, Bruno; Kawasumi, Yushi; Sturzoiu, Tudor; Ree, Fred; Otto, Tim; Matzel, Louis D

2013-10-15

A common source of variance (i.e., "general intelligence") underlies an individual's performance across diverse tests of cognitive ability, and evidence indicates that the processing efficacy of working memory may serve as one such source of common variance. One component of working memory, selective attention, has been reported to co-vary with general intelligence, and dopamine D1 signaling in prefrontal cortex can modulate attentional abilities. Based on their aggregate performance across five diverse tests of learning, here we characterized the general cognitive ability (GCA) of CD-1 outbred mice. In response to a D1 agonist (SKF82958, 1 mg/kg), we then assessed the relationship between GCA and activation of D1 receptor (D1R)-containing neurons in the prelimbic region of the medial prefrontal cortex, the agranular insular cortex, and the dorsomedial striatum. Increased activation of D1R-containing neurons in the prelimbic cortex (but not the agranular insular cortex or dorsomedial striatum) was observed in animals of high GCA relative to those of low GCA (quantified by c-Fos activation in response to the D1 agonist). However, a Western blot analysis revealed no differences in the density of D1Rs in the prelimbic cortex between animals of high and low GCA. Last, it was observed that working memory training promoted an increase in animals' GCA and enhanced D1R-mediated neuronal activation in the prelimbic cortex. These results suggest that the sensitivity (but not density) of D1Rs in the prelimbic cortex may both regulate GCA and be a target for working memory training.

Social Context-Dependent Activity in Marmoset Frontal Cortex Populations during Natural Conversations

PubMed Central

de la Mothe, Lisa; Miller, Cory T.

2017-01-01

Communication is an inherently interactive process that weaves together the fabric of both human and nonhuman primate societies. To investigate the properties of the primate brain during active social signaling, we recorded the responses of frontal cortex neurons as freely moving marmosets engaged in conversational exchanges with a visually occluded virtual marmoset. We found that small changes in firing rate (∼1 Hz) occurred across a broadly distributed population of frontal cortex neurons when marmosets heard a conspecific vocalization, and that these changes corresponded to subjects' likelihood of producing or withholding a vocal reply. Although the contributions of individual neurons were relatively small, large populations of neurons were able to clearly distinguish between these social contexts. Most significantly, this social context-dependent change in firing rate was evident even before subjects heard the vocalization, indicating that the probability of a conversational exchange was determined by the state of the frontal cortex at the time a vocalization was heard, and not by a decision driven by acoustic characteristics of the vocalization. We found that changes in neural activity scaled with the length of the conversation, with greater changes in firing rate evident for longer conversations. These data reveal specific and important facets of this neural activity that constrain its possible roles in active social signaling, and we hypothesize that the close coupling between frontal cortex activity and this natural, active primate social-signaling behavior facilitates social-monitoring mechanisms critical to conversational exchanges. SIGNIFICANCE STATEMENT We provide evidence for a novel pattern of neural activity in the frontal cortex of freely moving, naturally behaving, marmoset monkeys that may facilitate natural primate conversations. We discovered small (∼1 Hz), but reliable, changes in neural activity that occurred before marmosets even heard a conspecific vocalization that, as a population, almost perfectly predicted whether subjects would produce a vocalization in response. The change in the state of the frontal cortex persisted throughout the conversation and its magnitude scaled linearly with the length of the interaction. We hypothesize that this social context-dependent change in frontal cortex activity is supported by several mechanisms, such as social arousal and attention, and facilitates social monitoring critical for vocal coordination characteristic of human and nonhuman primate conversations. PMID:28630255

Selective functional interactions between excitatory and inhibitory cortical neurons and differential contribution to persistent activity of the slow oscillation.

PubMed

Tahvildari, Babak; Wölfel, Markus; Duque, Alvaro; McCormick, David A

2012-08-29

The neocortex depends upon a relative balance of recurrent excitation and inhibition for its operation. During spontaneous Up states, cortical pyramidal cells receive proportional barrages of excitatory and inhibitory synaptic potentials. Many of these synaptic potentials arise from the activity of nearby neurons, although the identity of these cells is relatively unknown, especially for those underlying the generation of inhibitory synaptic events. To address these fundamental questions, we developed an in vitro submerged slice preparation of the mouse entorhinal cortex that generates robust and regular spontaneous recurrent network activity in the form of the slow oscillation. By performing whole-cell recordings from multiple cell types identified with green fluorescent protein expression and electrophysiological and/or morphological properties, we show that distinct functional subpopulations of neurons exist in the entorhinal cortex, with large variations in contribution to the generation of balanced excitation and inhibition during the slow oscillation. The most active neurons during the slow oscillation are excitatory pyramidal and inhibitory fast spiking interneurons, receiving robust barrages of both excitatory and inhibitory synaptic potentials. Weak action potential activity was observed in stellate excitatory neurons and somatostatin-containing interneurons. In contrast, interneurons containing neuropeptide Y, vasoactive intestinal peptide, or the 5-hydroxytryptamine (serotonin) 3a receptor, were silent. Our data demonstrate remarkable functional specificity in the interactions between different excitatory and inhibitory cortical neuronal subtypes, and suggest that it is the large recurrent interaction between pyramidal neurons and fast spiking interneurons that is responsible for the generation of persistent activity that characterizes the depolarized states of the cortex.

Optogenetic and pharmacological suppression of spatial clusters of face neurons reveal their causal role in face gender discrimination

PubMed Central

Afraz, Arash; Boyden, Edward S.; DiCarlo, James J.

2015-01-01

Neurons that respond more to images of faces over nonface objects were identified in the inferior temporal (IT) cortex of primates three decades ago. Although it is hypothesized that perceptual discrimination between faces depends on the neural activity of IT subregions enriched with “face neurons,” such a causal link has not been directly established. Here, using optogenetic and pharmacological methods, we reversibly suppressed the neural activity in small subregions of IT cortex of macaque monkeys performing a facial gender-discrimination task. Each type of intervention independently demonstrated that suppression of IT subregions enriched in face neurons induced a contralateral deficit in face gender-discrimination behavior. The same neural suppression of other IT subregions produced no detectable change in behavior. These results establish a causal link between the neural activity in IT face neuron subregions and face gender-discrimination behavior. Also, the demonstration that brief neural suppression of specific spatial subregions of IT induces behavioral effects opens the door for applying the technical advantages of optogenetics to a systematic attack on the causal relationship between IT cortex and high-level visual perception. PMID:25953336

Sexual attraction enhances glutamate transmission in mammalian anterior cingulate cortex

PubMed Central

Wu, Long-Jun; Kim, Susan S; Li, Xiangyao; Zhang, Fuxing; Zhuo, Min

2009-01-01

Functional human brain imaging studies have indicated the essential role of cortical regions, such as the anterior cingulate cortex (ACC), in romantic love and sex. However, the neurobiological basis of how the ACC neurons are activated and engaged in sexual attraction remains unknown. Using transgenic mice in which the expression of green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos, we found that ACC pyramidal neurons are activated by sexual attraction. The presynaptic glutamate release to the activated neurons is increased and pharmacological inhibition of neuronal activities in the ACC reduced the interest of male mice to female mice. Our results present direct evidence of the critical role of the ACC in sexual attraction, and long-term increases in glutamate mediated excitatory transmission may contribute to sexual attraction between male and female mice. PMID:19419552

Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons.

PubMed

Shulha, Hennady P; Cheung, Iris; Whittle, Catheryne; Wang, Jie; Virgil, Daniel; Lin, Cong L; Guo, Yin; Lessard, Andree; Akbarian, Schahram; Weng, Zhiping

2012-03-01

Neuronal dysfunction in cerebral cortex and other brain regions could contribute to the cognitive and behavioral defects in autism. To characterize epigenetic signatures of autism in prefrontal cortex neurons. We performed fluorescence-activated sorting and separation of neuronal and nonneuronal nuclei from postmortem prefrontal cortex, digested the chromatin with micrococcal nuclease, and deeply sequenced the DNA from the mononucleosomes with trimethylated H3K4 (H3K4me3), a histone mark associated with transcriptional regulation. Approximately 15 billion base pairs of H3K4me3-enriched sequences were collected from 32 brains. Academic medical center. A total of 16 subjects diagnosed as having autism and 16 control subjects ranging in age from 0.5 to 70 years. Identification of genomic loci showing autism-associated H3K4me3 changes in prefrontal cortex neurons. Subjects with autism showed no evidence for generalized disruption of the developmentally regulated remodeling of the H3K4me3 landscape that defines normal prefrontal cortex neurons in early infancy. However, excess spreading of H3K4me3 from the transcription start sites into downstream gene bodies and upstream promoters was observed specifically in neuronal chromatin from 4 of 16 autism cases but not in controls. Variable subsets of autism cases exhibit altered H3K4me3 peaks at numerous genes regulating neuronal connectivity, social behaviors, and cognition, often in conjunction with altered expression of the corresponding transcripts. Autism-associated H3K4me3 peaks were significantly enriched in genes and loci implicated in neurodevelopmental diseases. Prefrontal cortex neurons from subjects with autism show changes in chromatin structures at hundreds of loci genome-wide, revealing considerable overlap between genetic and epigenetic risk maps of developmental brain disorders.

Temporal filtering of reward signals in the dorsal anterior cingulate cortex during a mixed-strategy game

PubMed Central

Seo, Hyojung; Lee, Daeyeol

2008-01-01

The process of decision making in humans and other animals is adaptive and can be tuned through experience so as to optimize the outcomes of their choices in a dynamic environment. Previous studies have demonstrated that the anterior cingulate cortex plays an important role in updating the animal’s behavioral strategies when the action-outcome contingencies change. Moreover, neurons in the anterior cingulate cortex often encode the signals related to expected or actual reward. We investigated whether reward-related activity in the anterior cingulate cortex is affected by the animal’s previous reward history. This was tested in rhesus monkeys trained to make binary choices in a computer-simulated competitive zero-sum game. The animal’s choice behavior was relatively close to the optimal strategy, but also revealed small but systematic biases that are consistent with the use of a reinforcement learning algorithm. In addition, the activity of neurons in the dorsal anterior cingulate cortex that was related to the reward received by the animal in a given trial was often modulated by the rewards in the previous trials. Some of these neurons encoded the rate of rewards in previous trials, whereas others displayed activity modulations more closely related to the reward prediction errors. By contrast, signals related to the animal’s choices were only weakly represented in this cortical area. These results suggest that neurons in the dorsal anterior cingulate cortex might be involved in the subjective evaluation of choice outcomes based on the animal’s reward history. PMID:17670983

Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks.

PubMed

Ebina, Teppei; Masamizu, Yoshito; Tanaka, Yasuhiro R; Watakabe, Akiya; Hirakawa, Reiko; Hirayama, Yuka; Hira, Riichiro; Terada, Shin-Ichiro; Koketsu, Daisuke; Hikosaka, Kazuo; Mizukami, Hiroaki; Nambu, Atsushi; Sasaki, Erika; Yamamori, Tetsuo; Matsuzaki, Masanori

2018-05-14

Two-photon imaging in behaving animals has revealed neuronal activities related to behavioral and cognitive function at single-cell resolution. However, marmosets have posed a challenge due to limited success in training on motor tasks. Here we report the development of protocols to train head-fixed common marmosets to perform upper-limb movement tasks and simultaneously perform two-photon imaging. After 2-5 months of training sessions, head-fixed marmosets can control a manipulandum to move a cursor to a target on a screen. We conduct two-photon calcium imaging of layer 2/3 neurons in the motor cortex during this motor task performance, and detect task-relevant activity from multiple neurons at cellular and subcellular resolutions. In a two-target reaching task, some neurons show direction-selective activity over the training days. In a short-term force-field adaptation task, some neurons change their activity when the force field is on. Two-photon calcium imaging in behaving marmosets may become a fundamental technique for determining the spatial organization of the cortical dynamics underlying action and cognition.

Reward Size Informs Repeat-Switch Decisions and Strongly Modulates the Activity of Neurons in Parietal Cortex

PubMed Central

Kubanek, Jan; Snyder, Lawrence H.

2017-01-01

Abstract Behavior is guided by previous experience. Good, positive outcomes drive a repetition of a previous behavior or choice, whereas poor or bad outcomes lead to an avoidance. How these basic drives are implemented by the brain has been of primary interest to psychology and neuroscience. We engaged animals in a choice task in which the size of a reward outcome strongly governed the animals' subsequent decision whether to repeat or switch the previous choice. We recorded the discharge activity of neurons implicated in reward-based choice in 2 regions of parietal cortex. We found that the tendency to retain previous choice following a large (small) reward was paralleled by a marked decrease (increase) in the activity of parietal neurons. This neural effect is independent of, and of sign opposite to, value-based modulations reported in parietal cortex previously. This effect shares the same basic properties with signals previously reported in the limbic system that detect the size of the recently obtained reward to mediate proper repeat-switch decisions. We conclude that the size of the obtained reward is a decision variable that guides the decision between retaining a choice or switching, and neurons in parietal cortex strongly respond to this novel decision variable. PMID:26491065

Activity propagation in an avian basal ganglia-thalamo-cortical circuit essential for vocal learning

PubMed Central

Kojima, Satoshi; Doupe, Allison J.

2009-01-01

In mammalian basal ganglia-thalamo-cortical circuits, GABAergic pallidal neurons are thought to ‘gate’ or modulate excitation in thalamus with their strong inhibitory inputs, and thus signal to cortex by pausing and permitting thalamic neurons to fire in response to excitatory drive. In contrast, in a homologous circuit specialized for vocal learning in songbirds, evidence suggests that pallidal neurons signal by eliciting postinhibitory rebound spikes in thalamus, which could occur even without any excitatory drive to thalamic neurons. To test whether songbird pallidal neurons can also communicate with thalamus by gating excitatory drive, as well as by postinhibitory rebound, we examined the activity of thalamic relay neurons in response to acute inactivation of the basal ganglia structure Area X; Area X contains the pallidal neurons that project to thalamus. Although inactivation of Area X should eliminate rebound-mediated spiking in thalamus, this manipulation tonically increases the firing rate of thalamic relay neurons, providing evidence that songbird pallidal neurons can gate tonic thalamic excitatory drive. We also found that the increased thalamic activity was fed forward to its target in the avian equivalent of cortex, which includes neurons that project to the vocal premotor area. These data raise the possibility that basal ganglia circuits can signal to cortex through thalamus both by generating postinhibitory rebound and by gating excitatory drive, and may switch between these modes depending on the statistics of pallidal firing. Moreover, these findings provide insight into the strikingly different disruptive effects of basal ganglia and ‘cortical’ lesions on songbird vocal learning. PMID:19369547

Evolution of the dynamic properties of the cortex-basal ganglia network after dopaminergic depletion in rats.

PubMed

Dejean, Cyril; Nadjar, Agnes; Le Moine, Catherine; Bioulac, Bernard; Gross, Christian E; Boraud, Thomas

2012-05-01

It is well established that parkinsonian syndrome is associated with alterations of neuronal activity temporal pattern basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in Parkinson's disease patients as well as animal models such as 6-hydroxydopamine treated rats. We recently demonstrated that this increase in oscillatory synchronization is present during high-voltage spindles (HVS) probably underpinned by the disorganization of cortex-BG interactions. Here we investigated the time course of both oscillatory and motor alterations. For that purpose we performed daily simultaneous recordings of neuronal activity in motor cortex, striatum and substantia nigra pars reticulata (SNr), before and after 6-hydroxydopamine lesion in awake rats. After a brief non-dopamine-specific desynchronization, oscillatory activity first increased during HVS followed by progressive motor impairment and the shortening of SNr activation delay. While the oscillatory firing increase reflects dopaminergic depletion, response alteration in SNr neurons is closely related to motor symptom. Copyright © 2012 Elsevier Inc. All rights reserved.

Somatosensory responses in a human motor cortex

PubMed Central

Donoghue, John P.; Hochberg, Leigh R.

2013-01-01

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. PMID:23343902

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines.

PubMed

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca 2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca 2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca 2+ indicators, we recorded the Ca 2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca 2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines

PubMed Central

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors. PMID:29740289

Voltage Imaging of Waking Mouse Cortex Reveals Emergence of Critical Neuronal Dynamics

PubMed Central

Scott, Gregory; Fagerholm, Erik D.; Mutoh, Hiroki; Leech, Robert; Sharp, David J.; Shew, Woodrow L.

2014-01-01

Complex cognitive processes require neuronal activity to be coordinated across multiple scales, ranging from local microcircuits to cortex-wide networks. However, multiscale cortical dynamics are not well understood because few experimental approaches have provided sufficient support for hypotheses involving multiscale interactions. To address these limitations, we used, in experiments involving mice, genetically encoded voltage indicator imaging, which measures cortex-wide electrical activity at high spatiotemporal resolution. Here we show that, as mice recovered from anesthesia, scale-invariant spatiotemporal patterns of neuronal activity gradually emerge. We show for the first time that this scale-invariant activity spans four orders of magnitude in awake mice. In contrast, we found that the cortical dynamics of anesthetized mice were not scale invariant. Our results bridge empirical evidence from disparate scales and support theoretical predictions that the awake cortex operates in a dynamical regime known as criticality. The criticality hypothesis predicts that small-scale cortical dynamics are governed by the same principles as those governing larger-scale dynamics. Importantly, these scale-invariant principles also optimize certain aspects of information processing. Our results suggest that during the emergence from anesthesia, criticality arises as information processing demands increase. We expect that, as measurement tools advance toward larger scales and greater resolution, the multiscale framework offered by criticality will continue to provide quantitative predictions and insight on how neurons, microcircuits, and large-scale networks are dynamically coordinated in the brain. PMID:25505314

Recruitment of local inhibitory networks by horizontal connections in layer 2/3 of ferret visual cortex.

PubMed

Tucker, Thomas R; Katz, Lawrence C

2003-01-01

To investigate how neurons in cortical layer 2/3 integrate horizontal inputs arising from widely distributed sites, we combined intracellular recording and voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of neuronal activity evoked by electrical stimulation of multiple sites in visual cortex. Individual stimuli evoked characteristic patterns of optical activity, while delivering stimuli at multiple sites generated interacting patterns in the regions of overlap. We observed that neurons in overlapping regions received convergent horizontal activation that generated nonlinear responses due to the emergence of large inhibitory potentials. The results indicate that co-activation of multiple sets of horizontal connections recruit strong inhibition from local inhibitory networks, causing marked deviations from simple linear integration.

Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex

PubMed Central

Nir, Yuval; Mukamel, Roy; Dinstein, Ilan; Privman, Eran; Harel, Michal; Fisch, Lior; Gelbard-Sagiv, Hagar; Kipervasser, Svetlana; Andelman, Fani; Neufeld, Miri Y; Kramer, Uri; Arieli, Amos; Fried, Itzhak; Malach, Rafael

2009-01-01

Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40–100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex. PMID:19160509

Body stability and muscle and motor cortex activity during walking with wide stance

PubMed Central

Farrell, Brad J.; Bulgakova, Margarita A.; Beloozerova, Irina N.; Sirota, Mikhail G.

2014-01-01

Biomechanical and neural mechanisms of balance control during walking are still poorly understood. In this study, we examined the body dynamic stability, activity of limb muscles, and activity of motor cortex neurons [primarily pyramidal tract neurons (PTNs)] in the cat during unconstrained walking and walking with a wide base of support (wide-stance walking). By recording three-dimensional full-body kinematics we found for the first time that during unconstrained walking the cat is dynamically unstable in the forward direction during stride phases when only two diagonal limbs support the body. In contrast to standing, an increased lateral between-paw distance during walking dramatically decreased the cat's body dynamic stability in double-support phases and prompted the cat to spend more time in three-legged support phases. Muscles contributing to abduction-adduction actions had higher activity during stance, while flexor muscles had higher activity during swing of wide-stance walking. The overwhelming majority of neurons in layer V of the motor cortex, 82% and 83% in the forelimb and hindlimb representation areas, respectively, were active differently during wide-stance walking compared with unconstrained condition, most often by having a different depth of stride-related frequency modulation along with a different mean discharge rate and/or preferred activity phase. Upon transition from unconstrained to wide-stance walking, proximal limb-related neuronal groups subtly but statistically significantly shifted their activity toward the swing phase, the stride phase where most of body instability occurs during this task. The data suggest that the motor cortex participates in maintenance of body dynamic stability during locomotion. PMID:24790167

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

PubMed

Nagy, Bernadett; Szabó, István; Papp, Szilárd; Takács, Gábor; Szalay, Csaba; Karádi, Zoltán

2012-03-20

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control. Copyright © 2012 Elsevier B.V. All rights reserved.

Involvement of Infralimbic Prefrontal Cortex but not Lateral Habenula in Dopamine Attenuation After Chronic Mild Stress.

PubMed

Moreines, Jared L; Owrutsky, Zoe L; Grace, Anthony A

2017-03-01

Emerging evidence supports a role for dopamine in major depressive disorder (MDD). We recently reported fewer spontaneously active ventral tegmental area (VTA) dopamine neurons (ie, reduced dopamine neuron population activity) in the chronic mild stress (CMS) rodent model of MDD. In this study, we examined the role of two brain regions that have been implicated in MDD in humans, the infralimbic prefrontal cortex (ILPFC)-that is, rodent homolog of Brodmann area 25 (BA25), and the lateral habenula (LHb) in the CMS-induced attenuation of dopamine neuron activity. The impact of activating the ILPFC or LHb was evaluated using single-unit extracellular recordings of identified VTA dopamine neurons. The involvement of each region in dopamine neuron attenuation following 5-7 weeks of CMS was then evaluated by selective inactivation. Activation of either ILPFC or LHb in normal rats potently suppressed dopamine neuron population activity, but in unique patterns. ILPFC activation selectively inhibited dopamine neurons in medial VTA, which were most impacted by CMS. Conversely, LHb activation selectively inhibited dopamine neurons in lateral VTA, which were unaffected by CMS. Moreover, only ILPFC inactivation restored dopamine neuron population activity to normal levels following CMS; LHb inactivation had no restorative effect. These data suggest that, in the CMS model of MDD, the ILPFC is the primary driver of diminished dopamine neuron responses. These findings support a neural substrate for ILPFC/BA25 linking affective and motivational circuitry dysfunction in MDD.

Sensory convergence in the parieto-insular vestibular cortex

PubMed Central

Shinder, Michael E.

2014-01-01

Vestibular signals are pervasive throughout the central nervous system, including the cortex, where they likely play different roles than they do in the better studied brainstem. Little is known about the parieto-insular vestibular cortex (PIVC), an area of the cortex with prominent vestibular inputs. Neural activity was recorded in the PIVC of rhesus macaques during combinations of head, body, and visual target rotations. Activity of many PIVC neurons was correlated with the motion of the head in space (vestibular), the twist of the neck (proprioceptive), and the motion of a visual target, but was not associated with eye movement. PIVC neurons responded most commonly to more than one stimulus, and responses to combined movements could often be approximated by a combination of the individual sensitivities to head, neck, and target motion. The pattern of visual, vestibular, and somatic sensitivities on PIVC neurons displayed a continuous range, with some cells strongly responding to one or two of the stimulus modalities while other cells responded to any type of motion equivalently. The PIVC contains multisensory convergence of self-motion cues with external visual object motion information, such that neurons do not represent a specific transformation of any one sensory input. Instead, the PIVC neuron population may define the movement of head, body, and external visual objects in space and relative to one another. This comparison of self and external movement is consistent with insular cortex functions related to monitoring and explains many disparate findings of previous studies. PMID:24671533

Spatio-Temporal Patterning in Primary Motor Cortex at Movement Onset.

PubMed

Best, Matthew D; Suminski, Aaron J; Takahashi, Kazutaka; Brown, Kevin A; Hatsopoulos, Nicholas G

2017-02-01

Voluntary movement initiation involves the engagement of large populations of motor cortical neurons around movement onset. Despite knowledge of the temporal dynamics that lead to movement, the spatial structure of these dynamics across the cortical surface remains unknown. In data from 4 rhesus macaques, we show that the timing of attenuation of beta frequency local field potential oscillations, a correlate of locally activated cortex, forms a spatial gradient across primary motor cortex (MI). We show that these spatio-temporal dynamics are recapitulated in the engagement order of ensembles of MI neurons. We demonstrate that these patterns are unique to movement onset and suggest that movement initiation requires a precise spatio-temporal sequential activation of neurons in MI. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex

PubMed Central

Bravo-Rivera, Christian; Rodriguez-Romaguera, Jose; Pagan-Rivera, Pablo A; Burgos-Robles, Anthony; Roman-Ortiz, Ciorana; Quirk, Gregory J

2018-01-01

Much is known about the neural circuits of conditioned fear and its relevance to understanding anxiety disorders, but less is known about other anxiety-related behaviors such as active avoidance. Using a tone-signaled, platform-mediated avoidance task, we observed that pharmacological inactivation of the prelimbic prefrontal cortex (PL) delayed avoidance. Surprisingly, optogenetic silencing of PL glutamatergic neurons did not delay avoidance. Consistent with this, inhibitory but not excitatory responses of rostral PL neurons were associated with avoidance training. To test the importance of these inhibitory responses, we optogenetically stimulated PL neurons to counteract the tone-elicited reduction in firing rate. Photoactivation of rostral (but not caudal) PL neurons at 4 Hz impaired avoidance. These findings suggest that inhibitory responses of rostral PL neurons signal the avoidability of a potential threat and underscore the importance of designing behavioral optogenetic studies based on neuronal firing responses. PMID:29851381

Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty

PubMed Central

Muller, Robert U.; Brown, Malcolm W.

2016-01-01

ABSTRACT There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:26972751

Choice-specific sequences in parietal cortex during a virtual-navigation decision task

PubMed Central

Harvey, Christopher D.; Coen, Philip; Tank, David W.

2012-01-01

The posterior parietal cortex (PPC) plays an important role in many cognitive behaviors; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioral choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (< 100 micrometers). During working memory decision tasks the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits. PMID:22419153

[The effect of the iontophoretic administration of glutamate on the organization of interneuronal interactions in the rabbit motor cortex].

PubMed

Khokhlova, V N

1999-01-01

The multiunit activity of neurons in the motor cortex was recorded in 6 rabbits during glutamate (or physiological saline) iontophoretic application. Interaction between the neighboring neurons was evaluated by means of statistical cross-correlation analysis of spike trains. It was found that glutamate did not produce significant changes in cross-correlations.

Sensitivity to perception level differentiates two subnetworks within the mirror neuron system.

PubMed

Simon, Shiri; Mukamel, Roy

2017-05-01

Mirror neurons are a subset of brain cells that discharge during action execution and passive observation of similar actions. An open question concerns the functional role of their ability to match observed and executed actions. Since understanding of goals requires conscious perception of actions, we expect that mirror neurons potentially involved in action goal coding, will be modulated by changes in action perception level. Here, we manipulated perception level of action videos depicting short hand movements and measured the corresponding fMRI BOLD responses in mirror regions. Our results show that activity levels within a network of regions, including the sensorimotor cortex, primary motor cortex, dorsal premotor cortex and posterior superior temporal sulcus, are sensitive to changes in action perception level, whereas activity levels in the inferior frontal gyrus, ventral premotor cortex, supplementary motor area and superior parietal lobule are invariant to such changes. In addition, this parcellation to two sub-networks manifest as smaller functional distances within each group of regions during task and resting state. Our results point to functional differences between regions within the mirror neurons system which may have implications with respect to their possible role in action understanding. © The Author (2017). Published by Oxford University Press.

Neurons in the Frontal Lobe Encode the Value of Multiple Decision Variables

PubMed Central

Kennerley, Steven W.; Dahmubed, Aspandiar F.; Lara, Antonio H.; Wallis, Jonathan D.

2009-01-01

A central question in behavioral science is how we select among choice alternatives to obtain consistently the most beneficial outcomes. Three variables are particularly important when making a decision: the potential payoff, the probability of success, and the cost in terms of time and effort. A key brain region in decision making is the frontal cortex as damage here impairs the ability to make optimal choices across a range of decision types. We simultaneously recorded the activity of multiple single neurons in the frontal cortex while subjects made choices involving the three aforementioned decision variables. This enabled us to contrast the relative contribution of the anterior cingulate cortex (ACC), the orbito-frontal cortex, and the lateral prefrontal cortex to the decision-making process. Neurons in all three areas encoded value relating to choices involving probability, payoff, or cost manipulations. However, the most significant signals were in the ACC, where neurons encoded multiplexed representations of the three different decision variables. This supports the notion that the ACC is an important component of the neural circuitry underlying optimal decision making. PMID:18752411

Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

PubMed Central

Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

2015-01-01

This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

Distinct Neural Activities in Premotor Cortex during Natural Vocal Behaviors in a New World Primate, the Common Marmoset (Callithrix jacchus).

PubMed

Roy, Sabyasachi; Zhao, Lingyun; Wang, Xiaoqin

2016-11-30

Although evidence from human studies has long indicated the crucial role of the frontal cortex in speech production, it has remained uncertain whether the frontal cortex in nonhuman primates plays a similar role in vocal communication. Previous studies of prefrontal and premotor cortices of macaque monkeys have found neural signals associated with cue- and reward-conditioned vocal production, but not with self-initiated or spontaneous vocalizations (Coudé et al., 2011; Hage and Nieder, 2013), which casts doubt on the role of the frontal cortex of the Old World monkeys in vocal communication. A recent study of marmoset frontal cortex observed modulated neural activities associated with self-initiated vocal production (Miller et al., 2015), but it did not delineate whether these neural activities were specifically attributed to vocal production or if they may result from other nonvocal motor activity such as orofacial motor movement. In the present study, we attempted to resolve these issues and examined single neuron activities in premotor cortex during natural vocal exchanges in the common marmoset (Callithrix jacchus), a highly vocal New World primate. Neural activation and suppression were observed both before and during self-initiated vocal production. Furthermore, by comparing neural activities between self-initiated vocal production and nonvocal orofacial motor movement, we identified a subpopulation of neurons in marmoset premotor cortex that was activated or suppressed by vocal production, but not by orofacial movement. These findings provide clear evidence of the premotor cortex's involvement in self-initiated vocal production in natural vocal behaviors of a New World primate. Human frontal cortex plays a crucial role in speech production. However, it has remained unclear whether the frontal cortex of nonhuman primates is involved in the production of self-initiated vocalizations during natural vocal communication. Using a wireless multichannel neural recording technique, we observed in the premotor cortex neural activation and suppression both before and during self-initiated vocalizations when marmosets, a highly vocal New World primate species, engaged in vocal exchanges with conspecifics. A novel finding of the present study is the discovery of a subpopulation of premotor cortex neurons that was activated by vocal production, but not by orofacial movement. These observations provide clear evidence of the premotor cortex's involvement in vocal production in a New World primate species. Copyright © 2016 the authors 0270-6474/16/3612168-12$15.00/0.

Neuronal encoding of subjective value in dorsal and ventral anterior cingulate cortex

PubMed Central

Cai, Xinying; Padoa-Schioppa, Camillo

2012-01-01

We examined the activity of individual cells in the primate anterior cingulate cortex during an economic choice task. In the experiments, monkeys chose between different juices offered in variables amounts and subjective values were inferred from the animals’ choices. We analyzed neuronal firing rates in relation to a large number of behaviorally relevant variables. We report three main results. First, there were robust differences between the dorsal bank (ACCd) and the ventral bank (ACCv) of the cingulate sulcus. Specifically, neurons in ACCd but not in ACCv were modulated by the movement direction. Furthermore, neurons in ACCd were most active prior to movement initiation whereas neurons in ACCv were most active after juice delivery. Second, neurons in both areas encoded the identity and the subjective value of the juice chosen by the animal. In contrast, neither region encoded the value of individual offers. Third, the population of value-encoding neurons in both ACCd and ACCv underwent range adaptation. With respect to economic choice, it is interesting to compare these areas with the orbitofrontal cortex (OFC), previously examined. While neurons in OFC encoded both pre-decision and post-decision variables, neurons in ACCd and ACCv only encoded post-decision variables. Moreover, the encoding of chosen value in ACCd and ACCv trailed that found in OFC. These observations indicate that economic decisions (value comparisons) take place upstream of ACCd and ACCv. The coexistence of choice outcome and movement signals in ACCd suggests that this area constitutes a getaway through which the choice system informs motor systems. PMID:22423100

From the motor cortex to the movement and back again.

PubMed

Teka, Wondimu W; Hamade, Khaldoun C; Barnett, William H; Kim, Taegyo; Markin, Sergey N; Rybak, Ilya A; Molkov, Yaroslav I

2017-01-01

The motor cortex controls motor behaviors by generating movement-specific signals and transmitting them through spinal cord circuits and motoneurons to the muscles. Precise and well-coordinated muscle activation patterns are necessary for accurate movement execution. Therefore, the activity of cortical neurons should correlate with movement parameters. To investigate the specifics of such correlations among activities of the motor cortex, spinal cord network and muscles, we developed a model for neural control of goal-directed reaching movements that simulates the entire pathway from the motor cortex through spinal cord circuits to the muscles controlling arm movements. In this model, the arm consists of two joints (shoulder and elbow), whose movements are actuated by six muscles (4 single-joint and 2 double-joint flexors and extensors). The muscles provide afferent feedback to the spinal cord circuits. Cortical neurons are defined as cortical "controllers" that solve an inverse problem based on a proposed straight-line trajectory to a target position and a predefined bell-shaped velocity profile. Thus, the controller generates a motor program that produces a task-specific activation of low-level spinal circuits that in turn induce the muscle activation realizing the intended reaching movement. Using the model, we describe the mechanisms of correlation between cortical and motoneuronal activities and movement direction and other movement parameters. We show that the directional modulation of neuronal activity in the motor cortex and the spinal cord may result from direction-specific dynamics of muscle lengths. Our model suggests that directional modulation first emerges at the level of muscle forces, augments at the motoneuron level, and further increases at the level of the motor cortex due to the dependence of frictional forces in the joints, contractility of the muscles and afferent feedback on muscle lengths and/or velocities.

Propofol and etomidate depress cortical, thalamic, and reticular formation neurons during anesthetic-induced unconsciousness.

PubMed

Andrada, Jason; Livingston, Preetha; Lee, Bong Jae; Antognini, Joseph

2012-03-01

The sites where anesthetics produce unconsciousness are not well understood. Likely sites include the cerebral cortex, thalamus, and reticular formation. We examined the effects of propofol and etomidate on neuronal function in the cortex, thalamus, and reticular formation in intact animals. Five cats had a recording well and electroencephalogram screws placed under anesthesia. After a 5-day recovery period, the cats were repeatedly studied 3 to 4 times per week. Neuronal (single-unit) activity in the cerebral cortex (areas 7, 18 and 19), thalamus (ventral posterolateral and ventral posteromedial nuclei and medial geniculate body), and reticular formation (mesencephalic reticular nucleus and central tegmental field) was recorded before, during, and after infusion of either propofol or etomidate. Cortical neuronal action potentials were analyzed separately as either regular spiking neurons or fast spiking neurons. Propofol and etomidate decreased the spontaneous firing rate of cortical neurons by 37% to 41%; fast spiking neurons and regular spiking neurons were similarly affected by the anesthetics. The neuronal firing rate in the thalamus and reticular formation decreased 30% to 49% by propofol and etomidate. The electroencephalogram shifted from a low-amplitude, high-frequency pattern to a high-amplitude, low-frequency pattern during drug infusion suggesting an anesthetic effect; peak power occurred at 12 to 13 Hz during propofol infusion. There were 2 major peaks during etomidate anesthesia: one at 12 to 14 Hz and another at 7 to 8 Hz. The cats were heavily sedated, with depressed corneal and whisker reflexes; withdrawal to noxious stimulation remained intact. These data show that neurons in the cortex, thalamus, and reticular formation are similarly depressed by propofol and etomidate. Although anesthetic depression of neuronal activity likely contributes to anesthetic-induced unconsciousness, further work is needed to determine how anesthetic effects at these sites interact to produce unconsciousness.

Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way.

PubMed

Espuny-Camacho, Ira; Michelsen, Kimmo A; Linaro, Daniele; Bilheu, Angéline; Acosta-Verdugo, Sandra; Herpoel, Adèle; Giugliano, Michele; Gaillard, Afsaneh; Vanderhaeghen, Pierre

2018-05-29

The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

PubMed

Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

2016-03-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

Endogenous Sequential Cortical Activity Evoked by Visual Stimuli

PubMed Central

Miller, Jae-eun Kang; Hamm, Jordan P.; Jackson, Jesse; Yuste, Rafael

2015-01-01

Although the functional properties of individual neurons in primary visual cortex have been studied intensely, little is known about how neuronal groups could encode changing visual stimuli using temporal activity patterns. To explore this, we used in vivo two-photon calcium imaging to record the activity of neuronal populations in primary visual cortex of awake mice in the presence and absence of visual stimulation. Multidimensional analysis of the network activity allowed us to identify neuronal ensembles defined as groups of cells firing in synchrony. These synchronous groups of neurons were themselves activated in sequential temporal patterns, which repeated at much higher proportions than chance and were triggered by specific visual stimuli such as natural visual scenes. Interestingly, sequential patterns were also present in recordings of spontaneous activity without any sensory stimulation and were accompanied by precise firing sequences at the single-cell level. Moreover, intrinsic dynamics could be used to predict the occurrence of future neuronal ensembles. Our data demonstrate that visual stimuli recruit similar sequential patterns to the ones observed spontaneously, consistent with the hypothesis that already existing Hebbian cell assemblies firing in predefined temporal sequences could be the microcircuit substrate that encodes visual percepts changing in time. PMID:26063915

Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum

PubMed Central

Sommer, Marc A.

2013-01-01

The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce “delay activity” between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move. PMID:23365182

Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

PubMed

Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

2017-09-01

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN. Copyright © 2017 the American Physiological Society.

Vibrissa motor cortex activity suppresses contralateral whisking behavior.

PubMed

Ebbesen, Christian Laut; Doron, Guy; Lenschow, Constanze; Brecht, Michael

2017-01-01

Anatomical, stimulation and lesion data implicate vibrissa motor cortex in whisker motor control. Work on motor cortex has focused on movement generation, but correlations between vibrissa motor cortex activity and whisking are weak. The exact role of vibrissa motor cortex remains unknown. We recorded vibrissa motor cortex neurons during various forms of vibrissal touch, which were invariably associated with whisker protraction and movement. Free whisking, object palpation and social touch all resulted in decreased cortical activity. To understand this activity decrease, we performed juxtacellular recordings, nanostimulation and in vivo whole-cell recordings. Social touch resulted in decreased spiking activity, decreased cell excitability and membrane hyperpolarization. Activation of vibrissa motor cortex by intracortical microstimulation elicited whisker retraction, as if to abort vibrissal touch. Various vibrissa motor cortex inactivation protocols resulted in contralateral protraction and increased whisker movements. These data collectively point to movement suppression as a prime function of vibrissa motor cortex activity.

Topography of sound level representation in the FM sweep selective region of the pallid bat auditory cortex.

PubMed

Measor, Kevin; Yarrow, Stuart; Razak, Khaleel A

2018-05-26

Sound level processing is a fundamental function of the auditory system. To determine how the cortex represents sound level, it is important to quantify how changes in level alter the spatiotemporal structure of cortical ensemble activity. This is particularly true for echolocating bats that have control over, and often rapidly adjust, call level to actively change echo level. To understand how cortical activity may change with sound level, here we mapped response rate and latency changes with sound level in the auditory cortex of the pallid bat. The pallid bat uses a 60-30 kHz downward frequency modulated (FM) sweep for echolocation. Neurons tuned to frequencies between 30 and 70 kHz in the auditory cortex are selective for the properties of FM sweeps used in echolocation forming the FM sweep selective region (FMSR). The FMSR is strongly selective for sound level between 30 and 50 dB SPL. Here we mapped the topography of level selectivity in the FMSR using downward FM sweeps and show that neurons with more monotonic rate level functions are located in caudomedial regions of the FMSR overlapping with high frequency (50-60 kHz) neurons. Non-monotonic neurons dominate the FMSR, and are distributed across the entire region, but there is no evidence for amplitopy. We also examined how first spike latency of FMSR neurons change with sound level. The majority of FMSR neurons exhibit paradoxical latency shift wherein the latency increases with sound level. Moreover, neurons with paradoxical latency shifts are more strongly level selective and are tuned to lower sound level than neurons in which latencies decrease with level. These data indicate a clustered arrangement of neurons according to monotonicity, with no strong evidence for finer scale topography, in the FMSR. The latency analysis suggests mechanisms for strong level selectivity that is based on relative timing of excitatory and inhibitory inputs. Taken together, these data suggest how the spatiotemporal spread of cortical activity may represent sound level. Copyright © 2018. Published by Elsevier B.V.

Visual dot interaction with short-term memory.

PubMed

Etindele Sosso, Faustin Armel

2017-06-01

Many neurodegenerative diseases have a memory component. Brain structures related to memory are affected by environmental stimuli, and it is difficult to dissociate effects of all behavior of neurons. Here, visual cortex of mice was stimulated with gratings and dot, and an observation of neuronal activity before and after was made. Bandwidth, firing rate and orientation selectivity index were evaluated. A primary communication between primary visual cortex and short-term memory appeared to show an interesting path to train cognitive circuitry and investigate the basics mechanisms of the neuronal learning. The findings also suggested the interplay between primary visual cortex and short-term plasticity. The properties inside a visual target shape the perception and affect the basic encoding. Using visual cortex, it may be possible to train the memory and improve the recovery of people with cognitive disabilities or memory deficit.

Temporal Coupling with Cortex Distinguishes Spontaneous Neuronal Activities in Identified Basal Ganglia-Recipient and Cerebellar-Recipient Zones of the Motor Thalamus

PubMed Central

Nakamura, Kouichi C.; Sharott, Andrew; Magill, Peter J.

2014-01-01

Neurons of the motor thalamus mediate basal ganglia and cerebellar influences on cortical activity. To elucidate the net result of γ-aminobutyric acid-releasing or glutamatergic bombardment of the motor thalamus by basal ganglia or cerebellar afferents, respectively, we recorded the spontaneous activities of thalamocortical neurons in distinct identified “input zones” in anesthetized rats during defined cortical activity states. Unexpectedly, the mean rates and brain state dependencies of the firing of neurons in basal ganglia-recipient zone (BZ) and cerebellar-recipient zone (CZ) were matched during slow-wave activity (SWA) and cortical activation. However, neurons were distinguished during SWA by their firing regularities, low-threshold spike bursts and, more strikingly, by the temporal coupling of their activities to ongoing cortical oscillations. The firing of neurons across the BZ was stronger and more precisely phase-locked to cortical slow (∼1 Hz) oscillations, although both neuron groups preferentially fired at the same phase. In contrast, neurons in BZ and CZ fired at different phases of cortical spindles (7–12 Hz), but with similar strengths of coupled firing. Thus, firing rates do not reflect the predicted inhibitory–excitatory imbalance across the motor thalamus, and input zone-specific temporal coding through oscillatory synchronization with the cortex could partly mediate the different roles of basal ganglia and cerebellum in behavior. PMID:23042738

Neuronal avalanches and coherence potentials

NASA Astrophysics Data System (ADS)

Plenz, D.

2012-05-01

The mammalian cortex consists of a vast network of weakly interacting excitable cells called neurons. Neurons must synchronize their activities in order to trigger activity in neighboring neurons. Moreover, interactions must be carefully regulated to remain weak (but not too weak) such that cascades of active neuronal groups avoid explosive growth yet allow for activity propagation over long-distances. Such a balance is robustly realized for neuronal avalanches, which are defined as cortical activity cascades that follow precise power laws. In experiments, scale-invariant neuronal avalanche dynamics have been observed during spontaneous cortical activity in isolated preparations in vitro as well as in the ongoing cortical activity of awake animals and in humans. Theory, models, and experiments suggest that neuronal avalanches are the signature of brain function near criticality at which the cortex optimally responds to inputs and maximizes its information capacity. Importantly, avalanche dynamics allow for the emergence of a subset of avalanches, the coherence potentials. They emerge when the synchronization of a local neuronal group exceeds a local threshold, at which the system spawns replicas of the local group activity at distant network sites. The functional importance of coherence potentials will be discussed in the context of propagating structures, such as gliders in balanced cellular automata. Gliders constitute local population dynamics that replicate in space after a finite number of generations and are thought to provide cellular automata with universal computation. Avalanches and coherence potentials are proposed to constitute a modern framework of cortical synchronization dynamics that underlies brain function.

Primary Auditory Cortex is Required for Anticipatory Motor Response.

PubMed

Li, Jingcheng; Liao, Xiang; Zhang, Jianxiong; Wang, Meng; Yang, Nian; Zhang, Jun; Lv, Guanghui; Li, Haohong; Lu, Jian; Ding, Ran; Li, Xingyi; Guang, Yu; Yang, Zhiqi; Qin, Han; Jin, Wenjun; Zhang, Kuan; He, Chao; Jia, Hongbo; Zeng, Shaoqun; Hu, Zhian; Nelken, Israel; Chen, Xiaowei

2017-06-01

The ability of the brain to predict future events based on the pattern of recent sensory experience is critical for guiding animal's behavior. Neocortical circuits for ongoing processing of sensory stimuli are extensively studied, but their contributions to the anticipation of upcoming sensory stimuli remain less understood. We, therefore, used in vivo cellular imaging and fiber photometry to record mouse primary auditory cortex to elucidate its role in processing anticipated stimulation. We found neuronal ensembles in layers 2/3, 4, and 5 which were activated in relationship to anticipated sound events following rhythmic stimulation. These neuronal activities correlated with the occurrence of anticipatory motor responses in an auditory learning task. Optogenetic manipulation experiments revealed an essential role of such neuronal activities in producing the anticipatory behavior. These results strongly suggest that the neural circuits of primary sensory cortex are critical for coding predictive information and transforming it into anticipatory motor behavior. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination

PubMed Central

Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K.; Fröhlich, Flavio

2016-01-01

Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition. PMID:27025995

Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination.

PubMed

Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K; Fröhlich, Flavio

2016-03-30

Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition.

Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus.

PubMed

Xiong, Xiaorui R; Liang, Feixue; Zingg, Brian; Ji, Xu-ying; Ibrahim, Leena A; Tao, Huizhong W; Zhang, Li I

2015-06-11

Defense against environmental threats is essential for animal survival. However, the neural circuits responsible for transforming unconditioned sensory stimuli and generating defensive behaviours remain largely unclear. Here, we show that corticofugal neurons in the auditory cortex (ACx) targeting the inferior colliculus (IC) mediate an innate, sound-induced flight behaviour. Optogenetic activation of these neurons, or their projection terminals in the IC, is sufficient for initiating flight responses, while the inhibition of these projections reduces sound-induced flight responses. Corticocollicular axons monosynaptically innervate neurons in the cortex of the IC (ICx), and optogenetic activation of the projections from the ICx to the dorsal periaqueductal gray is sufficient for provoking flight behaviours. Our results suggest that ACx can both amplify innate acoustic-motor responses and directly drive flight behaviours in the absence of sound input through corticocollicular projections to ICx. Such corticofugal control may be a general feature of innate defense circuits across sensory modalities.

Suppression of phase synchronisation in network based on cat's brain.

PubMed

Lameu, Ewandson L; Borges, Fernando S; Borges, Rafael R; Iarosz, Kelly C; Caldas, Iberê L; Batista, Antonio M; Viana, Ricardo L; Kurths, Jürgen

2016-04-01

We have studied the effects of perturbations on the cat's cerebral cortex. According to the literature, this cortex structure can be described by a clustered network. This way, we construct a clustered network with the same number of areas as in the cat matrix, where each area is described as a sub-network with a small-world property. We focus on the suppression of neuronal phase synchronisation considering different kinds of perturbations. Among the various controlling interventions, we choose three methods: delayed feedback control, external time-periodic driving, and activation of selected neurons. We simulate these interventions to provide a procedure to suppress undesired and pathological abnormal rhythms that can be associated with many forms of synchronisation. In our simulations, we have verified that the efficiency of synchronisation suppression by delayed feedback control is higher than external time-periodic driving and activation of selected neurons of the cat's cerebral cortex with the same coupling strengths.

Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating lysosomal acid sphingomyelinase.

PubMed

Zhu, Hong; Yoshimoto, Tanihiro; Yamashima, Tetsumori

2014-10-03

The inducible expression of heat shock protein 70.1 (Hsp70.1) plays cytoprotective roles in its molecular chaperone function. Binding of Hsp70 to an endolysosomal phospholipid, bis(monoacylglycero)phosphate (BMP), has been recently shown to stabilize lysosomal membranes by enhancing acid sphingomyelinase (ASM) activity in cancer cells. Using the monkey experimental paradigm, we have reported that calpain-mediated cleavage of oxidized Hsp70.1 causes neurodegeneration in the hippocampal cornu ammonis 1 (CA1), whereas expression of Hsp70.1 in the motor cortex without calpain activation contributes to neuroprotection. However, the molecular mechanisms of the lysosomal destabilization/stabilization determining neuronal cell fate have not been elucidated. To elucidate whether regulation of lysosomal ASM could affect the neuronal fate, we analyzed Hsp70.1-BMP binding and ASM activity by comparing the motor cortex and the CA1. We show that Hsp70.1 being localized at the lysosomal membrane, lysosomal lipid BMP levels, and the lipid binding domain of Hsp70.1 are crucial for Hsp70.1-BMP binding. In the postischemic motor cortex, Hsp70.1 being localized at the lysosomal membrane could bind to BMP without calpain activation and decreased BMP levels, resulting in increasing ASM activity and lysosomal stability. However, in the postischemic CA1, calpain activation and a concomitant decrease in the lysosomal membrane localization of Hsp70.1 and BMP levels may diminish Hsp70.1-BMP binding, resulting in decreased ASM activity and lysosomal rupture with leakage of cathepsin B into the cytosol. A TUNEL assay revealed the differential neuronal vulnerability between the CA1 and the motor cortex. These results suggest that regulation of ASM activation in vivo by Hsp70.1-BMP affects lysosomal stability and neuronal survival or death after ischemia/reperfusion. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Synaptic input correlations leading to membrane potential decorrelation of spontaneous activity in cortex.

PubMed

Graupner, Michael; Reyes, Alex D

2013-09-18

Correlations in the spiking activity of neurons have been found in many regions of the cortex under multiple experimental conditions and are postulated to have important consequences for neural population coding. While there is a large body of extracellular data reporting correlations of various strengths, the subthreshold events underlying the origin and magnitude of signal-independent correlations (called noise or spike count correlations) are unknown. Here we investigate, using intracellular recordings, how synaptic input correlations from shared presynaptic neurons translate into membrane potential and spike-output correlations. Using a pharmacologically activated thalamocortical slice preparation, we perform simultaneous recordings from pairs of layer IV neurons in the auditory cortex of mice and measure synaptic potentials/currents, membrane potentials, and spiking outputs. We calculate cross-correlations between excitatory and inhibitory inputs to investigate correlations emerging from the network. We furthermore evaluate membrane potential correlations near resting potential to study how excitation and inhibition combine and affect spike-output correlations. We demonstrate directly that excitation is correlated with inhibition thereby partially canceling each other and resulting in weak membrane potential and spiking correlations between neurons. Our data suggest that cortical networks are set up to partially cancel correlations emerging from the connections between neurons. This active decorrelation is achieved because excitation and inhibition closely track each other. Our results suggest that the numerous shared presynaptic inputs do not automatically lead to increased spiking correlations.

Figure-ground segregation at contours: a neural mechanism in the visual cortex of the alert monkey.

PubMed

Baumann, R; van der Zwan, R; Peterhans, E

1997-06-01

An important task of vision is the segregation of figure and ground in situations of spatial occlusion. Psychophysical evidence suggests that the depth order at contours is defined early in visual processing. We have analysed this process in the visual cortex of the alert monkey. The animals were trained on a visual fixation task which reinforced foveal viewing. During periods of active visual fixation, we recorded the responses of single neurons in striate and prestriate cortex (areas V1, V2, and V3/V3A). The stimuli mimicked situations of spatial occlusion, usually a uniform light (or dark) rectangle overlaying a grating texture of opposite contrast. The direction of figure and ground at the borders of these rectangles was defined by the direction of the terminating grating lines (occlusion cues). Neuronal responses were analysed with respect to figure-ground direction and contrast polarity at such contours. Striate neurons often failed to respond to such stimuli, or were selective for contrast polarity; others were non-selective. Some neurons preferred a certain combination of figure-ground direction and contrast polarity. These neurons were rare both in striate and prestriate cortex. The majority of neurons signalled figure-ground direction independent of contrast polarity. These neurons were only found in prestriate cortex. We explain these responses in terms of a model which also explains neuronal signals of illusory contours. These results suggest that occlusion cues are used at an early level of processing to segregate figure and ground at contours.

Neural correlates of working memory development in adolescent primates

PubMed Central

Zhou, Xin; Zhu, Dantong; Qi, Xue-Lian; Li, Sihai; King, Samson G.; Salinas, Emilio; Stanford, Terrence R.; Constantinidis, Christos

2016-01-01

Working memory ability matures after puberty, in parallel with structural changes in the prefrontal cortex, but little is known about how changes in prefrontal neuronal activity mediate this cognitive improvement in primates. To address this issue, we compare behavioural performance and neurophysiological activity in monkeys as they transitioned from puberty into adulthood. Here we report that monkeys perform working memory tasks reliably during puberty and show modest improvement in adulthood. The adult prefrontal cortex is characterized by increased activity during the delay period of the task but no change in the representation of stimuli. Activity evoked by distracting stimuli also decreases in the adult prefrontal cortex. The increase in delay period activity relative to the baseline activity of prefrontal neurons is the best correlate of maturation and is not merely a consequence of improved performance. Our results reveal neural correlates of the working memory improvement typical of primate adolescence. PMID:27827365

Optogenetic stimulation of cortex to map evoked whisker movements in awake head-restrained mice.

PubMed

Auffret, Matthieu; Ravano, Veronica L; Rossi, Giulia M C; Hankov, Nicolas; Petersen, Merissa F A; Petersen, Carl C H

2018-01-01

Whisker movements are used by rodents to touch objects in order to extract spatial and textural tactile information about their immediate surroundings. To understand the mechanisms of such active sensorimotor processing it is important to investigate whisker motor control. The activity of neurons in the neocortex affects whisker movements, but many aspects of the organization of cortical whisker motor control remain unknown. Here, we filmed whisker movements evoked by sequential optogenetic stimulation of different locations across the left dorsal sensorimotor cortex of awake head-restrained mice. Whisker movements were evoked by optogenetic stimulation of many regions in the dorsal sensorimotor cortex. Optogenetic stimulation of whisker sensory barrel cortex evoked retraction of the contralateral whisker after a short latency, and a delayed rhythmic protraction of the ipsilateral whisker. Optogenetic stimulation of frontal cortex evoked rhythmic bilateral whisker protraction with a longer latency compared to stimulation of sensory cortex. Compared to frontal cortex stimulation, larger amplitude bilateral rhythmic whisking in a less protracted position was evoked at a similar latency by stimulating a cortical region posterior to Bregma and close to the midline. These data suggest that whisker motor control might be broadly distributed across the dorsal mouse sensorimotor cortex. Future experiments must investigate the complex neuronal circuits connecting specific cell-types in various cortical regions with the whisker motor neurons located in the facial nucleus. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin.

PubMed

Ogino, Himari; Hisanaga, Arisa; Kohno, Takao; Kondo, Yuta; Okumura, Kyoko; Kamei, Takana; Sato, Tempei; Asahara, Hiroshi; Tsuiji, Hitomi; Fukata, Masaki; Hattori, Mitsuharu

2017-03-22

The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, noninvasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro , but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons. This enzyme was identified as a disintegrin and metalloproteinase with thrombospondin motifs-3 (ADAMTS-3). Recombinant ADAMTS-3 cleaved Reelin at the N-t site. ADAMTS-3 was expressed in excitatory neurons in the cerebral cortex and hippocampus. N-t cleavage of Reelin was markedly decreased in the embryonic cerebral cortex of ADAMTS-3 knock-out (KO) mice. Importantly, the amount of Dab1 and the phosphorylation level of Tau, which inversely correlate with Reelin activity, were significantly decreased in the cerebral cortex of ADAMTS-3 KO mice. Conditional KO mice, in which ADAMTS-3 was deficient only in the excitatory neurons of the forebrain, showed increased dendritic branching and elongation in the postnatal cerebral cortex. Our study shows that ADAMTS-3 is the major enzyme that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. Therefore, inhibition of ADAMTS-3 may be an effective treatment for neuropsychiatric and neurodegenerative disorders. SIGNIFICANCE STATEMENT ADAMTS-3 was identified as the protease that cleaves and inactivates Reelin in the cerebral cortex and hippocampus. ADAMTS-3 was expressed in the excitatory neurons of the embryonic and postnatal cerebral cortex and hippocampus. Cleavage by ADAMTS-3 is the major contributor of Reelin inactivation in vivo Tau phosphorylation was decreased and dendritic branching and elongation was increased in ADAMTS-3-deficient mice. Therefore, inhibition of ADAMTS-3 upregulates Reelin activity and may be a potential therapeutic strategy for the prevention or treatment of neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease. Copyright © 2017 the authors 0270-6474/17/373181-11$15.00/0.

Brain activation during fast driving in a driving simulator: the role of the lateral prefrontal cortex.

PubMed

Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

2008-07-16

Little is currently known about the neural underpinnings of the cognitive control of driving behavior in realistic situations and of the driver's speeding behavior in particular. In this study, participants drove in realistic scenarios presented in a high-end driving simulator. Scalp-recorded EEG oscillations in the alpha-band (8-13 Hz) with a 30-electrode montage were recorded while the participants drove under different conditions: (i) excessively fast (Fast), (ii) in a controlled manner at a safe speed (Correct), and (iii) impatiently in the context of testing traffic conditions (Impatient). Intracerebral sources of alpha-band activation were estimated using low resolution electrical tomography. Given that previous studies have shown a strong negative correlation between the Bold response in the frontal cortex and the alpha-band power, we used alpha-band-related activity as an estimation of frontal activation. Statistical analysis revealed more alpha-band-related activity (i.e. less neuronal activation) in the right lateral prefrontal cortex, including the dorsolateral prefrontal cortex, during fast driving. Those participants who speeded most and exhibited greater risk-taking behavior demonstrated stronger alpha-related activity (i.e. less neuronal activation) in the left anterior lateral prefrontal cortex. These findings are discussed in the context of current theories about the role of the lateral prefrontal cortex in controlling risk-taking behavior, task switching, and multitasking.

Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay Reach-to-Grasp Task

PubMed Central

Torre, Emiliano; Quaglio, Pietro; Denker, Michael; Brochier, Thomas; Riehle, Alexa

2016-01-01

The computational role of spike time synchronization at millisecond precision among neurons in the cerebral cortex is hotly debated. Studies performed on data of limited size provided experimental evidence that low-order correlations occur in relation to behavior. Advances in electrophysiological technology to record from hundreds of neurons simultaneously provide the opportunity to observe coordinated spiking activity of larger populations of cells. We recently published a method that combines data mining and statistical evaluation to search for significant patterns of synchronous spikes in massively parallel spike trains (Torre et al., 2013). The method solves the computational and multiple testing problems raised by the high dimensionality of the data. In the current study, we used our method on simultaneous recordings from two macaque monkeys engaged in an instructed-delay reach-to-grasp task to determine the emergence of spike synchronization in relation to behavior. We found a multitude of synchronous spike patterns aligned in both monkeys along a preferential mediolateral orientation in brain space. The occurrence of the patterns is highly specific to behavior, indicating that different behaviors are associated with the synchronization of different groups of neurons (“cell assemblies”). However, pooled patterns that overlap in neuronal composition exhibit no specificity, suggesting that exclusive cell assemblies become active during different behaviors, but can recruit partly identical neurons. These findings are consistent across multiple recording sessions analyzed across the two monkeys. SIGNIFICANCE STATEMENT Neurons in the brain communicate via electrical impulses called spikes. How spikes are coordinated to process information is still largely unknown. Synchronous spikes are effective in triggering a spike emission in receiving neurons and have been shown to occur in relation to behavior in a number of studies on simultaneous recordings of few neurons. We recently published a method to extend this type of investigation to larger data. Here, we apply it to simultaneous recordings of hundreds of neurons from the motor cortex of macaque monkeys performing a motor task. Our analysis reveals groups of neurons selectively synchronizing their activity in relation to behavior, which sheds new light on the role of synchrony in information processing in the cerebral cortex. PMID:27511007

Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay Reach-to-Grasp Task.

PubMed

Torre, Emiliano; Quaglio, Pietro; Denker, Michael; Brochier, Thomas; Riehle, Alexa; Grün, Sonja

2016-08-10

The computational role of spike time synchronization at millisecond precision among neurons in the cerebral cortex is hotly debated. Studies performed on data of limited size provided experimental evidence that low-order correlations occur in relation to behavior. Advances in electrophysiological technology to record from hundreds of neurons simultaneously provide the opportunity to observe coordinated spiking activity of larger populations of cells. We recently published a method that combines data mining and statistical evaluation to search for significant patterns of synchronous spikes in massively parallel spike trains (Torre et al., 2013). The method solves the computational and multiple testing problems raised by the high dimensionality of the data. In the current study, we used our method on simultaneous recordings from two macaque monkeys engaged in an instructed-delay reach-to-grasp task to determine the emergence of spike synchronization in relation to behavior. We found a multitude of synchronous spike patterns aligned in both monkeys along a preferential mediolateral orientation in brain space. The occurrence of the patterns is highly specific to behavior, indicating that different behaviors are associated with the synchronization of different groups of neurons ("cell assemblies"). However, pooled patterns that overlap in neuronal composition exhibit no specificity, suggesting that exclusive cell assemblies become active during different behaviors, but can recruit partly identical neurons. These findings are consistent across multiple recording sessions analyzed across the two monkeys. Neurons in the brain communicate via electrical impulses called spikes. How spikes are coordinated to process information is still largely unknown. Synchronous spikes are effective in triggering a spike emission in receiving neurons and have been shown to occur in relation to behavior in a number of studies on simultaneous recordings of few neurons. We recently published a method to extend this type of investigation to larger data. Here, we apply it to simultaneous recordings of hundreds of neurons from the motor cortex of macaque monkeys performing a motor task. Our analysis reveals groups of neurons selectively synchronizing their activity in relation to behavior, which sheds new light on the role of synchrony in information processing in the cerebral cortex. Copyright © 2016 Torre, et al.

A unified selection signal for attention and reward in primary visual cortex.

PubMed

Stănişor, Liviu; van der Togt, Chris; Pennartz, Cyriel M A; Roelfsema, Pieter R

2013-05-28

Stimuli associated with high rewards evoke stronger neuronal activity than stimuli associated with lower rewards in many brain regions. It is not well understood how these reward effects influence activity in sensory cortices that represent low-level stimulus features. Here, we investigated the effects of reward information in the primary visual cortex (area V1) of monkeys. We found that the reward value of a stimulus relative to the value of other stimuli is a good predictor of V1 activity. Relative value biases the competition between stimuli, just as has been shown for selective attention. The neuronal latency of this reward value effect in V1 was similar to the latency of attentional influences. Moreover, V1 neurons with a strong value effect also exhibited a strong attention effect, which implies that relative value and top-down attention engage overlapping, if not identical, neuronal selection mechanisms. Our findings demonstrate that the effects of reward value reach down to the earliest sensory processing levels of the cerebral cortex and imply that theories about the effects of reward coding and top-down attention on visual representations should be unified.

[Neuronal activity of monkey dorso-lateral premotor cortex during tasks of figure recognition guided motor sequence vs memorized spatial motor sequence].

PubMed

Chen, Y C; Huang, F D; Chen, N H; Shou, J Y; Wu, L

1998-04-01

In the last 2-3 decades the role of the premotor cortex (PM) of monkey in memorized spatial sequential (MSS) movements has been amply investigated. However, it is as yet not known whether PM participates in the movement sequence behaviour guided by recognition of visual figures (i.e. the figure-recognition sequence, FRS). In the present work three monkeys were trained to perform both FRS and MSS tasks. Postmortem examination showed that 202 cells were in the dorso-lateral premotor cortex. Among 111 cells recorded during the two tasks, more than 50% changed their activity during the cue periods in either task. During the response period, the ratios of cells with changes of firing rate in both FRS and MSS were high and roughly equal to each other, while during the image period, the proportion in the FRS (83.7%) was significantly higher than that in the MSS (66.7%). Comparison of neuronal activities during same motor sequence of two different tasks showed that during the image periods PM neuronal activities were more closely related to the FRS task, while during the cue periods no difference could be found. Analysis of cell responses showed that the neurons with longer latency were much more in MSS than in FRS in either cue or image period. The present results indicate that the premotor cortex participates in FRS motor sequence as well as in MSS and suggest that the dorso-lateral PM represents another subarea in function shared by both FRS and MSS tasks. However, in view of the differences of PM neuronal responses in cue or image periods of FRS and MSS tasks, it seems likely that neural networks involved in FRS and MSS tasks are different.

Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses

NASA Astrophysics Data System (ADS)

Parikh, Hirak; Marzullo, Timothy C.; Kipke, Daryl R.

2009-04-01

Improving cortical prostheses requires the development of recording neural interfaces that are efficient in terms of providing maximal control information with minimal interface complexity. While the typical approaches have targeted neurons in the motor cortex with multiple penetrating shanks, an alternative approach is to determine an efficient distribution of electrode sites within the layers of the cortex with fewer penetrating shanks. The objective of this study was to compare unit activity in the upper and lower layers of the cortex with respect to movement and direction in order to inform the design of penetrating microelectrodes. Four rats were implanted bilaterally with multi-site single-shank silicon microelectrode arrays in the neck/shoulder region of the motor cortex. We simultaneously recorded unit activity across all layers of the motor cortex while the animal was engaged in a movement direction task. Localization of the electrode array within the different layers of the cortex was determined by histology. We denoted units from layers 2 and 3 and units as upper layer units, and units from layers 5 and 6 as lower layer units. Analysis of unit spiking activity demonstrated that both the upper and lower layers encode movement and direction information. Unit responses in either cortical layer of the cortex were not preferentially associated with contralateral or ipsilateral movement. Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05). These results suggest that electrode sites clustered in the lower layers provide access to more salient control information for cortical neuroprostheses.

Molecular Regulation of DNA Damage-Induced Apoptosis in Neurons of Cerebral Cortex

PubMed Central

Liu, Zhiping; Pipino, Jacqueline; Chestnut, Barry; Landek, Melissa A.

2009-01-01

Cerebral cortical neuron degeneration occurs in brain disorders manifesting throughout life, but the mechanisms are understood poorly. We used cultured embryonic mouse cortical neurons and an in vivo mouse model to study mechanisms of DNA damaged-induced apoptosis in immature and differentiated neurons. p53 drives apoptosis of immature and differentiated cortical neurons through its rapid and prominent activation stimulated by DNA strand breaks induced by topoisomerase-I and -II inhibition. Blocking p53-DNA transactivation with α-pifithrin protects immature neurons; blocking p53-mitochondrial functions with μ-pifithrin protects differentiated neurons. Mitochondrial death proteins are upregulated in apoptotic immature and differentiated neurons and have nonredundant proapoptotic functions; Bak is more dominant than Bax in differentiated neurons. p53 phosphorylation is mediated by ataxia telangiectasia mutated (ATM) kinase. ATM inactivation is antiapoptotic, particularly in differentiated neurons, whereas inhibition of c-Abl protects immature neurons but not differentiated neurons. Cell death protein expression patterns in mouse forebrain are mostly similar to cultured neurons. DNA damage induces prominent p53 activation and apoptosis in cerebral cortex in vivo. Thus, DNA strand breaks in cortical neurons induce rapid p53-mediated apoptosis through actions of upstream ATM and c-Abl kinases and downstream mitochondrial death proteins. This molecular network operates through variations depending on neuron maturity. PMID:18820287

A Circuit for Motor Cortical Modulation of Auditory Cortical Activity

PubMed Central

Nelson, Anders; Schneider, David M.; Takatoh, Jun; Sakurai, Katsuyasu; Wang, Fan

2013-01-01

Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Using in vitro whole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Using in vivo intracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity. PMID:24005287

Basic mathematical rules are encoded by primate prefrontal cortex neurons

PubMed Central

Bongard, Sylvia; Nieder, Andreas

2010-01-01

Mathematics is based on highly abstract principles, or rules, of how to structure, process, and evaluate numerical information. If and how mathematical rules can be represented by single neurons, however, has remained elusive. We therefore recorded the activity of individual prefrontal cortex (PFC) neurons in rhesus monkeys required to switch flexibly between “greater than” and “less than” rules. The monkeys performed this task with different numerical quantities and generalized to set sizes that had not been presented previously, indicating that they had learned an abstract mathematical principle. The most prevalent activity recorded from randomly selected PFC neurons reflected the mathematical rules; purely sensory- and memory-related activity was almost absent. These data show that single PFC neurons have the capacity to represent flexible operations on most abstract numerical quantities. Our findings support PFC network models implementing specific “rule-coding” units that control the flow of information between segregated input, memory, and output layers. We speculate that these neuronal circuits in the monkey lateral PFC could readily have been adopted in the course of primate evolution for syntactic processing of numbers in formalized mathematical systems. PMID:20133872

Global Image Dissimilarity in Macaque Inferotemporal Cortex Predicts Human Visual Search Efficiency

PubMed Central

Sripati, Arun P.; Olson, Carl R.

2010-01-01

Finding a target in a visual scene can be easy or difficult depending on the nature of the distractors. Research in humans has suggested that search is more difficult the more similar the target and distractors are to each other. However, it has not yielded an objective definition of similarity. We hypothesized that visual search performance depends on similarity as determined by the degree to which two images elicit overlapping patterns of neuronal activity in visual cortex. To test this idea, we recorded from neurons in monkey inferotemporal cortex (IT) and assessed visual search performance in humans using pairs of images formed from the same local features in different global arrangements. The ability of IT neurons to discriminate between two images was strongly predictive of the ability of humans to discriminate between them during visual search, accounting overall for 90% of the variance in human performance. A simple physical measure of global similarity – the degree of overlap between the coarse footprints of a pair of images – largely explains both the neuronal and the behavioral results. To explain the relation between population activity and search behavior, we propose a model in which the efficiency of global oddball search depends on contrast-enhancing lateral interactions in high-order visual cortex. PMID:20107054

Developmental changes of neuronal networks associated with strategic social decision-making.

PubMed

Steinmann, Elisabeth; Schmalor, Antonia; Prehn-Kristensen, Alexander; Wolff, Stephan; Galka, Andreas; Möhring, Jan; Gerber, Wolf-Dieter; Petermann, Franz; Stephani, Ulrich; Siniatchkin, Michael

2014-04-01

One of the important prerequisites for successful social interaction is the willingness of each individual to cooperate socially. Using the ultimatum game, several studies have demonstrated that the process of decision-making to cooperate or to defeat in interaction with a partner is associated with activation of the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), anterior insula (AI), and inferior frontal cortex (IFC). This study investigates developmental changes in this neuronal network. 15 healthy children (8-12 years), 15 adolescents (13-18 years) and 15 young adults (19-28 years) were investigated using the ultimatum game. Neuronal networks representing decision-making based on strategic thinking were characterized using functional MRI. In all age groups, the process of decision-making in reaction to unfair offers was associated with hemodynamic changes in similar regions. Compared with children, however, healthy adults and adolescents revealed greater activation in the IFC and the fusiform gyrus, as well as the nucleus accumbens. In contrast, healthy children displayed more activation in the AI, the dorsal part of the ACC, and the DLPFC. There were no differences in brain activations between adults and adolescents. The neuronal mechanisms underlying strategic social decision making are already developed by the age of eight. Decision-making based on strategic thinking is associated with age-dependent involvement of different brain regions. Neuronal networks underlying theory of mind and reward anticipation are more activated in adults and adolescents with regard to the increasing perspective taking with age. In relation to emotional reactivity and respective compensatory coping in younger ages, children have higher activations in a neuronal network associated with emotional processing and executive control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Representation of the Numerosity ‘zero’ in the Parietal Cortex of the Monkey

PubMed Central

Okuyama, Sumito; Kuki, Toshinobu; Mushiake, Hajime

2015-01-01

Zero is a fundamental concept in mathematics and modern science. Empty sets are considered a precursor of the concept of numerosity zero and a part of numerical continuum. How is numerosity zero (the absence of visual items) represented in the primate cortex? To address this question, we trained monkeys to perform numerical operations including numerosity zero. Here we show a group of neurons in the posterior parietal cortex of the monkey activated in response to numerosity ‘zero’. ‘Zero’ neurons are classified into exclusive and continuous types; the exclusive type discretely encodes numerical absence and the continuous type encodes numerical absence as a part of a numerical continuum. “Numerosity-zero” neurons enhance behavioral discrimination of not only zero numerosity but also non-zero numerosities. Representation of numerosity zero in the parietal cortex may be a precursor of non-verbal concept of zero in primates. PMID:25989598

Representation of the Numerosity 'zero' in the Parietal Cortex of the Monkey.

PubMed

Okuyama, Sumito; Kuki, Toshinobu; Mushiake, Hajime

2015-05-22

Zero is a fundamental concept in mathematics and modern science. Empty sets are considered a precursor of the concept of numerosity zero and a part of numerical continuum. How is numerosity zero (the absence of visual items) represented in the primate cortex? To address this question, we trained monkeys to perform numerical operations including numerosity zero. Here we show a group of neurons in the posterior parietal cortex of the monkey activated in response to numerosity 'zero'. 'Zero' neurons are classified into exclusive and continuous types; the exclusive type discretely encodes numerical absence and the continuous type encodes numerical absence as a part of a numerical continuum. "Numerosity-zero" neurons enhance behavioral discrimination of not only zero numerosity but also non-zero numerosities. Representation of numerosity zero in the parietal cortex may be a precursor of non-verbal concept of zero in primates.

Heat shock protein defenses in the neo- and allocortex of the telencephalon

PubMed Central

Posimo, Jessica M.; Weilnau, Justin N.; Gleixner, Amanda M.; Broeren, Matthew T.; Weiland, Nicole L.; Brodsky, Jeffrey L.; Wipf, Peter; Leak, Rehana K.

2015-01-01

The telencephalic allocortex develops protein inclusions before the neocortex in many age-related proteinopathies. One major defense mechanism against proteinopathic stress is the heat shock protein (Hsp) network. We therefore contrasted Hsp defenses in stressed primary neo- and allocortical cells. Neocortical neurons were more resistant to the proteasome inhibitor MG132 than neurons from three allocortical subregions: entorhinal cortex, piriform cortex, and hippocampus. However, allocortical neurons exhibited higher MG132-induced increases in Hsp70 and Hsc70. MG132-treated allocortical neurons also exhibited greater levels of protein ubiquitination. Inhibition of Hsp70/Hsc70 activity synergistically exacerbated MG132 toxicity in allocortical neurons more than neocortical neurons, suggesting that the allocortex is more reliant on these Hsp defenses. In contrast, astrocytes harvested from neo- or allocortex did not differ in their response to Hsp70/Hsc70 inhibition. Consistent with the idea that chaperones are maximally engaged in allocortical neurons, an increase in Hsp70/Hsc70 activity was protective only in neocortical neurons. Finally, the levels of select Hsps were altered in neocortex and allocortex in vivo with aging. PMID:25771395

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

PubMed Central

Fan, Chunling; Zhang, Mengqi; Shang, Lei; Cynthia, Ngobe Akume; Li, Zhi; Yang, Zhenyu; Chen, Dan; Huang, Jufang; Xiong, Kun

2014-01-01

Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine (a marker of cell proliferation), c-Fos (a marker of cell viability) and NeuN (a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs. PMID:25206818

Manipulating neuronal activity with low frequency transcranial ultrasound

NASA Astrophysics Data System (ADS)

Moore, Michele Elizabeth

Stimulation of the rodent cerebral cortex is used to investigate the underlying biological basis for the restorative effects of slow wave sleep. Neuronal activation by optogenetic and ultrasound stimulation elicits changes in action potentials across the cerebral cortex that are recorded as electroencephalograms. Optogenetic stimulation requires an invasive implantation procedure limiting its application in human studies. We sought to determine whether ultrasound stimulation could be as effective as optogenetic techniques currently used, in an effort to further understand the physiological and metabolic requirements of sleep. We successfully recorded electroencephalograms in response to transcranial ultrasound stimulation of the barrel cortex at 1 and 7 Hz frequencies, comparing them to those recorded in response to optogenetic stimuli applied at the same frequencies. Our results showed application of a 473 nm blue LED positioned 6 cm above the skull and ultrasound stimulation at an output voltage of 1000 mVpp produced electroencephalograms with physiological responses of similar amplitude. We concluded that there exists an intensity-proportionate response in the optogenetic stimulation, but not with ultrasound stimulation at the frequencies we surveyed. Activation of neuronal cells in response to optogenetic stimulation in a Thy1-ChR2 transgenic mouse line is specifically targeted to pyramidal cells in the cerebral cortex. ChR2 responses to optogenetic stimulation are mediated by a focal activation of neuronal ion channels. We measured electrophysiological responses to ultrasound stimulation, comparing them to those recorded from optogenetic stimuli. Our results show striking similarities between ultrasound-induced responses and optogenetically-induced responses, which may indicate that transcranial ultrasound stimulation is also mediated by ion channel dependent processes in cerebral cortical neurons. The biophysical substrates for electrical excitability of neurons impose temporal constraints on their response to stimulation. If ultrasound-mediated responses are, in fact, ion channel mediated responses, ultrasound-induced responses should exhibit time-dependence characteristics similar to those of optogenetically-triggered responses. Minimal stimulus duration thresholds and the temporal limits of paired pulse facilitation for ultrasound stimulation were identical to those of optogenetic stimulation. Collectively, these experiments demonstrate an electrophysiological basis for low-frequency transcranial ultrasound stimulation of cerebral cortical neuronal activity.

Neurons in primary motor cortex engaged during action observation.

PubMed

Dushanova, Juliana; Donoghue, John

2010-01-01

Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These 'view' neurons were spatially intermingled with 'do' neurons, which are active only during movement performance. Simultaneously recorded 'view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. 'View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 'view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action.

[Activity of Retrosplenial Neurons during the First Days and after a Week Following the Learning of the Operant Food-Acquisition Task].

PubMed

Kuzina, E A; Gorkin, A G; Alexandrov, I

2015-01-01

Activity of single neurons in the retrosplenial cortex of rats during realization of the operant food-acquisition behavior was recorded. In the first group of rats the recordings were made in the first six days after learning of the task and in the second group--following a week of a rest after learning. There were no significant differences in proportion of neurons specialized in relation to the learned behavior; however in the first group 40% of these cells had specific activations only in 80-90%, but not in all (100%) realizations of their specific behavioral acts, while in the second group there were much less relative numbers (4%) of such cells. All neurons with not-100% activations on the early stages after the learning were specialized in relation to acts of approaching and pressing the pedal that rats acquired on the last session of learning. It could be supposed that during the first stages of consolidation of the operant skill some variable set of retrosplenial cortex neurons specialized to new behavioral acts can be involved.

Neurons in Primary Motor Cortex Encode Hand Orientation in a Reach-to-Grasp Task.

PubMed

Ma, Chaolin; Ma, Xuan; Fan, Jing; He, Jiping

2017-08-01

It is disputed whether those neurons in the primary motor cortex (M1) that encode hand orientation constitute an independent channel for orientation control in reach-to-grasp behaviors. Here, we trained two monkeys to reach forward and grasp objects positioned in the frontal plane at different orientation angles, and simultaneously recorded the activity of M1 neurons. Among the 2235 neurons recorded in M1, we found that 18.7% had a high correlation exclusively with hand orientation, 15.9% with movement direction, and 29.5% with both movement direction and hand orientation. The distributions of neurons encoding hand orientation and those encoding movement direction were not uniform but coexisted in the same region. The trajectory of hand rotation was reproduced by the firing patterns of the orientation-related neurons independent of the hand reaching direction. These results suggest that hand orientation is an independent component for the control of reaching and grasping activity.

Binge ethanol effects on prefrontal cortex neurons, spatial working memory and task-induced neuronal activation in male and female rats.

PubMed

West, Rebecca K; Maynard, Mark E; Leasure, J Leigh

2018-05-01

Excessive alcohol intake is associated with a multitude of health risks, especially for women. Recent studies in animal models indicate that the female brain is more negatively affected by alcohol, compared to the male brain. Among other regions, excessive alcohol consumption damages the frontal cortex, an area important for many functions and decision making of daily life. The objective of the present study was to determine whether the medial prefrontal cortex (mPFC) in female rats is selectively vulnerable to alcohol-induced damage. In humans, loss of prefrontal grey matter resulting from heavy alcohol consumption has been documented, however this volume loss is not necessarily due to a decrease in the number of neurons. We therefore quantified both number and nuclear volume of mPFC neurons following binge alcohol, as well as performance and neuronal activation during a prefrontal-dependent behavioral task. Adult male and female Long-Evans rats were assigned to binge or control groups and exposed to ethanol using a well-established 4-day model of alcohol-induced neurodegeneration. Both males and females had significantly smaller average neuronal nuclei volumes than their respective control groups immediately following alcohol binge, but neither sex showed a decrease in neuron number. Binged rats of both sexes initially showed spatial working memory deficits. Although they eventually achieved control performance, binged rats of both sexes showed increased c-Fos labeling in the mPFC during rewarded alternation, suggesting decreased neural efficiency. Overall, our results substantiate prior evidence indicating that the frontal cortex is vulnerable to alcohol, but also indicate that sex-specific vulnerability to alcohol may be brain region-dependent. Copyright © 2018 Elsevier Inc. All rights reserved.

Correlation Between Activation of the Prelimbic Cortex, Basolateral Amygdala, and Agranular Insular Cortex During Taste Memory Formation.

PubMed

Uematsu, Akira; Kitamura, Akihiko; Iwatsuki, Ken; Uneyama, Hisayuki; Tsurugizawa, Tomokazu

2015-09-01

Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown. Here, using awake functional magnetic resonance imaging and fiber tracking, we analyzed functional brain connectivity during the association of tastes and visceral illness. The blood oxygen level-dependent (BOLD) signal significantly increased in the PL after tastant and lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly correlated with those in the amygdala and agranular insular cortex (IC), which we found were also structurally connected to the PL by fiber tracking. To precisely examine these data, we then performed double immunofluorescence with a neuronal activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a fluorescent retrograde tracer in the PL. During CTA learning, we found an increase in the activity of excitatory neurons in the basolateral amygdala (BLA) or agranular IC that project to the PL. Taken together, these findings clearly identify a role of synchronized PL, agranular IC, and BLA activity in CTA learning. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Face processing in different brain areas, and critical band masking.

PubMed

Rolls, Edmund T

2008-09-01

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size, view, and spatial frequency of faces and objects, and that these neurons show rapid processing and rapid learning. Critical band spatial frequency masking is shown to be a property of these face-selective neurons and of the human visual perception of faces. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximizing the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalization, and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses generalize to other views of the same face. A theory is described of how such invariant representations may be produced by self-organizing learning in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory utilizes either temporal or spatial continuity with an associative synaptic modification rule. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye-gaze, face view, and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face-selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the human orbitofrontal and pregenual cingulate cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.

The representation of information about faces in the temporal and frontal lobes.

PubMed

Rolls, Edmund T

2007-01-07

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size and view of faces and objects, and that these neurons show rapid processing and rapid learning. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximising the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalisation and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses, generalise to other views of the same face. A theory is described of how such invariant representations may be produced in a hierarchically organised set of visual cortical areas with convergent connectivity. The theory proposes that neurons in these visual areas use a modified Hebb synaptic modification rule with a short-term memory trace to capture whatever can be captured at each stage that is invariant about objects as the objects change in retinal view, position, size and rotation. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye gaze, face view and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face-selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the orbitofrontal cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.

Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target Inhibitory and Excitatory Systems with Opposite Functions.

PubMed

Zikopoulos, Basilis; Höistad, Malin; John, Yohan; Barbas, Helen

2017-05-17

The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to the amygdala by density and size and proportion of large and efficient terminals. Moreover, whereas pOFC terminals in IM innervated each of the three distinct classes of inhibitory neurons, most targeted neurons expressing dopamine- and cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and inhibition of CeM, resulting in modulated autonomic function. By contrast, inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and triggers autonomic arousal. The findings provide a mechanism to help explain how a strong pOFC pathway, which is poised to moderate activity of CeM, through IM, can be undermined by the high level of dopamine during stress, resulting in collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic drive, as seen in chronic anxiety disorders. SIGNIFICANCE STATEMENT The dialogue between prefrontal cortex and amygdala allows thoughts and emotions to influence actions. The posterior orbitofrontal cortex sends a powerful pathway that targets a special class of amygdalar intercalated mass (IM) inhibitory neurons, whose wiring may help modulate autonomic function. By contrast, the anterior cingulate cortex innervates other amygdalar parts, activating circuits to help avoid danger. Most IM neurons in primates label for the protein DARPP-32, known to be activated or inhibited based on the level of dopamine. Stress markedly increases dopamine release and inhibits IM neurons, compromises prefrontal control of the amygdala, and sets off a general alarm system as seen in affective disorders, such as chronic anxiety and post-traumatic stress disorder. Copyright © 2017 the authors 0270-6474/17/375051-14$15.00/0.

Evaluating choices by single neurons in the frontal lobe: outcome value encoded across multiple decision variables

PubMed Central

Kennerley, Steven W.; Wallis, Jonathan D.

2009-01-01

Damage to the frontal lobe can cause severe decision-making impairments. A mechanism that may underlie this is that neurons in the frontal cortex encode many variables that contribute to the valuation of a choice, such as its costs, benefits and probability of success. However, optimal decision-making requires that one considers these variables, not only when faced with the choice, but also when evaluating the outcome of the choice, in order to adapt future behaviour appropriately. To examine the role of the frontal cortex in encoding the value of different choice outcomes, we simultaneously recorded the activity of multiple single neurons in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC) and lateral prefrontal cortex (LPFC) while subjects evaluated the outcome of choices involving manipulations of probability, payoff and cost. Frontal neurons encoded many of the parameters that enabled the calculation of the value of these variables, including the onset and offset of reward and the amount of work performed, and often encoded the value of outcomes across multiple decision variables. In addition, many neurons encoded both the predicted outcome during the choice phase of the task as well as the experienced outcome in the outcome phase of the task. These patterns of selectivity were more prevalent in ACC relative to OFC and LPFC. These results support a role for the frontal cortex, principally ACC, in selecting between choice alternatives and evaluating the outcome of that selection thereby ensuring that choices are optimal and adaptive. PMID:19453638

Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

PubMed

Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

2009-12-24

The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. 2009 Elsevier Inc. All rights reserved.

Anti-correlated cortical networks arise from spontaneous neuronal dynamics at slow timescales.

PubMed

Kodama, Nathan X; Feng, Tianyi; Ullett, James J; Chiel, Hillel J; Sivakumar, Siddharth S; Galán, Roberto F

2018-01-12

In the highly interconnected architectures of the cerebral cortex, recurrent intracortical loops disproportionately outnumber thalamo-cortical inputs. These networks are also capable of generating neuronal activity without feedforward sensory drive. It is unknown, however, what spatiotemporal patterns may be solely attributed to intrinsic connections of the local cortical network. Using high-density microelectrode arrays, here we show that in the isolated, primary somatosensory cortex of mice, neuronal firing fluctuates on timescales from milliseconds to tens of seconds. Slower firing fluctuations reveal two spatially distinct neuronal ensembles, which correspond to superficial and deeper layers. These ensembles are anti-correlated: when one fires more, the other fires less and vice versa. This interplay is clearest at timescales of several seconds and is therefore consistent with shifts between active sensing and anticipatory behavioral states in mice.

Cortical activity patterns predict speech discrimination ability

PubMed Central

Engineer, Crystal T; Perez, Claudia A; Chen, YeTing H; Carraway, Ryan S; Reed, Amanda C; Shetake, Jai A; Jakkamsetti, Vikram; Chang, Kevin Q; Kilgard, Michael P

2010-01-01

Neural activity in the cerebral cortex can explain many aspects of sensory perception. Extensive psychophysical and neurophysiological studies of visual motion and vibrotactile processing show that the firing rate of cortical neurons averaged across 50–500 ms is well correlated with discrimination ability. In this study, we tested the hypothesis that primary auditory cortex (A1) neurons use temporal precision on the order of 1–10 ms to represent speech sounds shifted into the rat hearing range. Neural discrimination was highly correlated with behavioral performance on 11 consonant-discrimination tasks when spike timing was preserved and was not correlated when spike timing was eliminated. This result suggests that spike timing contributes to the auditory cortex representation of consonant sounds. PMID:18425123

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

PubMed

Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Simultaneous selection by object-based attention in visual and frontal cortex

PubMed Central

Pooresmaeili, Arezoo; Poort, Jasper; Roelfsema, Pieter R.

2014-01-01

Models of visual attention hold that top-down signals from frontal cortex influence information processing in visual cortex. It is unknown whether situations exist in which visual cortex actively participates in attentional selection. To investigate this question, we simultaneously recorded neuronal activity in the frontal eye fields (FEF) and primary visual cortex (V1) during a curve-tracing task in which attention shifts are object-based. We found that accurate performance was associated with similar latencies of attentional selection in both areas and that the latency in both areas increased if the task was made more difficult. The amplitude of the attentional signals in V1 saturated early during a trial, whereas these selection signals kept increasing for a longer time in FEF, until the moment of an eye movement, as if FEF integrated attentional signals present in early visual cortex. In erroneous trials, we observed an interareal latency difference because FEF selected the wrong curve before V1 and imposed its erroneous decision onto visual cortex. The neuronal activity in visual and frontal cortices was correlated across trials, and this trial-to-trial coupling was strongest for the attended curve. These results imply that selective attention relies on reciprocal interactions within a large network of areas that includes V1 and FEF. PMID:24711379

Parvalbumin interneuron mediated feedforward inhibition controls signal output in the deep layers of the perirhinal‐entorhinal cortex

PubMed Central

Willems, Janske G. P.; Wadman, Wytse J.

2018-01-01

Abstract The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link between the neocortex and the hippocampus. However, neocortical activity is transmitted through the PER and LEC to the hippocampus with a low probability, suggesting the involvement of the inhibitory network. This study explored the role of interneuron mediated inhibition, activated by electrical stimulation in the agranular insular cortex (AiP), in the deep layers of the PER and LEC. Activated synaptic input by AiP stimulation rarely evoked action potentials in the PER‐LEC deep layer excitatory principal neurons, most probably because the evoked synaptic response consisted of a small excitatory and large inhibitory conductance. Furthermore, parvalbumin positive (PV) interneurons—a subset of interneurons projecting onto the axo‐somatic region of principal neurons—received synaptic input earlier than principal neurons, suggesting recruitment of feedforward inhibition. This synaptic input in PV interneurons evoked varying trains of action potentials, explaining the fast rising, long lasting synaptic inhibition received by deep layer principal neurons. Altogether, the excitatory input from the AiP onto deep layer principal neurons is overruled by strong feedforward inhibition. PV interneurons, with their fast, extensive stimulus‐evoked firing, are able to deliver this fast evoked inhibition in principal neurons. This indicates an essential role for PV interneurons in the gating mechanism of the PER‐LEC network. PMID:29341361

TBR2 antagonizes retinoic acid dependent neuronal differentiation by repressing Zfp423 during corticogenesis.

PubMed

Massimino, Luca; Flores-Garcia, Lisbeth; Di Stefano, Bruno; Colasante, Gaia; Icoresi-Mazzeo, Cecilia; Zaghi, Mattia; Hamilton, Bruce A; Sessa, Alessandro

2018-02-15

During cerebral cortex development, neural progenitors are required to elaborate a variety of cell differentiation signals to which they are continuously exposed. RA acid is a potent inducer of neuronal differentiation as it was found to influence cortical development. We report herein that TBR2, a transcription factor specific to Intermediate (Basal) Neural Progenitors (INPs), represses activation of the RA responsive element and expression of RA target genes in cell lines. This repressive action on RA signaling was functionally confirmed by the decrease of RA-mediated neuronal differentiation in neural stem cells stably overexpressing TBR2. In vivo mapping of RA activity in the developing cortex indicated that RA activity is detected in radial glial cells and subsequently downregulated in INPs, revealing a fine cell-type specific regulation of its signaling. Thus, TBR2 might be a molecular player in opposing RA signaling in INPs. Interestingly, this negative regulation is achieved at least in part by directly repressing the critical nuclear RA co-factor ZFP423. Indeed, we found ZFP423 to be expressed in the developing cortex and promote RA-dependent neuronal differentiation. These data indicate that TBR2 contributes to suppressing RA signaling in INPs, thereby enabling them to re-enter the cell cycle and delay neuronal differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

Persistent neuronal activity in human prefrontal cortex links perception and action

PubMed Central

Haller, Matar; Case, John; Crone, Nathan E.; Chang, Edward F.; King-Stephens, David; Laxer, Kenneth D.; Weber, Peter B.; Parvizi, Josef; Knight, Robert T.; Shestyuk, Avgusta Y.

2017-01-01

How do humans flexibly respond to changing environmental demands on a sub-second temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behavior, yet the core mechanisms that translate sensory information into behavior remain undefined. Utilizing direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity, indexed by the broadband gamma signal, while sixteen participants performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centered in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behavior.

Insular cortex activity and the evocation of laughter.

PubMed

Wattendorf, Elise; Westermann, Birgit; Lotze, Martin; Fiedler, Klaus; Celio, Marco R

2016-06-01

The insular cortex is fundamentally involved in the processing of interoceptive information. It has been postulated that the integrative monitoring of the bodily responses to environmental stimuli is crucial for the recognition and experience of emotions. Because emotional arousal is known to be closely coupled to functions of the anterior insula, we suspected laughter to be associated primarily with neuronal activity in this region. An anatomically constrained re-analysis of our imaging data pertaining to ticklish laughter, to inhibited ticklish laughter, and to voluntary laughter revealed regional differences in the levels of neuronal activity in the posterior and mid-/anterior portions of the insula. Ticklish laughter was associated specifically with right ventral anterior insular activity, which was not detected under the other two conditions. Hence, apparently, only laughter that is evoked as an emotional response bears the signature of autonomic arousal in the insular cortex. © 2015 Wiley Periodicals, Inc.

[The antioxidant prevention of disorders in calcium ion metabolism under the action of glutamate on the synaptosomes of the rat cerebral cortex].

PubMed

Avrova, N F; Shestak, K I; Zakharova, I O; Sokolova, T V; Tiurina, Iu Iu; Tiurin, V A

1999-04-01

An increase of intracellular calcium ion concentration and of the 45Ca2+ entry, a decrease in Na+,K(+)-ATPase activity, and activation of Na+/Ca2+ exchange were shown to be initiated by glutamate in the rat brain cortex synaptosomes. These effects could be prevented with antagonists and blocking agents of the NMDA receptors. Pre-incubation of the synaptosomes with alpha-tocopherol, superoxide dismutase, and ganglioside GM1 was shown to normalise [45Ca2+], the rate of 45Ca2+ entry, and the activity of Na+,K(+)-ATPase in the synaptosomes. The data obtained suggest that calcium ions entering the brain cortex neurones via the NMDA receptors in presence of excessive glutamate, trigger activation of free radical reactions damaging the neurones in ischemia, cerebral lesions, and other pathological conditions.

Control of Intermale Aggression by Medial Prefrontal Cortex Activation in the Mouse

PubMed Central

Takahashi, Aki; Nagayasu, Kazuki; Nishitani, Naoya; Kaneko, Shuji; Koide, Tsuyoshi

2014-01-01

Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits inter-male aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range. PMID:24740241

Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking.

PubMed

Augur, Isabel F; Wyckoff, Andrew R; Aston-Jones, Gary; Kalivas, Peter W; Peters, Jamie

2016-09-28

The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues. The ventromedial prefrontal cortex (vmPFC) projection to the nucleus accumbens shell is important for extinction of cocaine seeking, but its anatomical proximity to the relapse-promoting projection from the dorsomedial prefrontal cortex to the nucleus accumbens core makes it difficult to selectively enhance neuronal activity in one pathway or the other using traditional pharmacotherapy (e.g., systemically administered drugs). Viral-mediated gene delivery of an activating Gq-DREADD to vmPFC and/or vmPFC projections to the nucleus accumbens shell allows the chemogenetic exploitation of this extinction neural circuit to reduce cocaine seeking and was particularly effective against relapse triggered by cocaine reminder cues. Copyright © 2016 the authors 0270-6474/16/3610174-07$15.00/0.

Background sounds contribute to spectrotemporal plasticity in primary auditory cortex.

PubMed

Moucha, Raluca; Pandya, Pritesh K; Engineer, Navzer D; Rathbun, Daniel L; Kilgard, Michael P

2005-05-01

The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8-4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity.

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity

PubMed Central

Lo, Fu-Sun; Erzurumlu, Reha S.

2016-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated gene MET tyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAA receptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAA receptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. SIGNIFICANCE STATEMENT A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAA receptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. PMID:27030755

Distinct changes in evoked and resting globus pallidus activity in early and late Parkinson's disease experimental models.

PubMed

Zold, Camila L; Larramendy, Celia; Riquelme, Luis A; Murer, M Gustavo

2007-09-01

The main clinical manifestations of Parkinson's disease are caused by alterations of basal ganglia activity that are tied in with the progressive loss of mesencephalic dopaminergic neurons. Recent theoretical and modeling studies have suggested that changes in resting neuronal activity occurred later in the course of the disease than those evoked by phasic cortical input. However, there is no empirical support for this proposal. Here we report a marked increase in the responsiveness of globus pallidus neurons to electrical motor cortex stimulation, in the absence of noticeable changes in resting activity, in anesthetized rats that had consistently shown a deficit in forelimb use during behavioral testing before the experiments, and had approximately 45% dopamine neurons spared in the substantia nigra. Pallidal neurons were also over-responsive to motor cortex stimulation and lost spatial selectivity for cortical inputs in rats with extensive nigrostriatal damage. After partial lesions, over-responsiveness was mainly due to an increased proportion of neurons showing excitatory responses, while extensive lesions led to an increased likelihood of inhibitory responding neurons. Changes in resting neuronal activity, comprising pauses disrupting tonic discharge, occurred across different global brain states, including an activated condition which shares similarities with natural patterns of cortical activity seen in awake states and rapid eye-movement sleep, but only after massive nigrostriatal degeneration. These results suggest that a loss of functional segregation and an abnormal temporal encoding of phasic cortical inputs by globus pallidus neurons may contribute to inducing early motor impairment in Parkinson's disease.

Cell Class-Dependent Intracortical Connectivity and Output Dynamics of Layer 6 Projection Neurons of the Rat Primary Visual Cortex.

PubMed

Cotel, Florence; Fletcher, Lee N; Kalita-de Croft, Simon; Apergis-Schoute, John; Williams, Stephen R

2018-07-01

Neocortical information processing is powerfully influenced by the activity of layer 6 projection neurons through control of local intracortical and subcortical circuitry. Morphologically distinct classes of layer 6 projection neuron have been identified in the mammalian visual cortex, which exhibit contrasting receptive field properties, but little information is available on their functional specificity. To address this we combined anatomical tracing techniques with high-resolution patch-clamp recording to identify morphological and functional distinct classes of layer 6 projection neurons in the rat primary visual cortex, which innervated separable subcortical territories. Multisite whole-cell recordings in brain slices revealed that corticoclaustral and corticothalamic layer 6 projection neurons exhibited similar somatically recorded electrophysiological properties. These classes of layer 6 projection neurons were sparsely and reciprocally synaptically interconnected, but could be differentiated by cell-class, but not target-cell-dependent rules of use-dependent depression and facilitation of unitary excitatory synaptic output. Corticoclaustral and corticothalamic layer 6 projection neurons were differentially innervated by columnar excitatory circuitry, with corticoclaustral, but not corticothalamic, neurons powerfully driven by layer 4 pyramidal neurons, and long-range pathways conveyed in neocortical layer 1. Our results therefore reveal projection target-specific, functionally distinct, streams of layer 6 output in the rodent neocortex.

All-optical mapping of barrel cortex circuits based on simultaneous voltage-sensitive dye imaging and channelrhodopsin-mediated photostimulation

PubMed Central

Lo, Shun Qiang; Koh, Dawn X. P.; Sng, Judy C. G.; Augustine, George J.

2015-01-01

Abstract. We describe an experimental approach that uses light to both control and detect neuronal activity in mouse barrel cortex slices: blue light patterned by a digital micromirror array system allowed us to photostimulate specific layers and columns, while a red-shifted voltage-sensitive dye was used to map out large-scale circuit activity. We demonstrate that such all-optical mapping can interrogate various circuits in somatosensory cortex by sequentially activating different layers and columns. Further, mapping in slices from whisker-deprived mice demonstrated that chronic sensory deprivation did not significantly alter feedforward inhibition driven by layer 5 pyramidal neurons. Further development of voltage-sensitive optical probes should allow this all-optical mapping approach to become an important and high-throughput tool for mapping circuit interactions in the brain. PMID:26158003

Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

PubMed

Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

2017-11-17

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Persistent neural activity in auditory cortex is related to auditory working memory in humans and nonhuman primates

PubMed Central

Huang, Ying; Matysiak, Artur; Heil, Peter; König, Reinhard; Brosch, Michael

2016-01-01

Working memory is the cognitive capacity of short-term storage of information for goal-directed behaviors. Where and how this capacity is implemented in the brain are unresolved questions. We show that auditory cortex stores information by persistent changes of neural activity. We separated activity related to working memory from activity related to other mental processes by having humans and monkeys perform different tasks with varying working memory demands on the same sound sequences. Working memory was reflected in the spiking activity of individual neurons in auditory cortex and in the activity of neuronal populations, that is, in local field potentials and magnetic fields. Our results provide direct support for the idea that temporary storage of information recruits the same brain areas that also process the information. Because similar activity was observed in the two species, the cellular bases of some auditory working memory processes in humans can be studied in monkeys. DOI: http://dx.doi.org/10.7554/eLife.15441.001 PMID:27438411

Cortical presynaptic control of dorsal horn C-afferents in the rat.

PubMed

Moreno-López, Yunuen; Pérez-Sánchez, Jimena; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

2013-01-01

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C-fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C-fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C-fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C-fibers by means of GABAergic inhibitory interneurons.

Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

PubMed Central

Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

2013-01-01

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory interneurons. PMID:23935924

Synaptic Targets of Medial Septal Projections in the Hippocampus and Extrahippocampal Cortices of the Mouse

PubMed Central

Joshi, Abhilasha; Viney, Tim J.; Kis, Viktor

2015-01-01

Temporal coordination of neuronal assemblies among cortical areas is essential for behavioral performance. GABAergic projections from the medial septum and diagonal band complex exclusively innervate GABAergic interneurons in the rat hippocampus, contributing to the coordination of neuronal activity, including the generation of theta oscillations. Much less is known about the synaptic target neurons outside the hippocampus. To reveal the contribution of synaptic circuits involving the medial septum of mice, we have identified postsynaptic cortical neurons in wild-type and parvalbumin-Cre knock-in mice. Anterograde axonal tracing from the septum revealed extensive innervation of the hippocampus as well as the subiculum, presubiculum, parasubiculum, the medial and lateral entorhinal cortices, and the retrosplenial cortex. In all examined cortical regions, many septal GABAergic boutons were in close apposition to somata or dendrites immunopositive for interneuron cell-type molecular markers, such as parvalbumin, calbindin, calretinin, N-terminal EF-hand calcium-binding protein 1, cholecystokinin, reelin, or a combination of these molecules. Electron microscopic observations revealed septal boutons forming axosomatic or axodendritic type II synapses. In the CA1 region of hippocampus, septal GABAergic projections exclusively targeted interneurons. In the retrosplenial cortex, 93% of identified postsynaptic targets belonged to interneurons and the rest to pyramidal cells. These results suggest that the GABAergic innervation from the medial septum and diagonal band complex contributes to temporal coordination of neuronal activity via several types of cortical GABAergic interneurons in both hippocampal and extrahippocampal cortices. Oscillatory septal neuronal firing at delta, theta, and gamma frequencies may phase interneuron activity. SIGNIFICANCE STATEMENT Diverse types of GABAergic interneurons coordinate the firing of cortical principal cells required for memory processes. During wakefulness and rapid eye movement sleep, the rhythmic firing of cortical GABAergic neurons plays a key role in governing network activity. We investigated subcortical GABAergic projections in the mouse that extend from the medial septum/diagonal band nuclei to GABAergic neurons in the hippocampus and related extrahippocampal cortical areas, including the medial entorhinal cortex. These areas contribute to navigation and show theta rhythmic activity. We found selective GABAergic targeting of different groups of cortical GABAergic neurons, immunoreactive for combinations of cell-type markers. As septal GABAergic neurons also fire rhythmically, their selective innervation of cortical GABAergic neurons suggests an oscillatory synchronization of neuronal activity across functionally related areas. PMID:26631464

Relation between functional magnetic resonance imaging (fMRI) and single neuron, local field potential (LFP) and electrocorticography (ECoG) activity in human cortex.

PubMed

Ojemann, George A; Ojemann, Jeffrey; Ramsey, Nick F

2013-01-01

The relation between changes in the blood oxygen dependent metabolic changes imaged by functional magnetic resonance imaging (fMRI) and neural events directly recorded from human cortex from single neurons, local field potentials (LFPs) and electrocorticogram (ECoG) is critically reviewed, based on the published literature including findings from the authors' laboratories. All these data are from special populations, usually patients with medically refractory epilepsy, as this provides the major opportunity for direct cortical neuronal recording in humans. For LFP and ECoG changes are often sought in different frequency bands, for single neurons in frequency of action potentials. Most fMRI studies address issues of functional localization. The relation of those findings to localized changes in neuronal recordings in humans has been established in several ways. Only a few studies have directly compared changes in activity from the same sites in the same individual, using the same behavioral measure. More often the comparison has been between fMRI and electrophysiologic changes in populations recorded from the same functional anatomic system as defined by lesion effects; in a few studies those systems have been defined by fMRI changes such as the "default" network. The fMRI-electrophysiologic relationships have been evaluated empirically by colocalization of significant changes, and by quantitative analyses, often multiple linear regression. There is some evidence that the fMRI-electrophysiology relationships differ in different cortical areas, particularly primary motor and sensory cortices compared to association cortex, but also within areas of association cortex. Although crucial for interpretation of fMRI changes as reflecting neural activity in human cortex, controversy remains as to these relationships. Supported by: Dutch Technology Foundation and University of Utrecht Grant UGT7685, ERC-Advanced grant 320708 (NR) and NIH grant NS065186 (JO).

Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

PubMed Central

Kazu, Rodrigo S.; Maldonado, José; Mota, Bruno; Manger, Paul R.; Herculano-Houzel, Suzana

2014-01-01

Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are, however, distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires, and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex. PMID:25429261

Distributed coding of actual and hypothetical outcomes in the orbital and dorsolateral prefrontal cortex

PubMed Central

Abe, Hiroshi; Lee, Daeyeol

2011-01-01

SUMMARY Knowledge about hypothetical outcomes from unchosen actions is beneficial only when such outcomes can be correctly attributed to specific actions. Here, we show that during a simulated rock-paper-scissors game, rhesus monkeys can adjust their choice behaviors according to both actual and hypothetical outcomes from their chosen and unchosen actions, respectively. In addition, neurons in both dorsolateral prefrontal cortex and orbitofrontal cortex encoded the signals related to actual and hypothetical outcomes immediately after they were revealed to the animal. Moreover, compared to the neurons in the orbitofrontal cortex, those in the dorsolateral prefrontal cortex were more likely to change their activity according to the hypothetical outcomes from specific actions. Conjunctive and parallel coding of multiple actions and their outcomes in the prefrontal cortex might enhance the efficiency of reinforcement learning and also contribute to their context-dependent memory. PMID:21609828

Learning alters theta amplitude, theta-gamma coupling and neuronal synchronization in inferotemporal cortex.

PubMed

Kendrick, Keith M; Zhan, Yang; Fischer, Hanno; Nicol, Alister U; Zhang, Xuejuan; Feng, Jianfeng

2011-06-09

How oscillatory brain rhythms alone, or in combination, influence cortical information processing to support learning has yet to be fully established. Local field potential and multi-unit neuronal activity recordings were made from 64-electrode arrays in the inferotemporal cortex of conscious sheep during and after visual discrimination learning of face or object pairs. A neural network model has been developed to simulate and aid functional interpretation of learning-evoked changes. Following learning the amplitude of theta (4-8 Hz), but not gamma (30-70 Hz) oscillations was increased, as was the ratio of theta to gamma. Over 75% of electrodes showed significant coupling between theta phase and gamma amplitude (theta-nested gamma). The strength of this coupling was also increased following learning and this was not simply a consequence of increased theta amplitude. Actual discrimination performance was significantly correlated with theta and theta-gamma coupling changes. Neuronal activity was phase-locked with theta but learning had no effect on firing rates or the magnitude or latencies of visual evoked potentials during stimuli. The neural network model developed showed that a combination of fast and slow inhibitory interneurons could generate theta-nested gamma. By increasing N-methyl-D-aspartate receptor sensitivity in the model similar changes were produced as in inferotemporal cortex after learning. The model showed that these changes could potentiate the firing of downstream neurons by a temporal desynchronization of excitatory neuron output without increasing the firing frequencies of the latter. This desynchronization effect was confirmed in IT neuronal activity following learning and its magnitude was correlated with discrimination performance. Face discrimination learning produces significant increases in both theta amplitude and the strength of theta-gamma coupling in the inferotemporal cortex which are correlated with behavioral performance. A network model which can reproduce these changes suggests that a key function of such learning-evoked alterations in theta and theta-nested gamma activity may be increased temporal desynchronization in neuronal firing leading to optimal timing of inputs to downstream neural networks potentiating their responses. In this way learning can produce potentiation in neural networks simply through altering the temporal pattern of their inputs.

Learning alters theta amplitude, theta-gamma coupling and neuronal synchronization in inferotemporal cortex

PubMed Central

2011-01-01

Background How oscillatory brain rhythms alone, or in combination, influence cortical information processing to support learning has yet to be fully established. Local field potential and multi-unit neuronal activity recordings were made from 64-electrode arrays in the inferotemporal cortex of conscious sheep during and after visual discrimination learning of face or object pairs. A neural network model has been developed to simulate and aid functional interpretation of learning-evoked changes. Results Following learning the amplitude of theta (4-8 Hz), but not gamma (30-70 Hz) oscillations was increased, as was the ratio of theta to gamma. Over 75% of electrodes showed significant coupling between theta phase and gamma amplitude (theta-nested gamma). The strength of this coupling was also increased following learning and this was not simply a consequence of increased theta amplitude. Actual discrimination performance was significantly correlated with theta and theta-gamma coupling changes. Neuronal activity was phase-locked with theta but learning had no effect on firing rates or the magnitude or latencies of visual evoked potentials during stimuli. The neural network model developed showed that a combination of fast and slow inhibitory interneurons could generate theta-nested gamma. By increasing N-methyl-D-aspartate receptor sensitivity in the model similar changes were produced as in inferotemporal cortex after learning. The model showed that these changes could potentiate the firing of downstream neurons by a temporal desynchronization of excitatory neuron output without increasing the firing frequencies of the latter. This desynchronization effect was confirmed in IT neuronal activity following learning and its magnitude was correlated with discrimination performance. Conclusions Face discrimination learning produces significant increases in both theta amplitude and the strength of theta-gamma coupling in the inferotemporal cortex which are correlated with behavioral performance. A network model which can reproduce these changes suggests that a key function of such learning-evoked alterations in theta and theta-nested gamma activity may be increased temporal desynchronization in neuronal firing leading to optimal timing of inputs to downstream neural networks potentiating their responses. In this way learning can produce potentiation in neural networks simply through altering the temporal pattern of their inputs. PMID:21658251

Auditory cortex controls sound-driven innate defense behaviour through corticofugal projections to inferior colliculus

PubMed Central

Xiong, Xiaorui R.; Liang, Feixue; Zingg, Brian; Ji, Xu-ying; Ibrahim, Leena A.; Tao, Huizhong W.; Zhang, Li I.

2015-01-01

Defense against environmental threats is essential for animal survival. However, the neural circuits responsible for transforming unconditioned sensory stimuli and generating defensive behaviours remain largely unclear. Here, we show that corticofugal neurons in the auditory cortex (ACx) targeting the inferior colliculus (IC) mediate an innate, sound-induced flight behaviour. Optogenetic activation of these neurons, or their projection terminals in the IC, is sufficient for initiating flight responses, while the inhibition of these projections reduces sound-induced flight responses. Corticocollicular axons monosynaptically innervate neurons in the cortex of the IC (ICx), and optogenetic activation of the projections from the ICx to the dorsal periaqueductal gray is sufficient for provoking flight behaviours. Our results suggest that ACx can both amplify innate acoustic-motor responses and directly drive flight behaviours in the absence of sound input through corticocollicular projections to ICx. Such corticofugal control may be a general feature of innate defense circuits across sensory modalities. PMID:26068082

A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex

PubMed Central

Hakim, Richard; Shamardani, Kiarash

2018-01-01

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map. The network oscillations generated here emerge from non-periodic stimuli, and are stimulus size-dependent, coherent across cortical space, narrow band (30 Hz), and depend on SOM neuron but not parvalbumin (PV) neuron activity; similar to visually induced gamma oscillations observed in vivo. Gamma oscillations generated in separate cortical locations exhibited high coherence as far apart as 850 μm, and lateral gamma entrainment depended on SOM neuron activity. These data identify a circuit that is sufficient to mediate long-range gamma-band coherence in the primary visual cortex. PMID:29480803

Advanced Age Dissociates Dual Functions of the Perirhinal Cortex

PubMed Central

Burke, Sara N.; Maurer, Andrew P.; Nematollahi, Saman; Uprety, Ajay; Wallace, Jenelle L.

2014-01-01

The perirhinal cortex (PRC) is proposed to both represent high-order sensory information and maintain those representations across delays. These cognitive processes are required for recognition memory, which declines during normal aging. Whether or not advanced age affects the ability of PRC principal cells to support these dual roles, however, is not known. The current experiment recorded PRC neurons as young and aged rats traversed a track. When objects were placed on the track, a subset of the neurons became active at discrete locations adjacent to objects. Importantly, the aged rats had a lower proportion of neurons that were activated by objects. Once PRC activity patterns in the presence of objects were established, however, both age groups maintained these representations across delays up to 2 h. These data support the hypothesis that age-associated deficits in stimulus recognition arise from impairments in high-order stimulus representation rather than difficulty in sustaining stable activity patterns over time. PMID:24403147

Advanced age dissociates dual functions of the perirhinal cortex.

PubMed

Burke, Sara N; Maurer, Andrew P; Nematollahi, Saman; Uprety, Ajay; Wallace, Jenelle L; Barnes, Carol A

2014-01-08

The perirhinal cortex (PRC) is proposed to both represent high-order sensory information and maintain those representations across delays. These cognitive processes are required for recognition memory, which declines during normal aging. Whether or not advanced age affects the ability of PRC principal cells to support these dual roles, however, is not known. The current experiment recorded PRC neurons as young and aged rats traversed a track. When objects were placed on the track, a subset of the neurons became active at discrete locations adjacent to objects. Importantly, the aged rats had a lower proportion of neurons that were activated by objects. Once PRC activity patterns in the presence of objects were established, however, both age groups maintained these representations across delays up to 2 h. These data support the hypothesis that age-associated deficits in stimulus recognition arise from impairments in high-order stimulus representation rather than difficulty in sustaining stable activity patterns over time.

Mechanisms underlying a thalamocortical transformation during active tactile sensation

PubMed Central

Gutnisky, Diego Adrian; Yu, Jianing; Hires, Samuel Andrew; To, Minh-Son; Svoboda, Karel

2017-01-01

During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain’s ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit. PMID:28591219

Parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice

PubMed Central

Sreenivasan, Varun; Karmakar, Kajari; Rijli, Filippo M; Petersen, Carl C H

2015-01-01

Mice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. Whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. The signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. Here, we delineate two pathways, one originating from primary whisker somatosensory cortex (wS1) and the other from whisker motor cortex (wM1), that control qualitatively distinct movements of contralateral whiskers. Optogenetic stimulation of wS1 drove retraction of contralateral whiskers while stimulation of wM1 drove rhythmic whisker protraction. To map brainstem pathways connecting these cortical areas to whisker motor neurons, we used a combination of anterograde tracing using adenoassociated virus injected into neocortex and retrograde tracing using monosynaptic rabies virus injected into whisker muscles. Our data are consistent with wS1 driving whisker retraction by exciting glutamatergic premotor neurons in the rostral spinal trigeminal interpolaris nucleus, which in turn activate the motor neurons innervating the extrinsic retractor muscle nasolabialis. The rhythmic whisker protraction evoked by wM1 stimulation might be driven by excitation of excitatory and inhibitory premotor neurons in the brainstem reticular formation innervating both intrinsic and extrinsic muscles. Our data therefore begin to unravel the neuronal circuits linking the neocortex to whisker motor neurons. PMID:25476605

Drivers from the deep: the contribution of collicular input to thalamocortical processing.

PubMed

Wurtz, Robert H; Sommer, Marc A; Cavanaugh, James

2005-01-01

A traditional view of the thalamus is that it is a relay station which receives sensory input and conveys this information to cortex. This sensory input determines most of the properties of first order thalamic neurons, and so is said to drive, rather than modulate, these neurons. This holds as a rule for first order thalamic nuclei, but in contrast, higher order thalamic nuclei receive much of their driver input back from cerebral cortex. In addition, higher order thalamic neurons receive inputs from subcortical movement-related centers. In the terminology popularized from studies of the sensory system, can we consider these ascending motor inputs to thalamus from subcortical structures to be modulators, subtly influencing the activity of their target neurons, or drivers, dictating the activity of their target neurons? This chapter summarizes relevant evidence from neuronal recording, inactivation, and stimulation of pathways projecting from the superior colliculus through thalamus to cerebral cortex. The study concludes that many inputs to the higher order nuclei of the thalamus from subcortical oculomotor areas - from the superior colliculus and probably other midbrain and pontine regions - should be regarded as motor drivers analogous to the sensory drivers at the first order thalamic nuclei. These motor drivers at the thalamus are viewed as being at the top of a series of feedback loops that provide information on impending actions, just as sensory drivers provide information about the external environment.

Evolution of columns, modules, and domains in the neocortex of primates.

PubMed

Kaas, Jon H

2012-06-26

The specialized regions of neocortex of mammals, called areas, have been divided into smaller functional units called minicolumns, columns, modules, and domains. Here we describe some of these functional subdivisions of areas in primates and suggest when they emerged in mammalian evolution. We distinguish several types of these smaller subdivisions. Minicolumns, vertical arrays of neurons that are more densely interconnected with each other than with laterally neighboring neurons, are present in all cortical areas. Classic columns are defined by a repeating pattern of two or more types of cortex distinguished by having different inputs and neurons with different response properties. Sensory stimuli that continuously vary along a stimulus dimension may activate groups of neurons that vary continuously in location, producing "columns" without specific boundaries. Other groups or columns of cortical neurons are separated by narrow septa of fibers that reflect discontinuities in the receptor sheet. Larger regions of posterior parietal cortex and frontal motor cortex are parts of networks devoted to producing different sequences of movements. We distinguish these larger functionally distinct regions as domains. Columns of several types have evolved independently a number of times. Some of the columns found in primates likely emerged with the first primates, whereas others likely were present in earlier ancestors. The sizes and shapes of columns seem to depend on the balance of neuron activation patterns and molecular signals during development.

Mirror neuron function, psychosis, and empathy in schizophrenia

PubMed Central

McCormick, Laurie M.; Brumm, Michael C.; Beadle, Janelle N.; Paradiso, Sergio; Yamada, Thoru; Andreasen, Nancy

2013-01-01

Processing of social and emotional information has been shown to be disturbed in schizophrenia. The biological underpinnings of these abnormalities may be explained by an abnormally functioning mirror neuron system. Yet the relationship between mirror neuron system activity in schizophrenia, as measured using an electroencephalography (EEG) paradigm, and socio-emotional functioning has not been assessed. The present research measured empathy and mirror neuron activity using an established EEG paradigm assessing the integrity of the Mu rhythm (8–13 Hz) suppression over the sensorimotor cortex during observed and actual hand movement in 16 schizophrenia-spectrum disorder (SSD) participants (n=8 actively psychotic and n=8 in residual illness phase) and 16 age- and gender-matched healthy comparison participants. Actively psychotic SSD participants showed significantly greater mu suppression over the sensorimotor cortex of the left hemisphere than residual phase SSD and healthy comparison individuals. The latter two groups showed similar levels of mu suppression. Greater left-sided mu suppression was positively correlated with psychotic symptoms (i.e., greater mu suppression/mirror neuron activity was highest among subjects with the greater severity of psychotic symptoms). SSD subjects tended to have significantly higher levels of Personal Distress (as measured by the Interpersonal Reactivity Index) than healthy participants. The present study suggests that abnormal mirror neuron activity may exist among patients with schizophrenia during the active (psychotic) phase of the illness, and correlates with severity of psychosis. PMID:22510432

Enhanced responses of the anterior cingulate cortex neurones to colonic distension in viscerally hypersensitive rats

PubMed Central

Gao, Jun; Wu, Xiaoyin; Owyang, Chung; Li, Ying

2006-01-01

The anterior cingulate cortex (ACC) is critically involved in processing the affective component of pain sensation. Visceral hypersensitivity is a characteristic of irritable bowel syndrome. Electrophysiological activity of the ACC with regard to visceral sensitization has not been characterized. Single ACC neuronal activities in response to colorectal distension (CRD) were recorded in control, sham-treated rats and viscerally hypersensitive (EA) rats (induced by chicken egg albumin injection, i.p). The ACC neurones of controls failed to respond to 10 or 30 mmHg CRD; only 22% were activated by 50 mmHg CRD. Among the latter, 16.4% exhibited an excitatory response to CRD and were labelled ‘CRD-excited’ neurones. In contrast, CRD (10, 30 and 50 mmHg) markedly increased ACC neuronal responses of EA rats (10%, 28% and 47%, respectively). CRD produced greater pressure-dependent increases in ACC spike firing rates in EA rats compared with controls. Splanchnicectomy combined with pelvic nerve section abolished ACC responses to CRD in EA rats. Spontaneous activity in CRD-excited ACC neurones was significantly higher in EA rats than in controls. CRD-excited ACC neurones in control and EA rats (7 of 16 (42%) and 8 of 20 (40%), respectively) were activated by transcutaneous electrical and thermal stimuli. However, ACC neuronal activity evoked by noxious cutaneous stimuli did not change significantly in EA rats. This study identifies CRD-responsive neurones in the ACC and establishes for the first time that persistence of a heightened visceral afferent nociceptive input to the ACC induces ACC sensitization, characterized by increased spontaneous activity of CRD-excited neurones, decreased CRD pressure threshold, and increased response magnitude. Enhanced ACC nociceptive transmission in viscerally hypersensitive rats is restricted to visceral afferent input. PMID:16239277

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

PubMed

Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

2017-03-01

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increasing glucose load while maintaining normoglycemia does not evoke neuronal damage in prolonged critically ill rabbits.

PubMed

Sonneville, Romain; den Hertog, Heleen M; Derde, Sarah; Güiza, Fabian; Derese, Inge; Van den Berghe, Greet; Vanhorebeek, Ilse

2013-12-01

Preventing severe hyperglycemia with insulin reduced the neuropathological alterations in frontal cortex during critical illness. We investigated the impact of increasing glucose load under normoglycemia on neurons and glial cells. Hyperinflammatory critically ill rabbits were randomized to fasting or combined parenteral nutrition containing progressively increasing amounts of glucose (low, intermediate, high) within the physiological range but with a similar amount of amino acids and lipids. In all groups, normoglycemia was maintained with insulin. On day 7, we studied the neuropathological alterations in frontal cortex neurons, astrocytes and microglia, and MnSOD as marker of oxidative stress. The percentage of damaged neurons was comparable among all critically ill and healthy rabbits. Critical illness induced an overall 1.8-fold increase in astrocyte density and activation status, largely irrespective of the nutritional intake. The percentage of microglia activation in critically ill rabbits was comparable with that in healthy rabbits, irrespective of glucose load. Likewise, MnSOD expression was comparable in critically ill and healthy rabbits without any clear impact of the nutritional interventions. During prolonged critical illness, increasing intravenous glucose infusion while strictly maintaining normoglycemia appeared safe for neuronal integrity and did not substantially affect glial cells in frontal cortex. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Mnemonic neuronal activity in somatosensory cortex.

PubMed Central

Zhou, Y D; Fuster, J M

1996-01-01

Single-unit activity was recorded from the hand areas of the somatosensory cortex of monkeys trained to perform a haptic delayed matching to sample task with objects of identical dimensions but different surface features. During the memory retention period of the task (delay), many units showed sustained firing frequency change, either excitation or inhibition. In some cases, firing during that period was significantly higher after one sample object than after another. These observations indicate the participation of somatosensory neurons not only in the perception but in the short-term memory of tactile stimuli. Neurons most directly implicated in tactile memory are (i) those with object-selective delay activity, (ii) those with nondifferential delay activity but without activity related to preparation for movement, and (iii) those with delay activity in the haptic-haptic delayed matching task but no such activity in a control visuo-haptic delayed matching task. The results indicate that cells in early stages of cortical somatosensory processing participate in haptic short-term memory. PMID:8927629

Determining which mechanisms lead to activation in the motor cortex: a modeling study of transcranial magnetic stimulation using realistic stimulus waveforms and sulcal geometry1

PubMed Central

Salvador, R.; Silva, S.; Basser, P. J.; Miranda, P. C.

2010-01-01

Objective To determine which mechanisms lead to activation of neurons in the motor cortex during transcranial magnetic stimulation (TMS) with different current directions and pulse waveforms. Methods The total electric field induced in a simplified model of a cortical sulcus by a figure-eight coil was calculated using the finite element method (FEM). This electric field was then used as the input to determine the response of compartmental models of several types of neurons. Results The modeled neurons were stimulated at different sites: fiber bends for pyramidal tract neurons, axonal terminations for cortical interneurons and axon collaterals, and a combination of both for pyramidal association fibers. All neurons were more easily stimulated by a PA directed electric field, except association fibers. Additionally, the second phase of a biphasic pulse was found to be more efficient than the first phase of either monophasic or biphasic pulses. Conclusion The stimulation threshold for different types of neurons depends on the pulse waveform and current direction. The reported results might account for the range of responses obtained in TMS of the motor cortex when using different stimulation parameters. Significance Modeling studies combining electric field calculations and neuronal models may lead to a deeper understanding of the effect of the TMS-induced electric field on cortical tissue, and may be used to evaluate improvements in TMS coil and waveform design. PMID:21035390

CREB regulates memory allocation in the insular cortex

PubMed Central

Sano, Yoshitake; Shobe, Justin L.; Zhou, Miou; Huang, Shan; Shuman, Tristan; Cai, Denise J.; Golshani, Peyman; Kamata, Masakazu; Silva, Alcino J.

2016-01-01

Summary The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory [1, 2]. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cAMP response element binding protein (CREB) are more likely to be recruited into encoding and storing fear memory [3–6]. To determine whether specific mechanisms also regulate memory allocation in other brain regions, and whether CREB also has a role in this process, we studied insular cortical memory representations for conditioned taste aversion (CTA). In this task, an animal learns to associate a taste (CS) with the experience of malaise (such as that induced by LiCl; US). The insular cortex is required for CTA memory formation and retrieval [7–12]. CTA learning activates a subpopulation of neurons in this structure [13–15], and the insular cortex and the basolateral amygdala (BLA) interact during CTA formation [16, 17]. Here, we used a combination of approaches, including viral vector transfections of insular cortex, arc Fluorescence In Situ Hybridization (FISH) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system, to show that CREB levels determine which insular cortical neurons go on to encode a given conditioned taste memory. PMID:25454591

Neuron discharges in the rat auditory cortex during electrical intracortical stimulation.

PubMed

Maldonado, P E; Altman, J A; Gerstein, G L

1998-01-01

Studies were carried out in rats anesthetized with ketamine or nembutal, with recording of multicellular activity (with separate identification of responses from individual neurons) in the primary auditory cortex before and after electrical intracortical microstimulation. These experiments showed that about half of the set of neurons studied produced responses to short tonal bursts, these responses having two components-initial discharges arising in response to the sound, and afterdischarge occurring after pauses of 50-100 msec. Afterdischarges lasted at least several seconds, and were generally characterized by a rhythmic structure (with a frequency of 8-12 Hz). After electrical microstimulation, the level of spike activity increased, especially in afterdischarges, and this increase could last up to 4 h. Combined peristimulus histograms, cross-correlations, and gravitational analyses were used to demonstrate interactions of neurons, which increased after electrical stimulation and were especially pronounced in the response afterdischarges.

Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture.

PubMed

Paşca, Anca M; Sloan, Steven A; Clarke, Laura E; Tian, Yuan; Makinson, Christopher D; Huber, Nina; Kim, Chul Hoon; Park, Jin-Young; O'Rourke, Nancy A; Nguyen, Khoa D; Smith, Stephen J; Huguenard, John R; Geschwind, Daniel H; Barres, Ben A; Paşca, Sergiu P

2015-07-01

The human cerebral cortex develops through an elaborate succession of cellular events that, when disrupted, can lead to neuropsychiatric disease. The ability to reprogram somatic cells into pluripotent cells that can be differentiated in vitro provides a unique opportunity to study normal and abnormal corticogenesis. Here, we present a simple and reproducible 3D culture approach for generating a laminated cerebral cortex-like structure, named human cortical spheroids (hCSs), from pluripotent stem cells. hCSs contain neurons from both deep and superficial cortical layers and map transcriptionally to in vivo fetal development. These neurons are electrophysiologically mature, display spontaneous activity, are surrounded by nonreactive astrocytes and form functional synapses. Experiments in acute hCS slices demonstrate that cortical neurons participate in network activity and produce complex synaptic events. These 3D cultures should allow a detailed interrogation of human cortical development, function and disease, and may prove a versatile platform for generating other neuronal and glial subtypes in vitro.

Frontal Cortex Activation Causes Rapid Plasticity of Auditory Cortical Processing

PubMed Central

Winkowski, Daniel E.; Bandyopadhyay, Sharba; Shamma, Shihab A.

2013-01-01

Neurons in the primary auditory cortex (A1) can show rapid changes in receptive fields when animals are engaged in sound detection and discrimination tasks. The source of a signal to A1 that triggers these changes is suspected to be in frontal cortical areas. How or whether activity in frontal areas can influence activity and sensory processing in A1 and the detailed changes occurring in A1 on the level of single neurons and in neuronal populations remain uncertain. Using electrophysiological techniques in mice, we found that pairing orbitofrontal cortex (OFC) stimulation with sound stimuli caused rapid changes in the sound-driven activity within A1 that are largely mediated by noncholinergic mechanisms. By integrating in vivo two-photon Ca2+ imaging of A1 with OFC stimulation, we found that pairing OFC activity with sounds caused dynamic and selective changes in sensory responses of neural populations in A1. Further, analysis of changes in signal and noise correlation after OFC pairing revealed improvement in neural population-based discrimination performance within A1. This improvement was frequency specific and dependent on correlation changes. These OFC-induced influences on auditory responses resemble behavior-induced influences on auditory responses and demonstrate that OFC activity could underlie the coordination of rapid, dynamic changes in A1 to dynamic sensory environments. PMID:24227723

Remembering the time: a continuous clock.

PubMed

Lewis, Penelope A; Miall, R Chris

2006-09-01

The neural mechanisms for time measurement are currently a subject of much debate. This article argues that our brains can measure time using the same dorsolateral prefrontal cells that are known to be involved in working memory. Evidence for this is: (1) the dorsolateral prefrontal cortex is integral to both cognitive timing and working memory; (2) both behavioural processes are modulated by dopamine and disrupted by manipulation of dopaminergic projections to the dorsolateral prefrontal cortex; (3) the neurons in question ramp their activity in a temporally predictable way during both types of processing; and (4) this ramping activity is modulated by dopamine. The dual involvement of these prefrontal neurons in working memory and cognitive timing supports a view of the prefrontal cortex as a multipurpose processor recruited by a wide variety of tasks.

Reward-dependent learning in neuronal networks for planning and decision making.

PubMed

Dehaene, S; Changeux, J P

2000-01-01

Neuronal network models have been proposed for the organization of evaluation and decision processes in prefrontal circuitry and their putative neuronal and molecular bases. The models all include an implementation and simulation of an elementary reward mechanism. Their central hypothesis is that tentative rules of behavior, which are coded by clusters of active neurons in prefrontal cortex, are selected or rejected based on an evaluation by this reward signal, which may be conveyed, for instance, by the mesencephalic dopaminergic neurons with which the prefrontal cortex is densely interconnected. At the molecular level, the reward signal is postulated to be a neurotransmitter such as dopamine, which exerts a global modulatory action on prefrontal synaptic efficacies, either via volume transmission or via targeted synaptic triads. Negative reinforcement has the effect of destabilizing the currently active rule-coding clusters; subsequently, spontaneous activity varies again from one cluster to another, giving the organism the chance to discover and learn a new rule. Thus, reward signals function as effective selection signals that either maintain or suppress currently active prefrontal representations as a function of their current adequacy. Simulations of this variation-selection have successfully accounted for the main features of several major tasks that depend on prefrontal cortex integrity, such as the delayed-response test, the Wisconsin card sorting test, the Tower of London test and the Stroop test. For the more complex tasks, we have found it necessary to supplement the external reward input with a second mechanism that supplies an internal reward; it consists of an auto-evaluation loop which short-circuits the reward input from the exterior. This allows for an internal evaluation of covert motor intentions without actualizing them as behaviors, by simply testing them covertly by comparison with memorized former experiences. This element of architecture gives access to enhanced rates of learning via an elementary process of internal or covert mental simulation. We have recently applied these ideas to a new model, developed with M. Kerszberg, which hypothesizes that prefrontal cortex and its reward-related connections contribute crucially to conscious effortful tasks. This model distinguishes two main computational spaces within the human brain: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative and attentional processors. We postulate that workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice; they selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously co-activated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. This model makes predictions concerning the spatio-temporal activation patterns during brain imaging of cognitive tasks, particularly concerning the conditions of activation of dorsolateral prefrontal cortex and anterior cingulate, their relation to reward mechanisms, and their specific reaction during error processing.

In Vitro, Ex Vivo and In Vivo Techniques to Study Neuronal Migration in the Developing Cerebral Cortex

PubMed Central

Azzarelli, Roberta; Oleari, Roberto; Lettieri, Antonella; Andre', Valentina; Cariboni, Anna

2017-01-01

Neuronal migration is a fundamental biological process that underlies proper brain development and neuronal circuit formation. In the developing cerebral cortex, distinct neuronal populations, producing excitatory, inhibitory and modulatory neurotransmitters, are generated in different germinative areas and migrate along various routes to reach their final positions within the cortex. Different technical approaches and experimental models have been adopted to study the mechanisms regulating neuronal migration in the cortex. In this review, we will discuss the most common in vitro, ex vivo and in vivo techniques to visualize and study cortical neuronal migration. PMID:28448448

Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

PubMed

Rudebeck, Peter H; Ripple, Joshua A; Mitz, Andrew R; Averbeck, Bruno B; Murray, Elisabeth A

2017-02-22

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus-reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards. Copyright © 2017 the authors 0270-6474/17/372186-17$15.00/0.

Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning

PubMed Central

Averbeck, Bruno B.

2017-01-01

Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also showed increased encoding of the instrumental responses that monkeys made on each trial. Behaviorally, changes in neural activity were accompanied by slower stimulus–reward learning. The findings suggest that interactions among amygdala, OFC, and MFC contribute to learning about stimuli that predict rewards. PMID:28123082

Population responses in primary auditory cortex simultaneously represent the temporal envelope and periodicity features in natural speech.

PubMed

Abrams, Daniel A; Nicol, Trent; White-Schwoch, Travis; Zecker, Steven; Kraus, Nina

2017-05-01

Speech perception relies on a listener's ability to simultaneously resolve multiple temporal features in the speech signal. Little is known regarding neural mechanisms that enable the simultaneous coding of concurrent temporal features in speech. Here we show that two categories of temporal features in speech, the low-frequency speech envelope and periodicity cues, are processed by distinct neural mechanisms within the same population of cortical neurons. We measured population activity in primary auditory cortex of anesthetized guinea pig in response to three variants of a naturally produced sentence. Results show that the envelope of population responses closely tracks the speech envelope, and this cortical activity more closely reflects wider bandwidths of the speech envelope compared to narrow bands. Additionally, neuronal populations represent the fundamental frequency of speech robustly with phase-locked responses. Importantly, these two temporal features of speech are simultaneously observed within neuronal ensembles in auditory cortex in response to clear, conversation, and compressed speech exemplars. Results show that auditory cortical neurons are adept at simultaneously resolving multiple temporal features in extended speech sentences using discrete coding mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain.

PubMed

Matsu-ura, Toru; Konishi, Yoshiyuki; Aoki, Tsutomu; Naranjo, Jose R; Mikoshiba, Katsuhiko; Tamura, Taka-aki

2002-12-30

Various transcriptional activators are induced in neurons concomitantly with long-lasting neural activity, whereas only a few transcription factors are known to act as neural activity-inducible transcription repressors. In this study, mRNA of DREAM (DRE-antagonizing modulator), a Ca(2+)-modulated transcriptional repressor, was demonstrated to accumulate in the mouse brain after pentylenetetrazol (PTZ)-induced seizures. Accumulation in the mouse hippocampus reached maximal level in the late phase (at 7-8 h) after PTZ injection. Kainic acid induced the same response. Interestingly, the late induction of DREAM expression required new protein synthesis and was blocked by MK801 suggesting that Ca(2+)-influx via NMDA receptors is necessary for the PTZ-mediated DREAM expression. In situ hybridization revealed that PTZ-induced DREAM mRNA accumulation was observed particularly in the dentate gyrus, cerebral cortex, and piriform cortex. The results of the present study demonstrate that DREAM is a neural activity-stimulated late gene and suggest its involvement in adaptation to long-lasting neuronal activity.

Spontaneously emerging direction selectivity maps in visual cortex through STDP.

PubMed

Wenisch, Oliver G; Noll, Joachim; Hemmen, J Leo van

2005-10-01

It is still an open question as to whether, and how, direction-selective neuronal responses in primary visual cortex are generated by feedforward thalamocortical or recurrent intracortical connections, or a combination of both. Here we present an investigation that concentrates on and, only for the sake of simplicity, restricts itself to intracortical circuits, in particular, with respect to the developmental aspects of direction selectivity through spike-timing-dependent synaptic plasticity. We show that directional responses can emerge in a recurrent network model of visual cortex with spiking neurons that integrate inputs mainly from a particular direction, thus giving rise to an asymmetrically shaped receptive field. A moving stimulus that enters the receptive field from this (preferred) direction will activate a neuron most strongly because of the increased number and/or strength of inputs from this direction and since delayed isotropic inhibition will neither overlap with, nor cancel excitation, as would be the case for other stimulus directions. It is demonstrated how direction-selective responses result from spatial asymmetries in the distribution of synaptic contacts or weights of inputs delivered to a neuron by slowly conducting intracortical axonal delay lines. By means of spike-timing-dependent synaptic plasticity with an asymmetric learning window this kind of coupling asymmetry develops naturally in a recurrent network of stochastically spiking neurons in a scenario where the neurons are activated by unidirectionally moving bar stimuli and even when only intrinsic spontaneous activity drives the learning process. We also present simulation results to show the ability of this model to produce direction preference maps similar to experimental findings.

Executive Control Over Cognition: Stronger and Earlier Rule-Based Modulation of Spatial Category Signals in Prefrontal Cortex Relative to Parietal Cortex

PubMed Central

Goodwin, Shikha J.; Blackman, Rachael K.; Sakellaridi, Sofia

2012-01-01

Human cognition is characterized by flexibility, the ability to select not only which action but which cognitive process to engage to best achieve the current behavioral objective. The ability to tailor information processing in the brain to rules, goals, or context is typically referred to as executive control, and although there is consensus that prefrontal cortex is importantly involved, at present we have an incomplete understanding of how computational flexibility is implemented at the level of prefrontal neurons and networks. To better understand the neural mechanisms of computational flexibility, we simultaneously recorded the electrical activity of groups of single neurons within prefrontal and posterior parietal cortex of monkeys performing a task that required executive control of spatial cognitive processing. In this task, monkeys applied different spatial categorization rules to reassign the same set of visual stimuli to alternative categories on a trial-by-trial basis. We found that single neurons were activated to represent spatially defined categories in a manner that was rule dependent, providing a physiological signature of a cognitive process that was implemented under executive control. We found also that neural signals coding rule-dependent categories were distributed between the parietal and prefrontal cortex—however, not equally. Rule-dependent category signals were stronger, more powerfully modulated by the rule, and earlier to emerge in prefrontal cortex relative to parietal cortex. This suggests that prefrontal cortex may initiate the switch in neural representation at a network level that is important for computational flexibility. PMID:22399773

The Population Tracking Model: A Simple, Scalable Statistical Model for Neural Population Data

PubMed Central

O'Donnell, Cian; alves, J. Tiago Gonç; Whiteley, Nick; Portera-Cailliau, Carlos; Sejnowski, Terrence J.

2017-01-01

Our understanding of neural population coding has been limited by a lack of analysis methods to characterize spiking data from large populations. The biggest challenge comes from the fact that the number of possible network activity patterns scales exponentially with the number of neurons recorded (∼2Neurons). Here we introduce a new statistical method for characterizing neural population activity that requires semi-independent fitting of only as many parameters as the square of the number of neurons, requiring drastically smaller data sets and minimal computation time. The model works by matching the population rate (the number of neurons synchronously active) and the probability that each individual neuron fires given the population rate. We found that this model can accurately fit synthetic data from up to 1000 neurons. We also found that the model could rapidly decode visual stimuli from neural population data from macaque primary visual cortex about 65 ms after stimulus onset. Finally, we used the model to estimate the entropy of neural population activity in developing mouse somatosensory cortex and, surprisingly, found that it first increases, and then decreases during development. This statistical model opens new options for interrogating neural population data and can bolster the use of modern large-scale in vivo Ca2+ and voltage imaging tools. PMID:27870612

Parvalbumin interneurons and calretinin fibers arising from the thalamic nucleus reuniens degenerate in the subiculum after kainic acid-induced seizures

PubMed Central

Drexel, M.; Preidt, A.P.; Kirchmair, E.; Sperk, G.

2011-01-01

The subiculum is the major output area of the hippocampus. It is closely interconnected with the entorhinal cortex and other parahippocampal areas. In animal models of temporal lobe epilepsy (TLE) and in TLE patients it exerts increased network excitability and may crucially contribute to the propagation of limbic seizures. Using immunohistochemistry and in situ-hybridization we now investigated neuropathological changes affecting parvalbumin and calretinin containing neurons in the subiculum and other parahippocampal areas after kainic acid-induced status epilepticus. We observed prominent losses in parvalbumin containing interneurons in the subiculum and entorhinal cortex, and in the principal cell layers of the pre- and parasubiculum. Degeneration of parvalbumin-positive neurons was associated with significant precipitation of parvalbumin-immunoreactive debris 24 h after kainic acid injection. In the subiculum the superficial portion of the pyramidal cell layer was more severely affected than its deep part. In the entorhinal cortex, the deep layers were more severely affected than the superficial ones. The decrease in number of parvalbumin-positive neurons in the subiculum and entorhinal cortex correlated with the number of spontaneous seizures subsequently experienced by the rats. The loss of parvalbumin neurons thus may contribute to the development of spontaneous seizures. On the other hand, surviving parvalbumin neurons revealed markedly increased expression of parvalbumin mRNA notably in the pyramidal cell layer of the subiculum and in all layers of the entorhinal cortex. This indicates increased activity of these neurons aiming to compensate for the partial loss of this functionally important neuron population. Furthermore, calretinin-positive fibers terminating in the molecular layer of the subiculum, in sector CA1 of the hippocampus proper and in the entorhinal cortex degenerated together with their presumed perikarya in the thalamic nucleus reuniens. In addition, a significant loss of calretinin containing interneurons was observed in the subiculum. Notably, the loss in parvalbumin positive neurons in the subiculum equaled that in human TLE. It may result in marked impairment of feed-forward inhibition of the temporo-ammonic pathway and may significantly contribute to epileptogenesis. Similarly, the loss of calretinin-positive fiber tracts originating from the nucleus reuniens thalami significantly contributes to the rearrangement of neuronal circuitries in the subiculum and entorhinal cortex during epileptogenesis. PMID:21616128

Emergent selectivity for task-relevant stimuli in higher-order auditory cortex

PubMed Central

Atiani, Serin; David, Stephen V.; Elgueda, Diego; Locastro, Michael; Radtke-Schuller, Susanne; Shamma, Shihab A.; Fritz, Jonathan B.

2014-01-01

A variety of attention-related effects have been demonstrated in primary auditory cortex (A1). However, an understanding of the functional role of higher auditory cortical areas in guiding attention to acoustic stimuli has been elusive. We recorded from neurons in two tonotopic cortical belt areas in the dorsal posterior ectosylvian gyrus (dPEG) of ferrets trained on a simple auditory discrimination task. Neurons in dPEG showed similar basic auditory tuning properties to A1, but during behavior we observed marked differences between these areas. In the belt areas, changes in neuronal firing rate and response dynamics greatly enhanced responses to target stimuli relative to distractors, allowing for greater attentional selection during active listening. Consistent with existing anatomical evidence, the pattern of sensory tuning and behavioral modulation in auditory belt cortex links the spectro-temporal representation of the whole acoustic scene in A1 to a more abstracted representation of task-relevant stimuli observed in frontal cortex. PMID:24742467

Long-range population dynamics of anatomically defined neocortical networks

PubMed Central

Chen, Jerry L; Voigt, Fabian F; Javadzadeh, Mitra; Krueppel, Roland; Helmchen, Fritjof

2016-01-01

The coordination of activity across neocortical areas is essential for mammalian brain function. Understanding this process requires simultaneous functional measurements across the cortex. In order to dissociate direct cortico-cortical interactions from other sources of neuronal correlations, it is furthermore desirable to target cross-areal recordings to neuronal subpopulations that anatomically project between areas. Here, we combined anatomical tracers with a novel multi-area two-photon microscope to perform simultaneous calcium imaging across mouse primary (S1) and secondary (S2) somatosensory whisker cortex during texture discrimination behavior, specifically identifying feedforward and feedback neurons. We find that coordination of S1-S2 activity increases during motor behaviors such as goal-directed whisking and licking. This effect was not specific to identified feedforward and feedback neurons. However, these mutually projecting neurons especially participated in inter-areal coordination when motor behavior was paired with whisker-texture touches, suggesting that direct S1-S2 interactions are sensory-dependent. Our results demonstrate specific functional coordination of anatomically-identified projection neurons across sensory cortices. DOI: http://dx.doi.org/10.7554/eLife.14679.001 PMID:27218452

Neuronal correlate of visual associative long-term memory in the primate temporal cortex

NASA Astrophysics Data System (ADS)

Miyashita, Yasushi

1988-10-01

In human long-term memory, ideas and concepts become associated in the learning process1. No neuronal correlate for this cognitive function has so far been described, except that memory traces are thought to be localized in the cerebral cortex; the temporal lobe has been assigned as the site for visual experience because electric stimulation of this area results in imagery recall,2 and lesions produce deficits in visual recognition of objects3-9. We previously reported that in the anterior ventral temporal cortex of monkeys, individual neurons have a sustained activity that is highly selective for a few of the 100 coloured fractal patterns used in a visual working-memory task10. Here I report the development of this selectivity through repeated trials involving the working memory. The few patterns for which a neuron was conjointly selective were frequently related to each other through stimulus-stimulus association imposed during training. The results indicate that the selectivity acquired by these cells represents a neuronal correlate of the associative long-term memory of pictures.

Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells.

PubMed

Safari, Mir-Shahram; Mirnajafi-Zadeh, Javad; Hioki, Hiroyuki; Tsumoto, Tadaharu

2017-10-06

Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex. It remains unclear whether there is any quantitative and functional difference between the PV → Pyr and SOM → Pyr connections. We compared unitary inhibitory postsynaptic currents (uIPSCs) evoked by electrophysiological activation of single presynaptic interneurons with population IPSCs evoked by photo-activation of a mass of interneurons in vivo and in vitro in transgenic mice in which PV or SOM neurons expressed channelrhodopsin-2, and found that at least about 14 PV neurons made strong connections with a postsynaptic Pyr cell while a much larger number of SOM neurons made weak connections. Activation or suppression of single PV neurons modified visual responses of postsynaptic Pyr cells in 6 of 7 pairs whereas that of single SOM neurons showed no significant modification in 8 of 11 pairs, suggesting that PV neurons can act solo whereas most of SOM neurons may act in chorus on Pyr cells.

Differential Activation of Fast-Spiking and Regular-Firing Neuron Populations During Movement and Reward in the Dorsal Medial Frontal Cortex

PubMed Central

Insel, Nathan; Barnes, Carol A.

2015-01-01

The medial prefrontal cortex is thought to be important for guiding behavior according to an animal's expectations. Efforts to decode the region have focused not only on the question of what information it computes, but also how distinct circuit components become engaged during behavior. We find that the activity of regular-firing, putative projection neurons contains rich information about behavioral context and firing fields cluster around reward sites, while activity among putative inhibitory and fast-spiking neurons is most associated with movement and accompanying sensory stimulation. These dissociations were observed even between adjacent neurons with apparently reciprocal, inhibitory–excitatory connections. A smaller population of projection neurons with burst-firing patterns did not show clustered firing fields around rewards; these neurons, although heterogeneous, were generally less selective for behavioral context than regular-firing cells. The data suggest a network that tracks an animal's behavioral situation while, at the same time, regulating excitation levels to emphasize high valued positions. In this scenario, the function of fast-spiking inhibitory neurons is to constrain network output relative to incoming sensory flow. This scheme could serve as a bridge between abstract sensorimotor information and single-dimensional codes for value, providing a neural framework to generate expectations from behavioral state. PMID:24700585

Role of the Functional State of the Hypothalamus in Bioelectric Reactions of the Cerebral Cortex to Radiation,

DTIC Science & Technology

The effect of subjection of the hypothalamus to electrocoagulation in the area of the mamillary bodies on the bioelectric activity and reactivity of...the cerebral cortex exposed to radiation was studied. Rabbits were irradiated on the 10th day after electrocoagulation . Immediately after... electrocoagulation , a decline in the excitability and functional activity of cortical neurons in the posterior section of the cortex and a decrease in the

Quantitative distribution of GABA-immunoreactive neurons in cetacean visual cortex is similar to that in land mammals.

PubMed

Garey, L J; Takács, J; Revishchin, A V; Hámori, J

1989-04-24

Sections of the anterior portion of the visual cortex in the lateral gyrus of the Black Sea porpoise were studied to determine the neuronal architecture and numerical density, and the distribution of neurons immunoreactive to gamma-aminobutyric acid (GABA). Cytoarchitecture and neuronal density are similar to those described in another cetacean, the bottlenose dolphin. GABA-positive neurons are distributed through all layers of the visual cortex but are especially dense in layers II and III, and comprise some 20% of the total neuronal population in this part of the cortex. The distribution of GABA-positive neurons is similar to that found in land mammals.

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

PubMed

Lo, Fu-Sun; Erzurumlu, Reha S; Powell, Elizabeth M

2016-03-30

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. Copyright © 2016 the authors 0270-6474/16/363691-07$15.00/0.

Active integration of glutamatergic input to the inferior olive generates bidirectional postsynaptic potentials

PubMed Central

Garden, Derek L. F.; Rinaldi, Arianna

2016-01-01

Key points We establish experimental preparations for optogenetic investigation of glutamatergic input to the inferior olive.Neurones in the principal olivary nucleus receive monosynaptic extra‐somatic glutamatergic input from the neocortex.Glutamatergic inputs to neurones in the inferior olive generate bidirectional postsynaptic potentials (PSPs), with a fast excitatory component followed by a slower inhibitory component.Small conductance calcium‐activated potassium (SK) channels are required for the slow inhibitory component of glutamatergic PSPs and oppose temporal summation of inputs at intervals ≤ 20 ms.Active integration of synaptic input within the inferior olive may play a central role in control of olivo‐cerebellar climbing fibre signals. Abstract The inferior olive plays a critical role in motor coordination and learning by integrating diverse afferent signals to generate climbing fibre inputs to the cerebellar cortex. While it is well established that climbing fibre signals are important for motor coordination, the mechanisms by which neurones in the inferior olive integrate synaptic inputs and the roles of particular ion channels are unclear. Here, we test the hypothesis that neurones in the inferior olive actively integrate glutamatergic synaptic inputs. We demonstrate that optogenetically activated long‐range synaptic inputs to the inferior olive, including projections from the motor cortex, generate rapid excitatory potentials followed by slower inhibitory potentials. Synaptic projections from the motor cortex preferentially target the principal olivary nucleus. We show that inhibitory and excitatory components of the bidirectional synaptic potentials are dependent upon AMPA (GluA) receptors, are GABAA independent, and originate from the same presynaptic axons. Consistent with models that predict active integration of synaptic inputs by inferior olive neurones, we find that the inhibitory component is reduced by blocking large conductance calcium‐activated potassium channels with iberiotoxin, and is abolished by blocking small conductance calcium‐activated potassium channels with apamin. Summation of excitatory components of synaptic responses to inputs at intervals ≤ 20 ms is increased by apamin, suggesting a role for the inhibitory component of glutamatergic responses in temporal integration. Our results indicate that neurones in the inferior olive implement novel rules for synaptic integration and suggest new principles for the contribution of inferior olive neurones to coordinated motor behaviours. PMID:27767209

Functional signature of recovering cortex: dissociation of local field potentials and spiking activity in somatosensory cortices of spinal cord injured monkeys.

PubMed

Wang, Zheng; Qi, Hui-Xin; Kaas, Jon H; Roe, Anna W; Chen, Li Min

2013-11-01

After disruption of dorsal column afferents at high cervical spinal levels in adult monkeys, somatosensory cortical neurons recover responsiveness to tactile stimulation of the hand; this reactivation correlates with a recovery of hand use. However, it is not known if all neuronal response properties recover, and whether different cortical areas recover in a similar manner. To address this, we recorded neuronal activity in cortical area 3b and S2 in adult squirrel monkeys weeks after unilateral lesion of the dorsal columns. We found that in response to vibrotactile stimulation, local field potentials remained robust at all frequency ranges. However, neuronal spiking activity failed to follow at high frequencies (≥15 Hz). We suggest that the failure to generate spiking activity at high stimulus frequency reflects a changed balance of inhibition and excitation in both area 3b and S2, and that this mismatch in spiking and local field potential is a signature of an early phase of recovering cortex (

Elevated correlations in neuronal ensembles of mouse auditory cortex following parturition.

PubMed

Rothschild, Gideon; Cohen, Lior; Mizrahi, Adi; Nelken, Israel

2013-07-31

The auditory cortex is malleable by experience. Previous studies of auditory plasticity have described experience-dependent changes in response profiles of single neurons or changes in global tonotopic organization. However, experience-dependent changes in the dynamics of local neural populations have remained unexplored. In this study, we examined the influence of a dramatic yet natural experience in the life of female mice, giving birth and becoming a mother on single neurons and neuronal ensembles in the primary auditory cortex (A1). Using in vivo two-photon calcium imaging and electrophysiological recordings from layer 2/3 in A1 of mothers and age-matched virgin mice, we monitored changes in the responses to a set of artificial and natural sounds. Population dynamics underwent large changes as measured by pairwise and higher-order correlations, with noise correlations increasing as much as twofold in lactating mothers. Concomitantly, changes in response properties of single neurons were modest and selective. Remarkably, despite the large changes in correlations, information about stimulus identity remained essentially the same in the two groups. Our results demonstrate changes in the correlation structure of neuronal activity as a result of a natural life event.

Background sounds contribute to spectrotemporal plasticity in primary auditory cortex

PubMed Central

Moucha, Raluca; Pandya, Pritesh K.; Engineer, Navzer D.; Rathbun, Daniel L.

2010-01-01

The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8–4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity PMID:15616812

Neurons in Anterior Cingulate Cortex Multiplex Information about Reward and Action

PubMed Central

Hayden, Benjamin Y.; Platt, Michael L.

2010-01-01

The dorsal anterior cingulate cortex (dACC) is thought to play a critical role in forming associations between rewards and actions. Currently available physiological data, however, remain inconclusive regarding the question of whether dACC neurons carry information linking particular actions to reward or, instead, encode abstract reward information independent of specific actions. Here we show that firing rates of a majority of dACC neurons in a population studied in an eight-option variably rewarded choice task were sensitive to both saccade direction and reward value. Furthermore, the influences of reward and saccade direction on neuronal activity were roughly equal in magnitude over the range of rewards tested and were statistically independent. Our results indicate that dACC neurons multiplex information about both reward and action, endorsing the idea that this area links motivational outcomes to behavior and undermining the notion that its neurons solely contribute to reward processing in the abstract. PMID:20203193

Spike-Timing of Orbitofrontal Neurons Is Synchronized With Breathing.

PubMed

Kőszeghy, Áron; Lasztóczi, Bálint; Forro, Thomas; Klausberger, Thomas

2018-01-01

The orbitofrontal cortex (OFC) has been implicated in a multiplicity of complex brain functions, including representations of expected outcome properties, post-decision confidence, momentary food-reward values, complex flavors and odors. As breathing rhythm has an influence on odor processing at primary olfactory areas, we tested the hypothesis that it may also influence neuronal activity in the OFC, a prefrontal area involved also in higher order processing of odors. We recorded spike timing of orbitofrontal neurons as well as local field potentials (LFPs) in awake, head-fixed mice, together with the breathing rhythm. We observed that a large majority of orbitofrontal neurons showed robust phase-coupling to breathing during immobility and running. The phase coupling of action potentials to breathing was significantly stronger in orbitofrontal neurons compared to cells in the medial prefrontal cortex. The characteristic synchronization of orbitofrontal neurons with breathing might provide a temporal framework for multi-variable processing of olfactory, gustatory and reward-value relationships.

Responses in Rat Core Auditory Cortex are Preserved during Sleep Spindle Oscillations

PubMed Central

Sela, Yaniv; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Tononi, Giulio; Nir, Yuval

2016-01-01

Study Objectives: Sleep is defined as a reversible state of reduction in sensory responsiveness and immobility. A long-standing hypothesis suggests that a high arousal threshold during non-rapid eye movement (NREM) sleep is mediated by sleep spindle oscillations, impairing thalamocortical transmission of incoming sensory stimuli. Here we set out to test this idea directly by examining sensory-evoked neuronal spiking activity during natural sleep. Methods: We compared neuronal (n = 269) and multiunit activity (MUA), as well as local field potentials (LFP) in rat core auditory cortex (A1) during NREM sleep, comparing responses to sounds depending on the presence or absence of sleep spindles. Results: We found that sleep spindles robustly modulated the timing of neuronal discharges in A1. However, responses to sounds were nearly identical for all measured signals including isolated neurons, MUA, and LFPs (all differences < 10%). Furthermore, in 10% of trials, auditory stimulation led to an early termination of the sleep spindle oscillation around 150–250 msec following stimulus onset. Finally, active ON states and inactive OFF periods during slow waves in NREM sleep affected the auditory response in opposite ways, depending on stimulus intensity. Conclusions: Responses in core auditory cortex are well preserved regardless of sleep spindles recorded in that area, suggesting that thalamocortical sensory relay remains functional during sleep spindles, and that sensory disconnection in sleep is mediated by other mechanisms. Citation: Sela Y, Vyazovskiy VV, Cirelli C, Tononi G, Nir Y. Responses in rat core auditory cortex are preserved during sleep spindle oscillations. SLEEP 2016;39(5):1069–1082. PMID:26856904

Multiplicative and additive modulation of neuronal tuning with population activity affects encoded information

PubMed Central

Arandia-Romero, Iñigo; Tanabe, Seiji; Drugowitsch, Jan; Kohn, Adam; Moreno-Bote, Rubén

2016-01-01

Numerous studies have shown that neuronal responses are modulated by stimulus properties, and also by the state of the local network. However, little is known about how activity fluctuations of neuronal populations modulate the sensory tuning of cells and affect their encoded information. We found that fluctuations in ongoing and stimulus-evoked population activity in primate visual cortex modulate the tuning of neurons in a multiplicative and additive manner. While distributed on a continuum, neurons with stronger multiplicative effects tended to have less additive modulation, and vice versa. The information encoded by multiplicatively-modulated neurons increased with greater population activity, while that of additively-modulated neurons decreased. These effects offset each other, so that population activity had little effect on total information. Our results thus suggest that intrinsic activity fluctuations may act as a `traffic light' that determines which subset of neurons are most informative. PMID:26924437

Role of the medial prefrontal cortex in cataplexy.

PubMed

Oishi, Yo; Williams, Rhiannan H; Agostinelli, Lindsay; Arrigoni, Elda; Fuller, Patrick M; Mochizuki, Takatoshi; Saper, Clifford B; Scammell, Thomas E

2013-06-05

Narcolepsy is characterized by chronic sleepiness and cataplexy, episodes of profound muscle weakness that are often triggered by strong, positive emotions. Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which positive emotions trigger cataplexy. Using orexin knock-out mice as a model of narcolepsy, we found that palatable foods, especially chocolate, markedly increased cataplexy and activated neurons in the medial prefrontal cortex (mPFC). Reversible suppression of mPFC activity using an engineered chloride channel substantially reduced cataplexy induced by chocolate but did not affect spontaneous cataplexy. In addition, neurons in the mPFC innervated parts of the amygdala and lateral hypothalamus that contain neurons active during cataplexy and that innervate brainstem regions known to regulate motor tone. These observations indicate that the mPFC is a critical site through which positive emotions trigger cataplexy.

Role of the medial prefrontal cortex in cataplexy

PubMed Central

Oishi, Yo; Williams, Rhiannan H.; Agostinelli, Lindsay; Arrigoni, Elda; Fuller, Patrick M.; Mochizuki, Takatoshi; Saper, Clifford B.; Scammell, Thomas E.

2013-01-01

Narcolepsy is characterized by chronic sleepiness and cataplexy - episodes of profound muscle weakness that are often triggered by strong, positive emotions. Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which positive emotions trigger cataplexy. Using orexin knockout mice as a model of narcolepsy, we found that palatable foods, especially chocolate, markedly increased cataplexy and activated neurons in the medial prefrontal cortex (mPFC). Reversible suppression of mPFC activity using an engineered chloride channel substantially reduced cataplexy induced by chocolate but did not affect spontaneous cataplexy. In addition, neurons in the mPFC innervated parts of the amygdala and lateral hypothalamus that contain neurons active during cataplexy, and that innervate brainstem regions known to regulate motor tone. These observations indicate that the mPFC is a critical site through which positive emotions trigger cataplexy. PMID:23739971

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

PubMed

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2016-01-01

Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Common inputs in subthreshold membrane potential: The role of quiescent states in neuronal activity

NASA Astrophysics Data System (ADS)

Montangie, Lisandro; Montani, Fernando

2018-06-01

Experiments in certain regions of the cerebral cortex suggest that the spiking activity of neuronal populations is regulated by common non-Gaussian inputs across neurons. We model these deviations from random-walk processes with q -Gaussian distributions into simple threshold neurons, and investigate the scaling properties in large neural populations. We show that deviations from the Gaussian statistics provide a natural framework to regulate population statistics such as sparsity, entropy, and specific heat. This type of description allows us to provide an adequate strategy to explain the information encoding in the case of low neuronal activity and its possible implications on information transmission.

Predominance of Movement Speed Over Direction in Neuronal Population Signals of Motor Cortex: Intracranial EEG Data and A Simple Explanatory Model

PubMed Central

Hammer, Jiří; Pistohl, Tobias; Fischer, Jörg; Kršek, Pavel; Tomášek, Martin; Marusič, Petr; Schulze-Bonhage, Andreas; Aertsen, Ad; Ball, Tonio

2016-01-01

How neuronal activity of motor cortex is related to movement is a central topic in motor neuroscience. Motor-cortical single neurons are more closely related to hand movement velocity than speed, that is, the magnitude of the (directional) velocity vector. Recently, there is also increasing interest in the representation of movement parameters in neuronal population activity, such as reflected in the intracranial EEG (iEEG). We show that in iEEG, contrasting to what has been previously found on the single neuron level, speed predominates over velocity. The predominant speed representation was present in nearly all iEEG signal features, up to the 600–1000 Hz range. Using a model of motor-cortical signals arising from neuronal populations with realistic single neuron tuning properties, we show how this reversal can be understood as a consequence of increasing population size. Our findings demonstrate that the information profile in large population signals may systematically differ from the single neuron level, a principle that may be helpful in the interpretation of neuronal population signals in general, including, for example, EEG and functional magnetic resonance imaging. Taking advantage of the robust speed population signal may help in developing brain–machine interfaces exploiting population signals. PMID:26984895

Distribution of neurons in functional areas of the mouse cerebral cortex reveals quantitatively different cortical zones

PubMed Central

Herculano-Houzel, Suzana; Watson, Charles; Paxinos, George

2013-01-01

How are neurons distributed along the cortical surface and across functional areas? Here we use the isotropic fractionator (Herculano-Houzel and Lent, 2005) to analyze the distribution of neurons across the entire isocortex of the mouse, divided into 18 functional areas defined anatomically. We find that the number of neurons underneath a surface area (the N/A ratio) varies 4.5-fold across functional areas and neuronal density varies 3.2-fold. The face area of S1 contains the most neurons, followed by motor cortex and the primary visual cortex. Remarkably, while the distribution of neurons across functional areas does not accompany the distribution of surface area, it mirrors closely the distribution of cortical volumes—with the exception of the visual areas, which hold more neurons than expected for their volume. Across the non-visual cortex, the volume of individual functional areas is a shared linear function of their number of neurons, while in the visual areas, neuronal densities are much higher than in all other areas. In contrast, the 18 functional areas cluster into three different zones according to the relationship between the N/A ratio and cortical thickness and neuronal density: these three clusters can be called visual, sensory, and, possibly, associative. These findings are remarkably similar to those in the human cerebral cortex (Ribeiro et al., 2013) and suggest that, like the human cerebral cortex, the mouse cerebral cortex comprises two zones that differ in how neurons form the cortical volume, and three zones that differ in how neurons are distributed underneath the cortical surface, possibly in relation to local differences in connectivity through the white matter. Our results suggest that beyond the developmental divide into visual and non-visual cortex, functional areas initially share a common distribution of neurons along the parenchyma that become delimited into functional areas according to the pattern of connectivity established later. PMID:24155697

The activation of metabotropic glutamate 5 receptors in the rat ventral tegmental area increases dopamine extracellular levels.

PubMed

Ferrada, Carla; Sotomayor-Zárate, Ramón; Abarca, Jorge; Gysling, Katia

2017-01-01

The mesocorticolimbic circuit projects to the prefrontal cortex, hippocampus, amygdala, and nucleus accumbens, among others, and it originates in the dopaminergic neurons of the ventral tegmental area (VTA). The VTA receives glutamatergic inputs from the prefrontal cortex and several subcortical regions. The glutamate released activates dopaminergic neurons and its action depends on the activation of ionotropic and metabotropic glutamate receptors. VTA dopaminergic neurons release dopamine (DA) from axon terminals in the innervated regions and somatodendritically in the VTA itself. DA release in the VTA is directly correlated with the activity of dopaminergic neurons. We hypothesized that metabotropic glutamate 5 receptors (mGlu5) directly regulate the activity of VTA dopaminergic neurons. To test this hypothesis, the extracellular levels of VTA DA and glutamate were studied by in-vivo microdialysis after an intra-VTA perfusion of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), selective mGlu5 agonist. We observed that CHPG induced a significant increase in VTA DA and glutamate extracellular levels. To determine whether the effect of CHPG on DA levels is because of the increase in glutamate release, we perfused kynurenic acid, an ionotropic glutamate receptor antagonist, through the probe. Our results showed that kynurenic acid did not block the ability of CHPG to cause DA release. Thus, our results suggest that CHPG acts directly on mGlu5 in dopaminergic neurons to induce the release of DA.

Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

PubMed

McCarthy, Deirdre M; Bhide, Pradeep G

2012-01-01

Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

Heterosynaptic modulation of evoked synaptic potentials in layer II of the entorhinal cortex by activation of the parasubiculum

PubMed Central

Sparks, Daniel W.

2016-01-01

The superficial layers of the entorhinal cortex receive sensory and associational cortical inputs and provide the hippocampus with the majority of its cortical sensory input. The parasubiculum, which receives input from multiple hippocampal subfields, sends its single major output projection to layer II of the entorhinal cortex, suggesting that it may modulate processing of synaptic inputs to the entorhinal cortex. Indeed, stimulation of the parasubiculum can enhance entorhinal responses to synaptic input from the piriform cortex in vivo. Theta EEG activity contributes to spatial and mnemonic processes in this region, and the current study assessed how stimulation of the parasubiculum with either single pulses or short, five-pulse, theta-frequency trains may modulate synaptic responses in layer II entorhinal stellate neurons evoked by stimulation of layer I afferents in vitro. Parasubicular stimulation pulses or trains suppressed responses to layer I stimulation at intervals of 5 ms, and parasubicular stimulation trains facilitated layer I responses at a train-pulse interval of 25 ms. This suggests that firing of parasubicular neurons during theta activity may heterosynaptically enhance incoming sensory inputs to the entorhinal cortex. Bath application of the hyperpolarization-activated cation current (Ih) blocker ZD7288 enhanced the facilitation effect, suggesting that cholinergic inhibition of Ih may contribute. In addition, repetitive pairing of parasubicular trains and layer I stimulation induced a lasting depression of entorhinal responses to layer I stimulation. These findings provide evidence that theta activity in the parasubiculum may promote heterosynaptic modulation effects that may alter sensory processing in the entorhinal cortex. PMID:27146979

Neuronal Categorization and Discrimination of Social Behaviors in Primate Prefrontal Cortex

PubMed Central

Tsunada, Joji; Sawaguchi, Toshiyuki

2012-01-01

It has been implied that primates have an ability to categorize social behaviors between other individuals for the execution of adequate social-interactions. Since the lateral prefrontal cortex (LPFC) is involved in both the categorization and the processing of social information, the primate LPFC may be involved in the categorization of social behaviors. To test this hypothesis, we examined neuronal activity in the LPFC of monkeys during presentations of two types of movies of social behaviors (grooming, mounting) and movies of plural monkeys without any eye- or body-contacts between them (no-contacts movies). Although the monkeys were not required to categorize and discriminate the movies in this task, a subset of neurons sampled from the LPFC showed a significantly different activity during the presentation of a specific type of social behaviors in comparison with the others. These neurons categorized social behaviors at the population level and, at the individual neuron level, the majority of the neurons discriminated each movie within the same category of social behaviors. Our findings suggest that a fraction of LPFC neurons process categorical and discriminative information of social behaviors, thereby contributing to the adaptation to social environments. PMID:23285110

Nicotine Modulates Multiple Regions in the Limbic Stress Network Regulating Activation of Hypophysiotrophic Neurons in Hypothalamic Paraventricular Nucleus

PubMed Central

Yu, Guoliang; Sharp, Burt M.

2012-01-01

Nicotine intake affects CNS responses to stressors. We reported that nicotine self-administration (SA) augmented the hypothalamo-pituitary-adrenal (HPA) stress response, in part due to altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic-PVN interactions involving medial prefrontal cortex, amygdala, bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress-induced neuronal activation in limbic-PVN network, using c-Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress-induced c-Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri-PVN; but increased c-Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro-gold (FG) was injected into avBST or PVN, since GABAergic neurons in avBST projecting to PVN corticotrophin-releasing factor (CRF) neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress-induced c-Fos expression in retrograde-labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic-PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic-BST-PVN interactions underlying the disinhibition of PVN CRF neurons, an essential component of the amplified HPA response to stress by nicotine. PMID:22578217

Cerebral morphology and functional sparing after prenatal frontal cortex lesions in rats.

PubMed

Kolb, B; Cioe, J; Muirhead, D

1998-03-01

Rats were given suction lesions of the presumptive frontal cortex on embryonic day 18 (E18) and subsequently tested, as adults, on tests of spatial navigation (Morris water task, radial arm maze), motor tasks (Whishaw reaching task, beam walking), and locomotor activity. Frontal cortical lesions at E18 affected cerebral morphogenesis, producing unusual morphological structures including abnormal patches of neurons in the cortex and white matter as well as neuronal bridges between the hemispheres. A small sample of E18 operates also had hydrocephaly. The animals with E18 lesions without hydrocephalus were behaviorally indistinguishable from littermate controls. The results demonstrate that animals with focal lesions of the presumptive frontal cortex have gross abnormalities in cerebral morphology but the lesions leave the functions normally subserved by the frontal cortex in adult rats unaffected. The results are discussed in the context of a hypothesis regarding the optimal times for functional recovery from cortical injury.

A Synaptic Basis for Memory Storage in the Cerebral Cortex

NASA Astrophysics Data System (ADS)

Bear, Mark F.

1996-11-01

A cardinal feature of neurons in the cerebral cortex is stimulus selectivity, and experience-dependent shifts in selectivity are a common correlate of memory formation. We have used a theoretical ``learning rule,'' devised to account for experience-dependent shifts in neuronal selectivity, to guide experiments on the elementary mechanisms of synaptic plasticity in hippocampus and neocortex. These experiments reveal that many synapses in hippocampus and neocortex are bidirectionally modifiable, that the modifications persist long enough to contribute to long-term memory storage, and that key variables governing the sign of synaptic plasticity are the amount of NMDA receptor activation and the recent history of cortical activity.

Learning enhances the relative impact of top-down processing in the visual cortex

PubMed Central

Makino, Hiroshi; Komiyama, Takaki

2015-01-01

Theories have proposed that in sensory cortices learning can enhance top-down modulation by higher brain areas while reducing bottom-up sensory inputs. To address circuit mechanisms underlying this process, we examined the activity of layer 2/3 (L2/3) excitatory neurons in the mouse primary visual cortex (V1) as well as L4 neurons, the main bottom-up source, and long-range top-down projections from the retrosplenial cortex (RSC) during associative learning over days using chronic two-photon calcium imaging. During learning, L4 responses gradually weakened, while RSC inputs became stronger. Furthermore, L2/3 acquired a ramp-up response temporal profile with learning, coinciding with a similar change in RSC inputs. Learning also reduced the activity of somatostatin-expressing inhibitory neurons (SOM-INs) in V1 that could potentially gate top-down inputs. Finally, RSC inactivation or SOM-IN activation was sufficient to partially reverse the learning-induced changes in L2/3. Together, these results reveal a learning-dependent dynamic shift in the balance between bottom-up and top-down information streams and uncover a role of SOM-INs in controlling this process. PMID:26167904

Inhibitory Gating of Basolateral Amygdala Inputs to the Prefrontal Cortex

PubMed Central

McGarry, Laura M.

2016-01-01

Interactions between the prefrontal cortex (PFC) and basolateral amygdala (BLA) regulate emotional behaviors. However, a circuit-level understanding of functional connections between these brain regions remains incomplete. The BLA sends prominent glutamatergic projections to the PFC, but the overall influence of these inputs is predominantly inhibitory. Here we combine targeted recordings and optogenetics to examine the synaptic underpinnings of this inhibition in the mouse infralimbic PFC. We find that BLA inputs preferentially target layer 2 corticoamygdala over neighboring corticostriatal neurons. However, these inputs make even stronger connections onto neighboring parvalbumin and somatostatin expressing interneurons. Inhibitory connections from these two populations of interneurons are also much stronger onto corticoamygdala neurons. Consequently, BLA inputs are able to drive robust feedforward inhibition via two parallel interneuron pathways. Moreover, the contributions of these interneurons shift during repetitive activity, due to differences in short-term synaptic dynamics. Thus, parvalbumin interneurons are activated at the start of stimulus trains, whereas somatostatin interneuron activation builds during these trains. Together, these results reveal how the BLA impacts the PFC through a complex interplay of direct excitation and feedforward inhibition. They also highlight the roles of targeted connections onto multiple projection neurons and interneurons in this cortical circuit. Our findings provide a mechanistic understanding for how the BLA can influence the PFC circuit, with important implications for how this circuit participates in the regulation of emotion. SIGNIFICANCE STATEMENT The prefrontal cortex (PFC) and basolateral amygdala (BLA) interact to control emotional behaviors. Here we show that BLA inputs elicit direct excitation and feedforward inhibition of layer 2 projection neurons in infralimbic PFC. BLA inputs are much stronger at corticoamygdala neurons compared with nearby corticostriatal neurons. However, these inputs are even more powerful at parvalbumin and somatostatin expressing interneurons. BLA inputs thus activate two parallel inhibitory networks, whose contributions change during repetitive activity. Finally, connections from these interneurons are also more powerful at corticoamygdala neurons compared with corticostriatal neurons. Together, our results demonstrate how the BLA predominantly inhibits the PFC via a complex sequence involving multiple cell-type and input-specific connections. PMID:27605614

Inhibitory Gating of Basolateral Amygdala Inputs to the Prefrontal Cortex.

PubMed

McGarry, Laura M; Carter, Adam G

2016-09-07

Interactions between the prefrontal cortex (PFC) and basolateral amygdala (BLA) regulate emotional behaviors. However, a circuit-level understanding of functional connections between these brain regions remains incomplete. The BLA sends prominent glutamatergic projections to the PFC, but the overall influence of these inputs is predominantly inhibitory. Here we combine targeted recordings and optogenetics to examine the synaptic underpinnings of this inhibition in the mouse infralimbic PFC. We find that BLA inputs preferentially target layer 2 corticoamygdala over neighboring corticostriatal neurons. However, these inputs make even stronger connections onto neighboring parvalbumin and somatostatin expressing interneurons. Inhibitory connections from these two populations of interneurons are also much stronger onto corticoamygdala neurons. Consequently, BLA inputs are able to drive robust feedforward inhibition via two parallel interneuron pathways. Moreover, the contributions of these interneurons shift during repetitive activity, due to differences in short-term synaptic dynamics. Thus, parvalbumin interneurons are activated at the start of stimulus trains, whereas somatostatin interneuron activation builds during these trains. Together, these results reveal how the BLA impacts the PFC through a complex interplay of direct excitation and feedforward inhibition. They also highlight the roles of targeted connections onto multiple projection neurons and interneurons in this cortical circuit. Our findings provide a mechanistic understanding for how the BLA can influence the PFC circuit, with important implications for how this circuit participates in the regulation of emotion. The prefrontal cortex (PFC) and basolateral amygdala (BLA) interact to control emotional behaviors. Here we show that BLA inputs elicit direct excitation and feedforward inhibition of layer 2 projection neurons in infralimbic PFC. BLA inputs are much stronger at corticoamygdala neurons compared with nearby corticostriatal neurons. However, these inputs are even more powerful at parvalbumin and somatostatin expressing interneurons. BLA inputs thus activate two parallel inhibitory networks, whose contributions change during repetitive activity. Finally, connections from these interneurons are also more powerful at corticoamygdala neurons compared with corticostriatal neurons. Together, our results demonstrate how the BLA predominantly inhibits the PFC via a complex sequence involving multiple cell-type and input-specific connections. Copyright © 2016 the authors 0270-6474/16/369391-16$15.00/0.

Laminar- and Target-Specific Amygdalar Inputs in Rat Primary Gustatory Cortex.

PubMed

Haley, Melissa S; Fontanini, Alfredo; Maffei, Arianna

2016-03-02

The primary gustatory cortex (GC) receives projections from the basolateral nucleus of the amygdala (BLA). Behavioral and electrophysiological studies demonstrated that this projection is involved in encoding the hedonic value of taste and is a source of anticipatory activity in GC. Anatomically, this projection is largest in the agranular portion of GC; however, its synaptic targets and synaptic properties are currently unknown. In vivo electrophysiological recordings report conflicting evidence about BLA afferents either selectively activating excitatory neurons or driving a compound response consistent with the activation of inhibitory circuits. Here we demonstrate that BLA afferents directly activate excitatory neurons and two distinct populations of inhibitory neurons in both superficial and deep layers of rat GC. BLA afferents recruit different proportions of excitatory and inhibitory neurons and show distinct patterns of circuit activation in the superficial and deep layers of GC. These results provide the first circuit-level analysis of BLA inputs to a sensory area. Laminar- and target-specific differences of BLA inputs likely explain the complexity of amygdalocortical interactions during sensory processing. Projections from the basolateral nucleus of the amygdala (BLA) to the cortex convey information about the emotional value and the expectation of a sensory stimulus. Although much work has been done to establish the behavioral role of BLA inputs to sensory cortices, very little is known about the circuit organization of BLA projections. Here we provide the first in-depth analysis of connectivity and synaptic properties of the BLA input to the gustatory cortex. We show that BLA afferents activate excitatory and inhibitory circuits in a layer-specific and pattern-specific manner. Our results provide important new information about how neural circuits establishing the hedonic value of sensory stimuli and driving anticipatory behaviors are organized at the synaptic level. Copyright © 2016 the authors 0270-6474/16/362623-15$15.00/0.

High baseline activity in inferior temporal cortex improves neural and behavioral discriminability during visual categorization

PubMed Central

Emadi, Nazli; Rajimehr, Reza; Esteky, Hossein

2014-01-01

Spontaneous firing is a ubiquitous property of neural activity in the brain. Recent literature suggests that this baseline activity plays a key role in perception. However, it is not known how the baseline activity contributes to neural coding and behavior. Here, by recording from the single neurons in the inferior temporal cortex of monkeys performing a visual categorization task, we thoroughly explored the relationship between baseline activity, the evoked response, and behavior. Specifically we found that a low-frequency (<8 Hz) oscillation in the spike train, prior and phase-locked to the stimulus onset, was correlated with increased gamma power and neuronal baseline activity. This enhancement of the baseline activity was then followed by an increase in the neural selectivity and the response reliability and eventually a higher behavioral performance. PMID:25404900

Predictive cues for auditory stream formation in humans and monkeys.

PubMed

Aggelopoulos, Nikolaos C; Deike, Susann; Selezneva, Elena; Scheich, Henning; Brechmann, André; Brosch, Michael

2017-12-18

Auditory perception is improved when stimuli are predictable, and this effect is evident in a modulation of the activity of neurons in the auditory cortex as shown previously. Human listeners can better predict the presence of duration deviants embedded in stimulus streams with fixed interonset interval (isochrony) and repeated duration pattern (regularity), and neurons in the auditory cortex of macaque monkeys have stronger sustained responses in the 60-140 ms post-stimulus time window under these conditions. Subsequently, the question has arisen whether isochrony or regularity in the sensory input contributed to the enhancement of the neuronal and behavioural responses. Therefore, we varied the two factors isochrony and regularity independently and measured the ability of human subjects to detect deviants embedded in these sequences as well as measuring the responses of neurons the primary auditory cortex of macaque monkeys during presentations of the sequences. The performance of humans in detecting deviants was significantly increased by regularity. Isochrony enhanced detection only in the presence of the regularity cue. In monkeys, regularity increased the sustained component of neuronal tone responses in auditory cortex while isochrony had no consistent effect. Although both regularity and isochrony can be considered as parameters that would make a sequence of sounds more predictable, our results from the human and monkey experiments converge in that regularity has a greater influence on behavioural performance and neuronal responses. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Striatal dysfunction increases basal ganglia output during motor cortex activation in parkinsonian rats.

PubMed

Belluscio, Mariano A; Riquelme, Luis A; Murer, M Gustavo

2007-05-01

During movement, inhibitory neurons in the basal ganglia output nuclei show complex modulations of firing, which are presumptively driven by corticostriatal and corticosubthalamic input. Reductions in discharge should facilitate movement by disinhibiting thalamic and brain stem nuclei while increases would do the opposite. A proposal that nigrostriatal dopamine pathway degeneration disrupts trans-striatal pathways' balance resulting in sustained overactivity of basal ganglia output nuclei neurons and Parkinson's disease clinical signs is not fully supported by experimental evidence, which instead shows abnormal synchronous oscillatory activity in animal models and patients. Yet, the possibility that variation in motor cortex activity drives transient overactivity in output nuclei neurons in parkinsonism has not been explored. In Sprague-Dawley rats with 6-hydroxydopamine (6-OHDA)-induced nigrostriatal lesions, approximately 50% substantia nigra pars reticulata (SNpr) units show abnormal cortically driven slow oscillations of discharge. Moreover, these units selectively show abnormal responses to motor cortex stimulation consisting in augmented excitations of an odd latency, which overlapped that of inhibitory responses presumptively mediated by the trans-striatal direct pathway in control rats. Delivering D1 or D2 dopamine agonists into the striatum of parkinsonian rats by reverse microdialysis reduced these abnormal excitations but had no effect on pathological oscillations. The present study establishes that dopamine-deficiency related changes of striatal function contribute to producing abnormally augmented excitatory responses to motor cortex stimulation in the SNpr. If a similar transient overactivity of basal ganglia output were driven by motor cortex input during movement, it could contribute to impeding movement initiation or execution in Parkinson's disease.

Experimental epidural hematoma causes cerebral infarction and activates neocortical glial and neuronal genesis in adult guinea pigs.

PubMed

Pan, Aihua; Li, Ming; Gao, Jun-Yan; Xue, Zhi-Qin; Li, Zhiyuan; Yuan, Xian-Yui; Luo, Duan-Wu; Luo, Xue-Gang; Yan, Xiao-Xin

2013-02-01

Epidural hematoma (EDH) is a type of life-threatening traumatic brain injury. Little is known about the extent to which EDH may cause neural damage and regenerative response in the cerebral cortex. Here we attempted to explore these issues by using guinea pigs as an experimental model. Unilateral EDH was induced by injection of 0.1 ml autologous blood into the extradural space, with experimental effects examined at 7, 14, 30, and 60 days postlesion. An infarct developed in the cortex deep to the EDH largely after 7 days postlesion, with neuronal death occurred from layers I to V in the central infarct region, as evidenced by loss of immunoreactivity (IR) for neuron-specific nuclear antigen (NeuN). Glial fibrillary acidic protein (GFAP) IR appeared as a cellular band surrounding the infarct and extending into the periinfarct cortex along the pia. Doublecortin (DCX) IR emerged in these same areas, with labeled cells appearing as astrocytic and neuronal profiles. DCX/GFAP colocalization was found in these regions commonly at 7 and 14 days postlesion, whereas DCX/NeuN-colabeled neurons were detectable at 30 and 60 days postlesion. Subpopulations of GFAP-, DCX-, or NeuN-immunoreactive cells colocalized with the endogenous proliferative marker Ki-67 or bromodeoxyuridine (BrdU) after pulse-chase with this birth-dating marker. The results suggest that experimental EDH can cause severe neuronal loss, induce significant glial activation, and promote a certain degree of local neuronal genesis in adult guinea pig neocortex. These findings point to potential therapeutic targets for improving neuronal recovery in clinical management of EDH. Copyright © 2012 Wiley Periodicals, Inc.

Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex.

PubMed

Lübke, Joachim; Feldmeyer, Dirk

2007-07-01

A basic feature of the neocortex is its organization in functional, vertically oriented columns, recurring modules of signal processing and a system of transcolumnar long-range horizontal connections. These columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical columns contain thousands of neurons and span all cortical layers. They receive input from other cortical areas and subcortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a cortical column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of cortical signal processing and the underlying neuronal 'microcircuits'. In the last decade the 'barrel' field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a cortical column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a cortical column, with emphasis on excitatory signal flow.

Selective Neuronal Activation by Cochlear Implant Stimulation in Auditory Cortex of Awake Primate

PubMed Central

Johnson, Luke A.; Della Santina, Charles C.

2016-01-01

Despite the success of cochlear implants (CIs) in human populations, most users perform poorly in noisy environments and music and tonal language perception. How CI devices engage the brain at the single neuron level has remained largely unknown, in particular in the primate brain. By comparing neuronal responses with acoustic and CI stimulation in marmoset monkeys unilaterally implanted with a CI electrode array, we discovered that CI stimulation was surprisingly ineffective at activating many neurons in auditory cortex, particularly in the hemisphere ipsilateral to the CI. Further analyses revealed that the CI-nonresponsive neurons were narrowly tuned to frequency and sound level when probed with acoustic stimuli; such neurons likely play a role in perceptual behaviors requiring fine frequency and level discrimination, tasks that CI users find especially challenging. These findings suggest potential deficits in central auditory processing of CI stimulation and provide important insights into factors responsible for poor CI user performance in a wide range of perceptual tasks. SIGNIFICANCE STATEMENT The cochlear implant (CI) is the most successful neural prosthetic device to date and has restored hearing in hundreds of thousands of deaf individuals worldwide. However, despite its huge successes, CI users still face many perceptual limitations, and the brain mechanisms involved in hearing through CI devices remain poorly understood. By directly comparing single-neuron responses to acoustic and CI stimulation in auditory cortex of awake marmoset monkeys, we discovered that neurons unresponsive to CI stimulation were sharply tuned to frequency and sound level. Our results point out a major deficit in central auditory processing of CI stimulation and provide important insights into mechanisms underlying the poor CI user performance in a wide range of perceptual tasks. PMID:27927962

Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex-Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB Receptors.

PubMed

Chang, Chun-Hui

2017-07-01

The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex and lateral orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal cortex activation exerts an inhibitory gating on medial prefrontal cortex-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to medial prefrontal cortex activation, tested lateral orbitofrontal cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined differential contribution of GABAA and GABAB receptors with iontophoresis. Relative to baseline, lateral orbitofrontal cortex stimulation exerted an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250, and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while blockade of GABAB receptors with saclofen reversed the inhibitory gating at long delay (100 milliseconds) only. Among the majority of the neurons examined (8 of 9), inactivation of either GABAA or GABAB receptors during baseline did not change evoked probability per se, suggesting that local feed-forward inhibitory mechanism is pathway specific. Our results suggest that the effect of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to 500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating on the medial prefrontal cortex-amygdala pathway. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Chromatic and Achromatic Spatial Resolution of Local Field Potentials in Awake Cortex

PubMed Central

Jansen, Michael; Li, Xiaobing; Lashgari, Reza; Kremkow, Jens; Bereshpolova, Yulia; Swadlow, Harvey A.; Zaidi, Qasim; Alonso, Jose-Manuel

2015-01-01

Local field potentials (LFPs) have become an important measure of neuronal population activity in the brain and could provide robust signals to guide the implant of visual cortical prosthesis in the future. However, it remains unclear whether LFPs can detect weak cortical responses (e.g., cortical responses to equiluminant color) and whether they have enough visual spatial resolution to distinguish different chromatic and achromatic stimulus patterns. By recording from awake behaving macaques in primary visual cortex, here we demonstrate that LFPs respond robustly to pure chromatic stimuli and exhibit ∼2.5 times lower spatial resolution for chromatic than achromatic stimulus patterns, a value that resembles the ratio of achromatic/chromatic resolution measured with psychophysical experiments in humans. We also show that, although the spatial resolution of LFP decays with visual eccentricity as is also the case for single neurons, LFPs have higher spatial resolution and show weaker response suppression to low spatial frequencies than spiking multiunit activity. These results indicate that LFP recordings are an excellent approach to measure spatial resolution from local populations of neurons in visual cortex including those responsive to color. PMID:25416722

Modulation of value representation by social context in the primate orbitofrontal cortex.

PubMed

Azzi, João C B; Sirigu, Angela; Duhamel, Jean-René

2012-02-07

Primates depend for their survival on their ability to understand their social environment, and their behavior is often shaped by social circumstances. We report that the orbitofrontal cortex, a brain region involved in motivation and reward, is tuned to social information. Macaque monkeys worked to collect rewards for themselves and two monkey partners. Behaviorally, monkeys discriminated between cues signaling large and small [corrected] rewards, and between cues signaling rewards to self only and reward to both self and another monkey, with a preference for the former over the latter in both instances. Single neurons recorded during this task encoded the meaning of visual cues that predicted the magnitude of future rewards, as well as the motivational value of rewards obtained in a social context. Furthermore, neuronal activity was found to track momentary social preferences and partner's identity and social rank. The orbitofrontal cortex thus contains key neuronal mechanisms for the evaluation of social information.

Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology.

PubMed

Schultz, Wolfram

2004-04-01

Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The involved brain structures include groups of dopamine neurons, the striatum including the nucleus accumbens, the orbitofrontal cortex and the amygdala. The reward information is fed to brain structures involved in decision-making and organisation of behaviour, such as the dorsolateral prefrontal cortex and possibly the parietal cortex. The neural coding of basic reward terms derived from formal theories puts the neurophysiological investigation of reward mechanisms on firm conceptual grounds and provides neural correlates for the function of rewards in learning, approach behaviour and decision-making.

Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuriya, Mutsuo; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582; Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa, 240-8501

Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This primingmore » effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. - Highlights: • Background NE augments the responsiveness of astrocytes to subsequent NE stimulation. • The priming effect is independent of neuronal activity and mediated by βadrenoceptor. • Background subthreshold NE may play gliomodulatory roles in the cerebral cortex.« less

Synaptic Plasticity Enables Adaptive Self-Tuning Critical Networks

PubMed Central

Stepp, Nigel; Plenz, Dietmar; Srinivasa, Narayan

2015-01-01

During rest, the mammalian cortex displays spontaneous neural activity. Spiking of single neurons during rest has been described as irregular and asynchronous. In contrast, recent in vivo and in vitro population measures of spontaneous activity, using the LFP, EEG, MEG or fMRI suggest that the default state of the cortex is critical, manifested by spontaneous, scale-invariant, cascades of activity known as neuronal avalanches. Criticality keeps a network poised for optimal information processing, but this view seems to be difficult to reconcile with apparently irregular single neuron spiking. Here, we simulate a 10,000 neuron, deterministic, plastic network of spiking neurons. We show that a combination of short- and long-term synaptic plasticity enables these networks to exhibit criticality in the face of intrinsic, i.e. self-sustained, asynchronous spiking. Brief external perturbations lead to adaptive, long-term modification of intrinsic network connectivity through long-term excitatory plasticity, whereas long-term inhibitory plasticity enables rapid self-tuning of the network back to a critical state. The critical state is characterized by a branching parameter oscillating around unity, a critical exponent close to -3/2 and a long tail distribution of a self-similarity parameter between 0.5 and 1. PMID:25590427

Discontinuous Patterns of Brain Activation in the Psychotherapy Process of Obsessive-Compulsive Disorder: Converging Results from Repeated fMRI and Daily Self-Reports

PubMed Central

Schiepek, Günter; Tominschek, Igor; Heinzel, Stephan; Aigner, Martin; Dold, Markus; Unger, Annemarie; Lenz, Gerhard; Windischberger, Christian; Moser, Ewald; Plöderl, Martin; Lutz, Jürgen; Meindl, Thomas; Zaudig, Michael; Pogarell, Oliver; Karch, Susanne

2013-01-01

This study investigates neuronal activation patterns during the psychotherapeutic process, assuming that change dynamics undergo critical instabilities and discontinuous transitions. An internet-based system was used to collect daily self-assessments during inpatient therapies. A dynamic complexity measure was applied to the resulting time series. Critical phases of the change process were indicated by the maxima of the varying complexity. Repeated functional magnetic resonance imaging (fMRI) measurements were conducted over the course of the therapy. The study was realized with 9 patients suffering from obsessive-compulsive disorder (subtype: washing/contamination fear) and 9 matched healthy controls. For symptom-provocative stimulation individualized pictures from patients’ personal environments were used. The neuronal responses to these disease-specific pictures were compared to the responses during standardized disgust-provoking and neutral pictures. Considerably larger neuronal changes in therapy-relevant brain areas (cingulate cortex/supplementary motor cortex, bilateral dorsolateral prefrontal cortex, bilateral insula, bilateral parietal cortex, cuneus) were observed during critical phases (order transitions), as compared to non-critical phases, and also compared to healthy controls. The data indicate that non-stationary changes play a crucial role in the psychotherapeutic process supporting self-organization and complexity models of therapeutic change. PMID:23977168

A Quantitative Analysis of Neurons with Kv3 Potassium Channel Subunits–Kv3.1b and Kv3.2–in Macaque Primary Visual Cortex

PubMed Central

Constantinople, Christine M.; Disney, Anita A; Maffie, Jonathan; Rudy, Bernardo; Hawken, Michael J

2010-01-01

Voltage-gated potassium channels that are composed of Kv3 subunits exhibit distinct electrophysiological properties: activation at more depolarized potentials than other voltage-gated K+ channels and fast kinetics. These channels have been shown to contribute to the high-frequency firing of fast-spiking (FS) GABAergic interneurons in the rat and mouse brain. In the rodent neocortex, there are distinct patterns of expression for the Kv3.1b and Kv3.2 channel subunits and of co-expression of these subunits with neurochemical markers, such as the calcium-binding proteins parvalbumin (PV) and calbindin D-28K (CB). The distribution of Kv3 channels and interrelationship with calcium-binding protein expression has not been investigated in primate cortex. We used immunoperoxidase and immunofluorescent labeling and stereological counting techniques to characterize the laminar and cell-type distributions of Kv3-ir neurons in macaque V1. We found that across the cortical layers ~25% of both Kv3.1b- and Kv3.2-ir neurons are non-GABAergic. In contrast all Kv3-ir neurons in rodent cortex are GABAergic (Chow et al., 1999). The putatively excitatory Kv3-ir neurons were mostly located in layers 2, 3 and 4b. Further, the proportion of Kv3-ir neurons that express PV or CB also differs between macaque V1 and rodent cortex. These data indicate that, within the population of cortical neurons, a broader population of neurons, encompassing cells of a wider range of morphological classes may be capable of sustaining high-frequency firing in macaque V1. PMID:19634181

Reduced expression of conditioned fear in the R6/2 mouse model of Huntington’s disease is related to abnormal activity in prelimbic cortex

PubMed Central

Walker, Adam G.; Ummel, Jason R.; Rebec, George V.

2011-01-01

Prefrontal cortex (PFC) dysfunction is common in patients with Huntington’s disease (HD), a dominantly inherited neurological disorder, and has been linked to cognitive disruption. We previously reported alterations in neuronal firing patterns recorded from PFC of the R6/2 mouse model of HD. To determine if PFC dysfunction results in behavioral impairments, we evaluated performance of wild-type (WT) and R6/2 mice in a fear conditioning and extinction behavioral task. Fear conditioning and extinction retrieval were similar in both genotypes, but R6/2s exhibited less fear during extinction by freezing less than WTs. A fear reinstatement test after extinction retrieval indicated that faster extinction was not due to poor memory for conditioning. During initial extinction and extinction retrieval training, neuronal activity was recorded from prelimbic (PL) cortex, a subregion of PFC known to be important for fear expression. In WTs, a large number of neurons were activated by the conditioned stimulus during initial extinction and this activation was significantly impaired in R6/2s. Notably, there was no genotype difference in PFC activity during extinction retrieval. Thus, altered extinction is likely a result of reduced fear expression due to impairments in PL activation. Collectively, our results suggest that PFC dysfunction may play a key role in R6/2 cognitive impairments. PMID:21515374

Ketamine-dependent neuronal activation in healthy volunteers.

PubMed

Höflich, Anna; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S; Vanicek, Thomas; Ganger, Sebastian; Spies, Marie; Windischberger, Christian; Kasper, Siegfried; Winkler, Dietmar; Lanzenberger, Rupert

2017-04-01

Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S ® ) was administered intravenously to 35 healthy volunteers. Neural activation as indicated by the BOLD signal using the pharmacokinetic curve of ketamine plasma levels as a regressor was computed. Compared with placebo, ketamine-dependent increases of neural activation were observed in the midcingulate cortex, the dorsal part of the anterior cingulate cortex, the insula bilaterally, and the thalamus (t values ranging between 5.95-9.78, p < 0.05; FWE-corrected). A significant decrease of neural activation in the ketamine condition compared to placebo was found in a cluster within the subgenual/subcallosal part of the anterior cingulate cortex, the orbitofrontal cortex and the gyrus rectus (t = 7.81, p < 0.05, FWE-corrected). Using an approach combining pharmacological and fMRI data, important information about the neurobiological correlates of the clinical antidepressant effects of ketamine could be revealed.

High Stimulus-Related Information in Barrel Cortex Inhibitory Interneurons

PubMed Central

Reyes-Puerta, Vicente; Kim, Suam; Sun, Jyh-Jang; Imbrosci, Barbara; Kilb, Werner; Luhmann, Heiko J.

2015-01-01

The manner in which populations of inhibitory (INH) and excitatory (EXC) neocortical neurons collectively encode stimulus-related information is a fundamental, yet still unresolved question. Here we address this question by simultaneously recording with large-scale multi-electrode arrays (of up to 128 channels) the activity of cell ensembles (of up to 74 neurons) distributed along all layers of 3–4 neighboring cortical columns in the anesthetized adult rat somatosensory barrel cortex in vivo. Using two different whisker stimulus modalities (location and frequency) we show that individual INH neurons – classified as such according to their distinct extracellular spike waveforms – discriminate better between restricted sets of stimuli (≤6 stimulus classes) than EXC neurons in granular and infra-granular layers. We also demonstrate that ensembles of INH cells jointly provide as much information about such stimuli as comparable ensembles containing the ~20% most informative EXC neurons, however presenting less information redundancy – a result which was consistent when applying both theoretical information measurements and linear discriminant analysis classifiers. These results suggest that a consortium of INH neurons dominates the information conveyed to the neocortical network, thereby efficiently processing incoming sensory activity. This conclusion extends our view on the role of the inhibitory system to orchestrate cortical activity. PMID:26098109

Transient enhancement of proliferation of neural progenitors and impairment of their long-term survival in p25 transgenic mice

PubMed Central

Dong, Fengping; Shu, Tianzhi; Zhou, Ying; Tsai, Li-Huei; Mao, Yingwei

2016-01-01

Cyclin-dependent kinase 5 (CDK5) regulates important neuronal functions via p35. p35 undergoes cleavage in response to neuronal activity and neurotoxic conditions to release its subunit p25. Although p25 has been implicated in various neurodegenerative diseases, the mechanisms by which p25 mediates neurodegenerative impairment have not been fully elucidated. We aimed to determine the role of p25-mediated neurodegeneration on neurogenesis in an inducible transgenic mouse line overexpressing p25 (p25 TG) in the forebrain. Adult neuronal progenitor cells (NPCs) were labeled with BrdU in vivo, which were significantly increased in numbers in the subventricular zone, the hippocampus, and the cortex of p25 TG mice. Consistently, more mitotic cells were observed in p25 TG mice than in controls, even in the cortex and the CA1, which are not neurogenic regions. BrdU-positive cells were negative for GFAP or γ-H2AX, suggesting that they are not astrocytes or dying cells. Neurospheres derived from the dentate gyrus and the cortex were significantly increased in p25 TG mice and can be differentiated into astrocytes and neurons. However, p25 TG decreased the long-term survival of proliferating NPCs and severely impaired adult neurogenesis. A Transwell co-culture system was used to assess the influence of p25-expressing primary neurons on adult NPCs. Co-culture with p25-expressing neurons downregulated Ki67 expression and upregulated cleaved caspase-3, indicating that the paracrine signaling in cell-cell communication is essential for NPC survival and proliferation. Moreover, increased CDK5 activity impairs Wnt activation. This study demonstrates that hyperactivation of p25 may temporarily enhance NPC proliferation, but impair their long-term survival. PMID:27283769

Transient enhancement of proliferation of neural progenitors and impairment of their long-term survival in p25 transgenic mice.

PubMed

Zou, Donghua; Zhou, Yijing; Liu, Long; Dong, Fengping; Shu, Tianzhi; Zhou, Ying; Tsai, Li-Huei; Mao, Yingwei

2016-06-28

Cyclin-dependent kinase 5 (CDK5) regulates important neuronal functions via p35. p35 undergoes cleavage in response to neuronal activity and neurotoxic conditions to release its subunit p25. Although p25 has been implicated in various neurodegenerative diseases, the mechanisms by which p25 mediates neurodegenerative impairment have not been fully elucidated. We aimed to determine the role of p25-mediated neurodegeneration on neurogenesis in an inducible transgenic mouse line overexpressing p25 (p25 TG) in the forebrain. Adult neuronal progenitor cells (NPCs) were labeled with BrdU in vivo, which were significantly increased in numbers in the subventricular zone, the hippocampus, and the cortex of p25 TG mice. Consistently, more mitotic cells were observed in p25 TG mice than in controls, even in the cortex and the CA1, which are not neurogenic regions. BrdU-positive cells were negative for GFAP or γ-H2AX, suggesting that they are not astrocytes or dying cells. Neurospheres derived from the dentate gyrus and the cortex were significantly increased in p25 TG mice and can be differentiated into astrocytes and neurons. However, p25 TG decreased the long-term survival of proliferating NPCs and severely impaired adult neurogenesis. A Transwell co-culture system was used to assess the influence of p25-expressing primary neurons on adult NPCs. Co-culture with p25-expressing neurons downregulated Ki67 expression and upregulated cleaved caspase-3, indicating that the paracrine signaling in cell-cell communication is essential for NPC survival and proliferation. Moreover, increased CDK5 activity impairs Wnt activation. This study demonstrates that hyperactivation of p25 may temporarily enhance NPC proliferation, but impair their long-term survival.

Orbitofrontal Cortical Neurons Encode Expectation-Driven Initiation of Reward-Seeking

PubMed Central

Aston-Jones, Gary

2014-01-01

Adaptive execution and inhibition of behavior are guided by the activity of neuronal populations across multiple frontal cortical areas. The rodent medial prefrontal cortex has been well studied with respect to these behaviors, influencing behavioral execution/inhibition based on context. Other frontal regions, in particular the orbitofrontal cortex (OFC), are critical in directing behavior to obtain rewards, but the relationship between OFC neuronal activity and response execution or inhibition has been poorly characterized. In particular, little is known about OFC with respect to extinction learning, an important example of context-guided response inhibition. Here, we recorded the activity of OFC neurons while rats performed a discriminative-stimulus (DS)-driven sucrose-seeking task followed by multiple days of extinction of the DS. OFC neuronal activity was maximally responsive (1) to reward-predicting stimuli (RS) that triggered a lever press (i.e., lever-response initiation) and (2) during reward-well approach in pursuit of sucrose (i.e., well-response initiation). RS presentation that was not followed by a lever press or RS presentation during extinction produced weak activation, as did nonrewarded stimulus (NS) presentation regardless of response (press or withhold) or session (DS-sucrose or extinction). Activity related to nonrewarded well entry was minor, and activity was significantly inhibited during reward consumption. Finally, OFC neuronal activity switched selectivity to track rewarded behaviors when the RS/NS contingencies were reversed. Thus, rather than signaling variables related to extinction or response inhibition, activity in OFC was strongest at the initiation of multiple components of reward-seeking behavior, most prominently when valid reward-predicting cues drove these behaviors. PMID:25080585

Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

PubMed

Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

2017-12-01

Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The Activation of the Mirror Neuron System during Action Observation and Action Execution with Mirror Visual Feedback in Stroke: A Systematic Review

PubMed Central

Zhang, Jack J. Q.; Welage, Nandana

2018-01-01

Objective To evaluate the concurrent and training effects of action observation (AO) and action execution with mirror visual feedback (MVF) on the activation of the mirror neuron system (MNS) and its relationship with the activation of the motor cortex in stroke individuals. Methods A literature search using CINAHL, PubMed, PsycINFO, Medline, Web of Science, and SCOPUS to find relevant studies was performed. Results A total of 19 articles were included. Two functional magnetic resonance imaging (fMRI) studies reported that MVF could activate the ipsilesional primary motor cortex as well as the MNS in stroke individuals, whereas two other fMRI studies found that the MNS was not activated by MVF in stroke individuals. Two clinical trials reported that long-term action execution with MVF induced a shift of activation toward the ipsilesional hemisphere. Five fMRI studies showed that AO activated the MNS, of which, three found the activation of movement-related areas. Five electroencephalography (EEG) studies demonstrated that AO or MVF enhanced mu suppression over the sensorimotor cortex. Conclusions MVF may contribute to stroke recovery by revising the interhemispheric imbalance caused by stroke due to the activation of the MNS. AO may also promote motor relearning in stroke individuals by activating the MNS and motor cortex. PMID:29853839

Role of Microglia Disturbances and Immune-Related Marker Abnormalities in Cortical Circuitry Dysfunction in Schizophrenia

PubMed Central

Volk, David W.

2017-01-01

Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia. PMID:28007586

Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and Global Excitatory" Inputs to the Basal Ganglia.

PubMed

Ozaki, Mitsunori; Sano, Hiromi; Sato, Shigeki; Ogura, Mitsuhiro; Mushiake, Hajime; Chiken, Satomi; Nakao, Naoyuki; Nambu, Atsushi

2017-12-01

To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information. © The Author 2017. Published by Oxford University Press.

A specific area of olfactory cortex involved in stress hormone responses to predator odours.

PubMed

Kondoh, Kunio; Lu, Zhonghua; Ye, Xiaolan; Olson, David P; Lowell, Bradford B; Buck, Linda B

2016-04-07

Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin-releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising <5% of the olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents.

Ultastructural analysis on acetylcholinesterase localization in the cerebellar cortex of teleosts.

PubMed

Contestabile, A; Villani, L; Ciani, F

1977-12-28

The histochemical localization of acetylcholinesterase (AChE) was studied by electron microscopy in the cerebellar cortex of the goldfish and the catfish. The patterns of enzyme distribution show noticeable differences in the two teleost species at the level of the corresponding cerebellar structures. Among the most distinctive features is the prevailing intracellular localization of enzyme activity in the goldfish and the prevailing extracellular localization in the catfish in the molecular layer and, to a lesser extent, the granular layer. Only quantitative differences in the ability to synthesize AChE can be recorded among the different cerebellar neurons in the two species, since all these neurons exhibit different amounts of enzyme activity linked to their cytoplasmic structures. Comparing the results obtained with those of previous histochemical, experimental and developmental researches, the hypothesis seems well founded that the embryonic pool of cerebellar neurons is made up of AChE-synthesizing nruroblasts which, during development, loss or maintain to a different the mechanisms for AChE synthesis. In addition the light and electron microscope histochemistry reveals at different levels of resolution that the final pattern of AChE distribution in the cerebellar cortex is the sum of different degress of AChE synthesis by cerebellar neurons and different degrees of enzyme release in extracellular spaces.

Inactivation of the Prelimbic Cortex Impairs the Context-Induced Reinstatement of Ethanol Seeking.

PubMed

Palombo, Paola; Leao, Rodrigo M; Bianchi, Paula C; de Oliveira, Paulo E C; Planeta, Cleopatra da Silva; Cruz, Fábio C

2017-01-01

Evidence indicates that drug relapse in humans is often provoked by exposure to the self-administered drug-associated context. An animal model called "ABA renewal procedure" has been used to study the context-induced relapse to drug seeking. Here, we reported a new and feasible training procedure for the ABA renewal method to explore the role of the prelimbic cortex in context-induced relapse to ethanol seeking. By using a saccharin fading technique, we trained rats to self-administer ethanol (10%). The drug delivery was paired with a discrete tone-light cue. Lever pressing was subsequently extinguished in a non-drug-associated context in the presence of the discrete cue. Rats were subsequently tested for reinstatement in contexts A or B, under extinction conditions. Ethanol-associated context induced the reinstatement of ethanol seeking and increased the expression of Fos in the prelimbic cortex. The rate of neural activation in the prelimbic cortex was 3.4% in the extinction context B and 7.7% in the drug-associated context A, as evidenced by double-labeling of Fos and the neuron-specific protein NeuN. The reversible inactivation of the neural activity in the prelimbic cortex with gamma-Aminobutyric acid (GABA) receptor agonists (muscimol + baclofen) attenuated the context-induced reinstatement of ethanol self-administration. These results demonstrated that the neuronal activation of the prelimbic cortex is involved in the context-induced reinstatement of ethanol seeking.

Neural Representations of Personally Familiar and Unfamiliar Faces in the Anterior Inferior Temporal Cortex of Monkeys

PubMed Central

Eifuku, Satoshi; De Souza, Wania C.; Nakata, Ryuzaburo; Ono, Taketoshi; Tamura, Ryoi

2011-01-01

To investigate the neural representations of faces in primates, particularly in relation to their personal familiarity or unfamiliarity, neuronal activities were chronically recorded from the ventral portion of the anterior inferior temporal cortex (AITv) of macaque monkeys during the performance of a facial identification task using either personally familiar or unfamiliar faces as stimuli. By calculating the correlation coefficients between neuronal responses to the faces for all possible pairs of faces given in the task and then using the coefficients as neuronal population-based similarity measures between the faces in pairs, we analyzed the similarity/dissimilarity relationship between the faces, which were potentially represented by the activities of a population of the face-responsive neurons recorded in the area AITv. The results showed that, for personally familiar faces, different identities were represented by different patterns of activities of the population of AITv neurons irrespective of the view (e.g., front, 90° left, etc.), while different views were not represented independently of their facial identities, which was consistent with our previous report. In the case of personally unfamiliar faces, the faces possessing different identities but presented in the same frontal view were represented as similar, which contrasts with the results for personally familiar faces. These results, taken together, outline the neuronal representations of personally familiar and unfamiliar faces in the AITv neuronal population. PMID:21526206

The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding

PubMed Central

Ribeiro, Pedro F. M.; Ventura-Antunes, Lissa; Gabi, Mariana; Mota, Bruno; Grinberg, Lea T.; Farfel, José M.; Ferretti-Rebustini, Renata E. L.; Leite, Renata E. P.; Filho, Wilson J.; Herculano-Houzel, Suzana

2013-01-01

The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas. PMID:24032005

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex.

PubMed

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-07-06

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features.

Depression of neuronal excitability and epileptic activities by group II metabotropic glutamate receptors in the medial entorhinal cortex.

PubMed

Zhang, Haopeng; Cilz, Nicholas I; Yang, Chuanxiu; Hu, Binqi; Dong, Hailong; Lei, Saobo

2015-11-01

Whereas the ionotropic glutamate receptors are the major mediator in glutamatergic transmission, the metabotropic glutamate receptors (mGluRs) usually play a modulatory role. Whereas the entorhinal cortex (EC) is an essential structure involved in the generation and propagation of epilepsy, the roles and mechanisms of mGluRs in epilepsy in the EC have not been determined. Here, we studied the effects of activation of group II metabotropic glutamate receptors (mGluRs II) on epileptiform activity induced by picrotoxin or deprivation of extracellular Mg2+ and neuronal excitability in the medial EC. We found that activation of mGluRs II by application of the selective agonist, LY354740, exerted robust inhibition on epileptiform activity. LY354740 hyperpolarized entorhinal neurons via activation of a K+ conductance and inhibition of a Na+ -permeable channel. LY354740-induced hyperpolarization was G protein-dependent, but independent of adenylyl cyclase and protein kinase A. However, the function of Gβγ was involved in mGluRs II-mediated depression of both neuronal excitability and epileptiform activity. Our results provide a novel cellular mechanism to explain the antiepileptic effects of mGluRs II in the treatment of epilepsy. © 2015 Wiley Periodicals, Inc.

Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris).

PubMed

Reyes, Laura D; Harland, Tessa; Reep, Roger L; Sherwood, Chet C; Jacobs, Bob

2016-01-01

The current study investigates neuron morphology in presumptive primary somatosensory (S1) and primary visual (V1) cortices of the Florida manatee (Trichechus manatus latirostris) as revealed by Golgi impregnation. Sirenians, including manatees, have an aquatic lifestyle, a large body size, and a relatively large lissencephalic brain. The present study examines neuron morphology in 3 cortical areas: in S1, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2) and in V1, dorsolateral cortex area 4 (DL4). Neurons exhibited a variety of morphological types, with pyramidal neurons being the most common. The large variety of neuron types present in the manatee cortex was comparable to that seen in other eutherian mammals, except for rodents and primates, where pyramid-shaped neurons predominate. A comparison between pyramidal neurons in S1 and V1 indicated relatively greater dendritic branching in S1. Across all 3 areas, the dendritic arborization pattern of pyramidal neurons was also similar to that observed previously in the afrotherian rock hyrax, cetartiodactyls, opossums, and echidnas but did not resemble the widely bifurcated dendrites seen in the large-brained African elephant. Despite adaptations for an aquatic environment, manatees did not share specific neuron types such as tritufted and star-like neurons that have been found in cetaceans. Manatees exhibit an evolutionarily primitive pattern of cortical neuron morphology shared with most other mammals and do not appear to have neuronal specializations for an aquatic niche. © 2016 S. Karger AG, Basel.

Homeostatic circuits selectively gate food cue responses in insular cortex

PubMed Central

Livneh, Yoav; Ramesh, Rohan n.; Burgess, christian R.; Levandowski, Kirsten M.; Madara, Joseph c.; Fenselau, henning; Goldey, Glenn J.; Diaz, Veronica E.; Jikomes, nick; Resch, Jon M.; Lowell, Bradford B.; Andermann, Mark L.

2017-01-01

Physiological needs bias perception and attention to relevant sensory cues. This process is ‘hijacked’ by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how ‘cognitive’ cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food- cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic ‘hunger neurons’ (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues. PMID:28614299

Dynamic encoding of responses and outcomes by neurons in medial prefrontal cortex

PubMed Central

Luk, Chung-Hay; Wallis, Jonathan D.

2009-01-01

Medial prefrontal cortex (MPFC) and lateral prefrontal cortex (LPFC) both contribute to goal-directed behavior, but their precise role remains unclear. Several lines of evidence suggest that MPFC is more important than LPFC for outcome-guided response selection. To examine this, we trained two subjects to perform a task that required them to monitor the specific outcome associated with a specific response on a trial-by-trial basis. While the subjects performed this task, we recorded the electrical activity of single neurons simultaneously from MPFC and LPFC. There were marked differences in the neuronal properties of these two areas. Neurons encoding the response were present in both areas, but in MPFC, there were also neurons that encoded the outcome. In particular, neurons encoded the subject’s intended response and how preferable the received outcome was. Thus, only in MPFC was all the information necessary to solve the task encoded. In addition, largely separate populations of MPFC neurons encoded the response and the outcome. Neurons encoding the outcome were in the anterior parts of MPFC: posterior to the corpus callosum there was a marked drop in their incidence. Our results suggest differences in the contribution of MPFC and LPFC to action control. MPFC neurons encode the desirability of the outcome produced by a specific response on a trial-by-trial basis. This capability may contribute to several of the functions of MPFC, such as action valuation, error detection and decision-making. PMID:19515921

Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex.

PubMed

Higo, Noriyuki; Kunori, Nobuo; Murata, Yumi

2016-01-01

In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 μA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 μA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv.

Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex

PubMed Central

Kunori, Nobuo; Murata, Yumi

2016-01-01

In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 μA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 μA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv. PMID:27494282

Equalization of Synaptic Efficacy by Synchronous Neural Activity

NASA Astrophysics Data System (ADS)

Cho, Myoung Won; Choi, M. Y.

2007-11-01

It is commonly believed that spike timings of a postsynaptic neuron tend to follow those of the presynaptic neuron. Such orthodromic firing may, however, cause a conflict with the functional integrity of complex neuronal networks due to asymmetric temporal Hebbian plasticity. We argue that reversed spike timing in a synapse is a typical phenomenon in the cortex, which has a stabilizing effect on the neuronal network structure. We further demonstrate how the firing causality in a synapse is perturbed by synchronous neural activity and how the equilibrium property of spike-timing dependent plasticity is determined principally by the degree of synchronization. Remarkably, even noise-induced activity and synchrony of neurons can result in equalization of synaptic efficacy.

Mapping the spatio-temporal structure of motor cortical LFP and spiking activities during reach-to-grasp movements

PubMed Central

Riehle, Alexa; Wirtssohn, Sarah; Grün, Sonja; Brochier, Thomas

2013-01-01

Grasping an object involves shaping the hand and fingers in relation to the object’s physical properties. Following object contact, it also requires a fine adjustment of grasp forces for secure manipulation. Earlier studies suggest that the control of hand shaping and grasp force involve partially segregated motor cortical networks. However, it is still unclear how information originating from these networks is processed and integrated. We addressed this issue by analyzing massively parallel signals from population measures (local field potentials, LFPs) and single neuron spiking activities recorded simultaneously during a delayed reach-to-grasp task, by using a 100-electrode array chronically implanted in monkey motor cortex. Motor cortical LFPs exhibit a large multi-component movement-related potential (MRP) around movement onset. Here, we show that the peak amplitude of each MRP component and its latency with respect to movement onset vary along the cortical surface covered by the array. Using a comparative mapping approach, we suggest that the spatio-temporal structure of the MRP reflects the complex physical properties of the reach-to-grasp movement. In addition, we explored how the spatio-temporal structure of the MRP relates to two other measures of neuronal activity: the temporal profile of single neuron spiking activity at each electrode site and the somatosensory receptive field properties of single neuron activities. We observe that the spatial representations of LFP and spiking activities overlap extensively and relate to the spatial distribution of proximal and distal representations of the upper limb. Altogether, these data show that, in motor cortex, a precise spatio-temporal pattern of activation is involved for the control of reach-to-grasp movements and provide some new insight about the functional organization of motor cortex during reaching and object manipulation. PMID:23543888

Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

PubMed Central

Allen, William E.; Kauvar, Isaac V.; Chen, Michael Z.; Richman, Ethan B.; Yang, Samuel J.; Chan, Ken; Gradinaru, Viviana; Deverman, Benjamin E.; Luo, Liqun; Deisseroth, Karl

2017-01-01

SUMMARY The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information. PMID:28521139

Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

PubMed Central

Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.; Kuo, Chay T.; Wadiche, Jacques I.; Overstreet-Wadiche, Linda

2016-01-01

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spike due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations. PMID:27095423

Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spikemore » due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Here, our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.« less

Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

DOE PAGES

Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.; ...

2016-04-20

Persistent neurogenesis in the dentate gyrus produces immature neurons with high intrinsic excitability and low levels of inhibition that are predicted to be more broadly responsive to afferent activity than mature neurons. Mounting evidence suggests that these immature neurons are necessary for generating distinct neural representations of similar contexts, but it is unclear how broadly responsive neurons help distinguish between similar patterns of afferent activity. Here we show that stimulation of the entorhinal cortex in mouse brain slices paradoxically generates spiking of mature neurons in the absence of immature neuron spiking. Immature neurons with high intrinsic excitability fail to spikemore » due to insufficient excitatory drive that results from low innervation rather than silent synapses or low release probability. Here, our results suggest that low synaptic connectivity prevents immature neurons from responding broadly to cortical activity, potentially enabling excitable immature neurons to contribute to sparse and orthogonal dentate representations.« less

Polarity of cortical electrical stimulation differentially affects neuronal activity of deep and superficial layers of rat motor cortex.

PubMed

Yazdan-Shahmorad, Azadeh; Kipke, Daryl R; Lehmkuhle, Mark J

2011-10-01

Cortical electrical stimulation (CES) techniques are practical tools in neurorehabilitation that are currently being used to test models of functional recovery after neurologic injury. However, the mechanisms by which CES has therapeutic effects, are not fully understood. In this study, we investigated the effects of CES on unit activity of different neuronal elements in layers of rat primary motor cortex after the offset of stimulation. We evaluated the effects of monopolar CES pulse polarity (anodic-first versus cathodic-first) using various stimulation frequencies and amplitudes on unit activity after stimulation. A penetrating single shank silicon microelectrode array enabled us to span the entirety of six layer motor cortex allowing simultaneous electrophysiologic recordings from different depths after monopolar CES. Neural spiking activity before the onset and after the offset of CES was modeled using point processes fit to capture neural spiking dynamics as a function of extrinsic stimuli based on generalized linear model methods. We found that neurons in lower layers have a higher probability of being excited after anodic CES. Conversely, neurons located in upper cortical layers have a higher probability of being excited after cathodic stimulation. The opposing effects observed following anodic versus cathodic stimulation in upper and lower layers were frequency- and amplitude-dependent. The data demonstrates that the poststimulus changes in neural activity after manipulation of CES parameters changes according to the location (depth) of the recorded units in rat primary motor cortex. The most effective pulse polarity for eliciting action potentials after stimulation in lower layers was not as effective in upper layers. Likewise, lower amplitudes and frequencies of CES were more effective than higher amplitudes and frequencies for eliciting action potentials. These results have important implications in the context of maximizing efficacy of CES for neurorehabilitation and neuroprosthetic applications. Copyright © 2011 Elsevier Inc. All rights reserved.

Basal ganglia—thalamus and the “crowning enigma”

PubMed Central

Garcia-Munoz, Marianela; Arbuthnott, Gordon W.

2015-01-01

When Hubel (1982) referred to layer 1 of primary visual cortex as “… a ‘crowning mystery’ to keep area-17 physiologists busy for years to come …” he could have been talking about any cortical area. In the 80’s and 90’s there were no methods to examine this neuropile on the surface of the cortex: a tangled web of axons and dendrites from a variety of different places with unknown specificities and doubtful connections to the cortical output neurons some hundreds of microns below. Recently, three changes have made the crowning enigma less of an impossible mission: the clear presence of neurons in layer 1 (L1), the active conduction of voltage along apical dendrites and optogenetic methods that might allow us to look at one source of input at a time. For all of those reasons alone, it seems it is time to take seriously the function of L1. The functional properties of this layer will need to wait for more experiments but already L1 cells are GAD67 positive, i.e., inhibitory! They could reverse the sign of the thalamic glutamate (GLU) input for the entire cortex. It is at least possible that in the near future normal activity of individual sources of L1 could be detected using genetic tools. We are at the outset of important times in the exploration of thalamic functions and perhaps the solution to the crowning enigma is within sight. Our review looks forward to that solution from the solid basis of the anatomy of the basal ganglia output to motor thalamus. We will focus on L1, its afferents, intrinsic neurons and its influence on responses of pyramidal neurons in layers 2/3 and 5. Since L1 is present in the whole cortex we will provide a general overview considering evidence mainly from the somatosensory (S1) cortex before focusing on motor cortex. PMID:26582979

Mechanisms of inhibition in cat visual cortex.

PubMed Central

Berman, N J; Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Neurones from layers 2-6 of the cat primary visual cortex were studied using extracellular and intracellular recordings made in vivo. The aim was to identify inhibitory events and determine whether they were associated with small or large (shunting) changes in the input conductance of the neurones. 2. Visual stimulation of subfields of simple receptive fields produced depolarizing or hyperpolarizing potentials that were associated with increased or decreased firing rates respectively. Hyperpolarizing potentials were small, 5 mV or less. In the same neurones, brief electrical stimulation of cortical afferents produced a characteristic sequence of a brief depolarization followed by a long-lasting (200-400 ms) hyperpolarization. 3. During the response to a stationary flashed bar, the synaptic activation increased the input conductance of the neurone by about 5-20%. Conductance changes of similar magnitude were obtained by electrically stimulating the neurone. Neurones stimulated with non-optimal orientations or directions of motion showed little change in input conductance. 4. These data indicate that while visually or electrically induced inhibition can be readily demonstrated in visual cortex, the inhibition is not associated with large sustained conductance changes. Thus a shunting or multiplicative inhibitory mechanism is not the principal mechanism of inhibition. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1804983

Balanced feedforward inhibition and dominant recurrent inhibition in olfactory cortex

PubMed Central

Large, Adam M.; Vogler, Nathan W.; Mielo, Samantha; Oswald, Anne-Marie M.

2016-01-01

Throughout the brain, the recruitment of feedforward and recurrent inhibition shapes neural responses. However, disentangling the relative contributions of these often-overlapping cortical circuits is challenging. The piriform cortex provides an ideal system to address this issue because the interneurons responsible for feedforward and recurrent inhibition are anatomically segregated in layer (L) 1 and L2/3 respectively. Here we use a combination of optical and electrical activation of interneurons to profile the inhibitory input received by three classes of principal excitatory neuron in the anterior piriform cortex. In all classes, we find that L1 interneurons provide weaker inhibition than L2/3 interneurons. Nonetheless, feedforward inhibitory strength covaries with the amount of afferent excitation received by each class of principal neuron. In contrast, intracortical stimulation of L2/3 evokes strong inhibition that dominates recurrent excitation in all classes. Finally, we find that the relative contributions of feedforward and recurrent pathways differ between principal neuron classes. Specifically, L2 neurons receive more reliable afferent drive and less overall inhibition than L3 neurons. Alternatively, L3 neurons receive substantially more intracortical inhibition. These three features—balanced afferent drive, dominant recurrent inhibition, and differential recruitment by afferent vs. intracortical circuits, dependent on cell class—suggest mechanisms for olfactory processing that may extend to other sensory cortices. PMID:26858458

The mammalian neocortex new pyramidal neuron: a new conception.

PubMed

Marín-Padilla, Miguel

2014-01-06

The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex subplate zone). From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating its developing motor activities. The new pyramidal neuron' distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface) without losing its original attachment to first layer or the location of its soma and, hence, retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs two pyramidal cell functional strata to carry out all its motor activities, the mouse 3, cat 4, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing and thinking as a premotor activity. Words used in language are the motor expression of thoughts and represent sounds produced by maneuvering the column of expiratory air by coordinated motor quivering as it passes through the larynx, pharynx, mouth, tongue, and lips. Homo sapiens cerebrum has developed new motor centers to communicate mental thoughts (and/or intention) through motor actions.

Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

PubMed

Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho

2012-12-06

Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

Annual life-history dependent seasonal differences in neural activity of the olfactory system between non-migratory and migratory songbirds.

PubMed

Rastogi, Ashutosh; Surbhi; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

2016-01-01

Present study investigated seasonal plasticity in neural activity of the olfactory system, and assessed whether this was influenced by differences in seasonal life-history states (LHSs) between the non-migratory and migratory birds. Brains of non-migratory Indian weaver birds and migratory redheaded buntings were processed for ZENK immunohistochemistry, a marker of neuronal activation, at the times of equinoxes (March, September) and solstices (June, December), which correspond with the periods of different seasonal LHSs during the year. Immunoreactivity was quantified in brain regions comprising the olfactory system viz. olfactory bulb (OB), anterior olfactory nucleus (AON), prepiriform cortex (CPP), lateral olfactory tract (LOT) and olfactory cortex (piriform cortex, CPI; lateral olfactory cortex, LOC). In weaver birds, ZENK-like immunoreactive (ZENK-lir) cells were significantly higher in all the brain areas during post-breeding season (September) than during the other seasons; OBs had higher neuronal activity in the breeding season (June), however. A similar neural activity pattern but at enhanced levels was found in migratory buntings almost all the year. These results for the first time show LHS-associated differences in the seasonal plasticity of a sensory system between the non-migratory and migratory songbirds. Copyright © 2015 Elsevier B.V. All rights reserved.

Serotonin Modulation of Prefronto-Hippocampal Rhythms in Health and Disease.

PubMed

Puig, M Victoria; Gener, Thomas

2015-07-15

There is mounting evidence that most cognitive functions depend upon the coordinated activity of neuronal networks often located far from each other in the brain. Ensembles of neurons synchronize their activity, generating oscillations at different frequencies that may encode behavior by allowing an efficient communication between brain areas. The serotonin system, by virtue of the widespread arborisation of serotonergic neurons, is in an excellent position to exert strong modulatory actions on brain rhythms. These include specific oscillatory activities in the prefrontal cortex and the hippocampus, two brain areas essential for many higher-order cognitive functions. Psychiatric patients show abnormal oscillatory activities in these areas, notably patients with schizophrenia who display psychotic symptoms as well as affective and cognitive impairments. Synchronization of neural activity between the prefrontal cortex and the hippocampus seems to be important for cognition and, in fact, reduced prefronto-hippocampal synchrony has been observed in a genetic mouse model of schizophrenia. Here, we review recent advances in the field of neuromodulation of brain rhythms by serotonin, focusing on the actions of serotonin in the prefrontal cortex and the hippocampus. Considering that the serotonergic system plays a crucial role in cognition and mood and is a target of many psychiatric treatments, it is surprising that this field of research is still in its infancy. In that regard, we point to future investigations that are much needed in this field.

Functional versus effector-specific organization of the human posterior parietal cortex: revisited

PubMed Central

Leone, Frank T. M.; Medendorp, W. Pieter

2016-01-01

It has been proposed that the posterior parietal cortex (PPC) is characterized by an effector-specific organization. However, strikingly similar functional MRI (fMRI) activation patterns have been found in the PPC for hand and foot movements. Because the fMRI signal is related to average neuronal activity, similar activation levels may result either from effector-unspecific neurons or from intermingled subsets of effector-specific neurons within a voxel. We distinguished between these possibilities using fMRI repetition suppression (RS). Participants made delayed, goal-directed eye, hand, and foot movements to visual targets. In each trial, the instructed effector was identical or different to that of the previous trial. RS effects indicated an attenuation of the fMRI signal in repeat trials. The caudal PPC was active during the delay but did not show RS, suggesting that its planning activity was effector independent. Hand and foot-specific RS effects were evident in the anterior superior parietal lobule (SPL), extending to the premotor cortex, with limb overlap in the anterior SPL. Connectivity analysis suggested information flow between the caudal PPC to limb-specific anterior SPL regions and between the limb-unspecific anterior SPL toward limb-specific motor regions. These results underline that both function and effector specificity should be integrated into a concept of PPC action representation not only on a regional but also on a fine-grained, subvoxel level. PMID:27466132

Population activity structure of excitatory and inhibitory neurons

PubMed Central

Doiron, Brent

2017-01-01

Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure. PMID:28817581

Independent Neuronal Representation of Facial and Vocal Identity in the Monkey Hippocampus and Inferotemporal Cortex.

PubMed

Sliwa, Julia; Planté, Aurélie; Duhamel, Jean-René; Wirth, Sylvia

2016-03-01

Social interactions make up to a large extent the prime material of episodic memories. We therefore asked how social signals are coded by neurons in the hippocampus. Human hippocampus is home to neurons representing familiar individuals in an abstract and invariant manner ( Quian Quiroga et al. 2009). In contradistinction, activity of rat hippocampal cells is only weakly altered by the presence of other rats ( von Heimendahl et al. 2012; Zynyuk et al. 2012). We probed the activity of monkey hippocampal neurons to faces and voices of familiar and unfamiliar individuals (monkeys and humans). Thirty-one percent of neurons recorded without prescreening responded to faces or to voices. Yet responses to faces were more informative about individuals than responses to voices and neuronal responses to facial and vocal identities were not correlated, indicating that in our sample identity information was not conveyed in an invariant manner like in human neurons. Overall, responses displayed by monkey hippocampal neurons were similar to the ones of neurons recorded simultaneously in inferotemporal cortex, whose role in face perception is established. These results demonstrate that the monkey hippocampus participates in the read-out of social information contrary to the rat hippocampus, but possibly lack an explicit conceptual coding of as found in humans. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

PubMed Central

Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

2016-01-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

Gender differences in human single neuron responses to male emotional faces.

PubMed

Newhoff, Morgan; Treiman, David M; Smith, Kris A; Steinmetz, Peter N

2015-01-01

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p < 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala.

Nicotine modulates multiple regions in the limbic stress network regulating activation of hypophysiotrophic neurons in hypothalamic paraventricular nucleus.

PubMed

Yu, Guoliang; Sharp, Burt M

2012-08-01

Nicotine intake affects CNS responses to stressors. We reported that nicotine self-administration (SA) augmented the hypothalamo-pituitary-adrenal (HPA) stress response, in part because of the altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic-PVN interactions involving medial prefrontal cortex, amygdala, and bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress-induced neuronal activation in limbic-PVN network, using c-Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress-induced c-Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri-PVN, but increased c-Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro-gold (FG) was injected into avBST or PVN, as GABAergic neurons in avBST projecting to PVN corticotrophin-releasing factor neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress-induced c-Fos expression in retrograde-labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic-PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic-BST-PVN interactions underlying the disinhibition of PVN corticotrophin-releasing factor neurons, an essential component of the amplified HPA response to stress by nicotine. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Pharmacological modulation of the voltage-gated neuronal Kv7/KCNQ/M-channel alters the intrinsic excitability and synaptic responses of pyramidal neurons in rat prefrontal cortex slices.

PubMed

Peng, Hui; Bian, Xi-Ling; Ma, Fu-Cui; Wang, Ke-Wei

2017-09-01

The prefrontal cortex (PFC) critical for higher cognition is implicated in neuropsychiatric diseases, such as Alzheimer's disease, depression and schizophrenia. The voltage-activated Kv7/KCNQ/M-channel or M-current modulates the neuronal excitability that defines the fundamental mechanism of brain function. However, whether M-current functions to regulate the excitability of PFC neurons remains elusive. In this study, we recorded the native M-current from PFC layer V pyramidal neurons in rat brain slices and showed that it modulated the intrinsic excitability and synaptic responses of PFC pyramidal neurons. Application of a specific M-channel blocker XE991 (40 μmol/L) or opener retigabine (10 μmol/L) resulted in inhibition or activation of M-current, respectively. In the current-clamp recordings, inhibition of M-current was evidenced by the increased average spike frequency and the reduced first inter-spike interval (ISI), spike onset latency and fast afterhyperpolarization (fAHP), whereas activation of M-current caused opposite responses. Furthermore, inhibition of M-current significantly increased the amplitude of excitatory postsynaptic potentials (EPSPs) and depolarized the resting membrane potential (RMP) without affecting the miniature EPSC (mEPSC) frequency. These data demonstrate that voltage-gated neuronal Kv7/KCNQ/M-current modulates the excitability and synaptic transmission of PFC neurons, suggesting that pharmacological modulation of M-current in the PFC may exert beneficial effects on cognitive deficits implicated in the pathophysiology of neuropsychiatric disorders.

Ketamine-induced apoptosis in the mouse cerebral cortex follows similar characteristic of physiological apoptosis and can be regulated by neuronal activity.

PubMed

Wang, Qi; Shen, Feng-Yan; Zou, Rong; Zheng, Jing-Jing; Yu, Xiang; Wang, Ying-Wei

2017-06-17

The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry. To explore the effect of neural activity on ketamine-induced apoptosis, the approaches of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and an environmental enrichment (EE) were performed. Ketamine-induced apoptosis in S1 is most prominent at postnatal days 5 and 7 (P5 - P7), and becomes insignificant by P12. Physiological and ketamine-induced apoptosis follow similar developmental patterns, mostly comprised of layer V pyramidal neurons at P5 and shifting to mostly layer II to IV GABAergic neurons by P9. Changes in neuronal activity induced by the DREADD system bidirectionally regulated the pattern of ketamine-induced apoptosis, with reduced activity inducing increased apoptosis and shifting the lamination pattern to a more immature form. Importantly, rearing mice in an EE significantly reduced the magnitude of ketamine-induced apoptosis and shifted its developmental pattern to a more mature form. Together, these results demonstrate that lamination pattern and cell-type dependent vulnerability to ketamine-induced apoptosis follow the physiological apoptosis pattern and are age- and activity-dependent. Naturally elevating neuronal activity is a possible method for reducing the adverse effects of general anesthesia.

Noradrenaline and acetylcholine responsiveness of glucose-monitoring and glucose-insensitive neurons in the mediodorsal prefrontal cortex.

PubMed

Nagy, Bernadett; Szabó, István; Csetényi, Bettina; Hormay, Edina; Papp, Szilárd; Keresztes, Dóra; Karádi, Zoltán

2014-01-16

The mediodorsal prefrontal cortex (mdPFC), as part of the forebrain glucose-monitoring (GM) system, plays important role in several regulatory processes to control the internal state of the organism and to initiate behavioral outputs accordingly. Little is known, however, about the neurochemical sensitivity of neurons located in this area. Substantial evidence indicates that the locus ceruleus - noradrenaline (NA) projection system and the nucleus basalis magnocellularis - cholinergic projection system regulate behavioral state and state dependent processing of sensory information, various cognitive functions already associated with the mdPFC. The main goal of the present study was to examine noradrenergic and cholinergic responsiveness of glucose-monitoring and glucose-insensitive (GIS) neurons in the mediodorsal prefrontal cortex. One fifth of the neurons tested changed in firing rate to microelectrophoretically applied NA. Responsiveness of the GM cells to this catecholamine proved to be significantly higher than that of the GIS units. Microiontophoretic application of acetylcholine (Ach) resulted in activity changes (predominantly facilitation) of more than 40% of the mdPFC neurons. Proportion of Ach sensitive units among the GM and the GIS neurons was found to be similar. The glucose-monitoring neurons of the mdPFC and their distinct NA and remarkable Ach sensitivity are suggested to be of particular significance in prefrontal control of adaptive behaviors. © 2013 Published by Elsevier B.V.

Natural asynchronies in audiovisual communication signals regulate neuronal multisensory interactions in voice-sensitive cortex.

PubMed

Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K; Petkov, Christopher I

2015-01-06

When social animals communicate, the onset of informative content in one modality varies considerably relative to the other, such as when visual orofacial movements precede a vocalization. These naturally occurring asynchronies do not disrupt intelligibility or perceptual coherence. However, they occur on time scales where they likely affect integrative neuronal activity in ways that have remained unclear, especially for hierarchically downstream regions in which neurons exhibit temporally imprecise but highly selective responses to communication signals. To address this, we exploited naturally occurring face- and voice-onset asynchronies in primate vocalizations. Using these as stimuli we recorded cortical oscillations and neuronal spiking responses from functional MRI (fMRI)-localized voice-sensitive cortex in the anterior temporal lobe of macaques. We show that the onset of the visual face stimulus resets the phase of low-frequency oscillations, and that the face-voice asynchrony affects the prominence of two key types of neuronal multisensory responses: enhancement or suppression. Our findings show a three-way association between temporal delays in audiovisual communication signals, phase-resetting of ongoing oscillations, and the sign of multisensory responses. The results reveal how natural onset asynchronies in cross-sensory inputs regulate network oscillations and neuronal excitability in the voice-sensitive cortex of macaques, a suggested animal model for human voice areas. These findings also advance predictions on the impact of multisensory input on neuronal processes in face areas and other brain regions.

Static and dynamic views of visual cortical organization.

PubMed

Casagrande, Vivien A; Xu, Xiangmin; Sáry, Gyula

2002-01-01

Without the aid of modern techniques Cajal speculated that cells in the visual cortex were connected in circuits. From Cajal's time until fairly recently, the flow of information within the cells and circuits of visual cortex has been described as progressing from input to output, from sensation to action. In this chapter we argue that a paradigm shift in our concept of the visual cortical neuron is under way. The most important change in our view concerns the neuron's functional role. Visual cortical neurons do not have static functional signatures but instead function dynamically depending on the ongoing activity of the networks to which they belong. These networks are not merely top-down or bottom-up unidirectional transmission lines, but rather represent machinery that uses recurrent information and is dynamic and highly adaptable. With the advancement of technology for analyzing the conversations of multiple neurons at many levels in the visual system and higher resolution imaging, we predict that the paradigm shift will progress to the point where neurons are no longer viewed as independent processing units but as members of subsets of networks where their role is mapped in space-time coordinates in relationship to the other neuronal members. This view moves us far from Cajal's original views of the neuron. Nevertheless, we believe that understanding the basic morphology and wiring of networks will continue to contribute to our overall understanding of the visual cortex.

Anxiety Evokes Hypofrontality and Disrupts Rule-Relevant Encoding by Dorsomedial Prefrontal Cortex Neurons.

PubMed

Park, Junchol; Wood, Jesse; Bondi, Corina; Del Arco, Alberto; Moghaddam, Bita

2016-03-16

Anxiety is a debilitating symptom of most psychiatric disorders, including major depression, post-traumatic stress disorder, schizophrenia, and addiction. A detrimental aspect of anxiety is disruption of prefrontal cortex (PFC)-mediated executive functions, such as flexible decision making. Here we sought to understand how anxiety modulates PFC neuronal encoding of flexible shifting between behavioral strategies. We used a clinically substantiated anxiogenic treatment to induce sustained anxiety in rats and recorded from dorsomedial PFC (dmPFC) and orbitofrontal cortex (OFC) neurons while they were freely moving in a home cage and while they performed a PFC-dependent task that required flexible switches between rules in two distinct perceptual dimensions. Anxiety elicited a sustained background "hypofrontality" in dmPFC and OFC by reducing the firing rate of spontaneously active neuronal subpopulations. During task performance, the impact of anxiety was subtle, but, consistent with human data, behavior was selectively impaired when previously correct conditions were presented as conflicting choices. This impairment was associated with reduced recruitment of dmPFC neurons that selectively represented task rules at the time of action. OFC rule representation was not affected by anxiety. These data indicate that a neural substrate of the decision-making deficits in anxiety is diminished dmPFC neuronal encoding of task rules during conflict-related actions. Given the translational relevance of the model used here, the data provide a neuronal encoding mechanism for how anxiety biases decision making when the choice involves overcoming a conflict. They also demonstrate that PFC encoding of actions, as opposed to cues or outcome, is especially vulnerable to anxiety. A debilitating aspect of anxiety is its impact on decision making and flexible control of behavior. These cognitive constructs depend on proper functioning of the prefrontal cortex (PFC). Understanding how anxiety affects PFC encoding of cognitive events is of great clinical and evolutionary significance. Using a clinically valid experimental model, we find that, under anxiety, decision making may be skewed by salient and conflicting environmental stimuli at the expense of flexible top-down guided choices. We also find that anxiety suppresses spontaneous activity of PFC neurons, and weakens encoding of task rules by dorsomedial PFC neurons. These data provide a neuronal encoding scheme for how anxiety disengages PFC during decision making. Copyright © 2016 the authors 0270-6474/16/363322-14$15.00/0.

Cerebral cortical neurons with activity linked to central neurogenic spontaneous and evoked elevations in cerebral blood flow

NASA Technical Reports Server (NTRS)

Golanov, E. V.; Reis, D. J.

1996-01-01

We recorded neurons in rat cerebral cortex with activity relating to the neurogenic elevations in regional cerebral blood flow (rCBF) coupled to stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes, appearing spontaneously or evoked by electrical stimulation of rostral ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously active neurons only 15 (5%), in layers 5-6, consistently (P < 0.05, chi-square) increased their activity during the earliest potential of the complex, approximately 1.3 s before the rise of rCBF, and during the minutes-long elevation of rCBF elicited by 10 s of stimulation of RVL or FN. The results indicate the presence of a small population of neurons in deep cortical laminae whose activity correlates with neurogenic elevations of rCBF. These neurons may function to transduce afferent neuronal signals into vasodilation.

RIPK3/MLKL-Mediated Neuronal Necroptosis Modulates the M1/M2 Polarization of Microglia/Macrophages in the Ischemic Cortex

PubMed Central

Yang, Jiping; Zhao, Youyi; Zhang, Li; Fan, Hong; Qi, Chuchu; Zhang, Kun; Liu, Xinyu; Fei, Lin; Chen, Siwei; Wang, Mengmeng; Kuang, Fang; Wang, Yazhou; Wu, Shengxi

2018-01-01

Abstract Cell death and subsequent inflammation are 2 key pathological changes occurring in cerebral ischemia. Active microglia/macrophages play a double-edged role depending on the balance of their M1/M2 phenotypes. Necrosis is the predominant type of cell death following ischemia. However, how necrotic cells modulate the M1/M2 polarization of microglia/macrophages remains poorly investigated. Here, we reported that ischemia induces a rapid RIPK3/MLKL-mediated neuron-dominated necroptosis, a type of programmed necrosis. Ablating RIPK3 or MLKL could switch the activation of microglia/macrophages from M1 to the M2 type in the ischemic cortex. Conditioned medium of oxygen-glucose deprivation (OGD)-treated wild-type (WT) neurons induced M1 polarization, while that of RIPK3−/− neurons favored M2 polarization. OGD treatment induces proinflammatory IL-18 and TNFα in WT but not in RIPK3−/− neurons, which in turn upregulate anti-inflammatory IL-4 and IL-10. Furthermore, the expression of Myd88—a common downstream adaptor of toll-like receptors—is significantly upregulated in the microglia/macrophages of ischemic WT but not of RIPK3−/− or MLKL−/− cortices. Antagonizing the function of Myd88 could phenocopy the effects of RIPK3/MLKL-knockout on the polarization of microglia/macrophages and was neuroprotective. Our data revealed a novel role of necroptotic neurons in modulating the M1/M2 balance of microglia/macrophages in the ischemic cortex, possibly through Myd88 signaling. PMID:29746630

Tocilizumab inhibits neuronal cell apoptosis and activates STAT3 in cerebral infarction rat model.

PubMed

Wang, Shaojun; Zhou, Jun; Kang, Weijie; Dong, Zhaoni; Wang, Hezuo

2016-01-15

Cerebral infarction is a severe hypoxic ischemic necrosis with accelerated neuronal cell apoptosis in the brain. As a monoclonal antibody against interleukin 6, tocilizumab (TCZ) is widely used in immune diseases, whose function in cerebral infarction has not been studied. This study aims to reveal the role of TCZ in regulating neuronal cell apoptosis in cerebral infarction. The cerebral infarction rat model was constructed by middle cerebral artery occlusion and treated with TCZ. Cell apoptosis in hippocampus and cortex of the brain was examined with TUNEL method. Rat neuronal cells cultured in oxygen-glucose deprivation (OGD) conditions and treated with TCZ were used to compare cell viability and apoptosis. Apoptosis-related factors including B-cell lymphoma extra large (Bcl-xL) and Caspase 3, as well as the phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in brain cortex were analyzed from the protein level. Results indicated that TCZ treatment could significantly prevent the promoted cell apoptosis caused by cerebral infarction or OGD (P < 0.05 or P < 0.01). In brain cortex of the rat model, TCZ up-regulated Bcl-xL and down-regulated Caspase 3, consistent with the inhibited cell apoptosis. It also promoted tyrosine 705 phosphorylation of STAT3, which might be the potential regulatory mechanism of TCZ in neuronal cells. This study provided evidence for the protective role of TCZ against neuronal cell apoptosis in cerebral infarction. Based on these fundamental data, TCZ is a promising option for treating cerebral infarction, but further investigations on related mechanisms are still necessary.

Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

PubMed Central

Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

2015-01-01

Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism.

PubMed

Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John D R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

2015-04-23

Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.

Activation of cannabinoid system in anterior cingulate cortex and orbitofrontal cortex modulates cost-benefit decision making.

PubMed

Khani, Abbas; Kermani, Mojtaba; Hesam, Soghra; Haghparast, Abbas; Argandoña, Enrike G; Rainer, Gregor

2015-06-01

Despite the evidence for altered decision making in cannabis abusers, the role of the cannabinoid system in decision-making circuits has not been studied. Here, we examined the effects of cannabinoid modulation during cost-benefit decision making in the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), key brain areas involved in decision making. We trained different groups of rats in a delay-based and an effort-based form of cost-benefit T-maze decision-making task. During test days, the rats received local injections of either vehicle or ACEA, a cannabinoid type-1 receptor (CB1R) agonist in the ACC or OFC. We measured spontaneous locomotor activity following the same treatments and characterized CB1Rs localization on different neuronal populations within these regions using immunohistochemistry. We showed that CB1R activation in the ACC impaired decision making such that rats were less willing to invest physical effort to gain high reward. Similarly, CB1R activation in the OFC induced impulsive pattern of choice such that rats preferred small immediate rewards to large delayed rewards. Control tasks ensured that the effects were specific for differential cost-benefit tasks. Furthermore, we characterized widespread colocalizations of CB1Rs on GABAergic axonal ends but few colocalizations on glutamatergic, dopaminergic, and serotonergic neuronal ends. These results provide first direct evidence that the cannabinoid system plays a critical role in regulating cost-benefit decision making in the ACC and OFC and implicate cannabinoid modulation of synaptic ends of predominantly interneurons and to a lesser degree other neuronal populations in these two frontal regions.

Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT)

PubMed Central

Blackman, Rachael K.; Crowe, David A.; DeNicola, Adele L.; Sakellaridi, Sofia; MacDonald, Angus W.

2016-01-01

Cognitive control is the ability to modify the behavioral response to a stimulus based on internal representations of goals or rules. We sought to characterize neural mechanisms in prefrontal cortex associated with cognitive control in a context that would maximize the potential for future translational relevance to human neuropsychiatric disease. To that end, we trained monkeys to perform a dot-pattern variant of the AX continuous performance task that is used to measure cognitive control impairment in patients with schizophrenia (MacDonald, 2008; Jones et al., 2010). Here we describe how information processing for cognitive control in this task is related to neural activity patterns in prefrontal cortex of monkeys, to advance our understanding of how behavioral flexibility is implemented by prefrontal neurons in general, and to model neural signals in the healthy brain that may be disrupted to produce cognitive control deficits in schizophrenia. We found that the neural representation of stimuli in prefrontal cortex is strongly biased toward stimuli that inhibit prepotent or automatic responses. We also found that population signals encoding different stimuli were modulated to overlap in time specifically in the case that information from multiple stimuli had to be integrated to select a conditional response. Finally, population signals relating to the motor response were biased toward less frequent and therefore less automatic actions. These data relate neuronal activity patterns in prefrontal cortex to logical information processing operations required for cognitive control, and they characterize neural events that may be disrupted in schizophrenia. SIGNIFICANCE STATEMENT Functional imaging studies have demonstrated that cognitive control deficits in schizophrenia are associated with reduced activation of the dorsolateral prefrontal cortex (MacDonald et al., 2005). However, these data do not reveal how the disease has disrupted the function of prefrontal neurons to produce the observed deficits in cognitive control. Relating cognitive control to neurophysiological signals at a cellular level in prefrontal cortex is a necessary first step toward understanding how disruption of these signals could lead to cognitive control failure in neuropsychiatric disease. To that end, we translated a task that measures cognitive control deficits in patients with schizophrenia to monkeys and describe here how neural signals in prefrontal cortex relate to performance. PMID:27053213

Ghrelin Causes a Decline in GABA Release by Reducing Fatty Acid Oxidation in Cortex.

PubMed

Mir, Joan Francesc; Zagmutt, Sebastián; Lichtenstein, Mathieu P; García-Villoria, Judit; Weber, Minéia; Gracia, Ana; Fabriàs, Gemma; Casas, Josefina; López, Miguel; Casals, Núria; Ribes, Antònia; Suñol, Cristina; Herrero, Laura; Serra, Dolors

2018-02-02

Lipid metabolism, specifically fatty acid oxidation (FAO) mediated by carnitine palmitoyltransferase (CPT) 1A, has been described to be an important actor of ghrelin action in hypothalamus. However, it is not known whether CPT1A and FAO mediate the effect of ghrelin on the cortex. Here, we show that ghrelin produces a differential effect on CPT1 activity and γ-aminobutyric acid (GABA) metabolism in the hypothalamus and cortex of mice. In the hypothalamus, ghrelin enhances CPT1A activity while GABA transaminase (GABAT) activity, a key enzyme in GABA shunt metabolism, is unaltered. However, in cortex CPT1A activity and GABAT activity are reduced after ghrelin treatment. Furthermore, in primary cortical neurons, ghrelin reduces GABA release through a CPT1A reduction. By using CPT1A floxed mice, we have observed that genetic ablation of CPT1A recapitulates the effect of ghrelin on GABA release in cortical neurons, inducing reductions in mitochondrial oxygen consumption, cell content of citrate and α-ketoglutarate, and GABA shunt enzyme activity. Taken together, these observations indicate that ghrelin-induced changes in CPT1A activity modulate mitochondrial function, yielding changes in GABA metabolism. This evidence suggests that the action of ghrelin on GABA release is region specific within the brain, providing a basis for differential effects of ghrelin in the central nervous system.

Nicotinic α5 Subunits Drive Developmental Changes in the Activation and Morphology of Prefrontal Cortex Layer VI Neurons

PubMed Central

Bailey, Craig D.C.; Alves, Nyresa C.; Nashmi, Raad; De Biasi, Mariella; Lambe, Evelyn K.

2013-01-01

Background Nicotinic signaling in prefrontal layer VI pyramidal neurons is important to the function of mature attention systems. The normal incorporation of α5 subunits into α4β2* nicotinic acetylcholine receptors augments nicotinic signaling in these neurons and is required for normal attention performance in adult mice. However, the role of α5 subunits in the development of the prefrontal cortex is not known. Methods We sought to answer this question by examining nicotinic currents and neuronal morphology in layer VI neurons of medial prefrontal cortex of wild-type and α5 subunit knockout (α5−/−) mice during postnatal development and in adulthood. Results In wild-type but not in α5−/− mice, there is a developmental peak in nicotinic acetylcholine currents in the third postnatal week. At this juvenile time period, the majority of neurons in all mice have long apical dendrites extending into cortical layer I. Yet, by early adulthood, wild-type but not α5−/− mice show a pronounced shift toward shorter apical dendrites. This cellular difference occurs in the absence of genotype differences in overall cortical morphology. Conclusions Normal developmental changes in nicotinic signaling and dendritic morphology in prefrontal cortex depend on α5-comprising nicotinic acetylcholine receptors. It appears that these receptors mediate a specific developmental retraction of apical dendrites in layer VI neurons. This finding provides novel insight into the cellular mechanisms underlying the known attention deficits in α5−/− mice and potentially also into the pathophysiology of developmental neuropsychiatric disorders such as attention-deficit disorder and autism. PMID:22030359

[Morphological and laminar distribution of cholecystokinin-immunoreactive neurons in cortex of human inferior parietal lobe and their clinical significance].

PubMed

Puskas, Laslo; Draganić-Gajić, Saveta; Malobabić, Slobodan; Puskas, Nela; Krivokuća, Dragan; Stanković, Gordana

2008-01-01

Cholecystocinine is a neuropeptide whose function in the cortex has not yet been clarified, although its relation with some psychic disorders has been noticed. Previous studies have not provided detailed data about types, or arrangement of neurons that contain those neuropeptide in the cortex of human inferior parietal lobe. The aim of this study was to examine precisely the morphology and typography of neurons containing cholecytocinine in the human cortex of inferior parietal lobule. There were five human brains on which we did the immunocystochemical research of the shape and laminar distribution of cholecystocinine immunoreactive neurons on serial sections of supramarginal gyrus and angular gyrus. The morphological analysis of cholecystocinine-immunoreactive neurons was done on frozen sections using avidin-biotin technique, by antibody to cholecystocinine diluted in the proportion 1:6000 using diamine-benzedine. Cholecystocinine immunoreactive neurons were found in the first three layers of the cortex of inferior parietal lobule, and their densest concentration was in the 2nd and 3rd layer. The following types of neurons were found: bipolar neurons, then its fusiform subtype, Cajal-Retzius neurons (in the 1st layer), reverse pyramidal (triangular) and unipolar neurons. The diameters of some types of neurons were from 15 to 35 microm, and the diameters of dendritic arborization were from 85-207 microm. A special emphasis is put on the finding of Cajal-Retzius neurons that are immunoreactive to cholecystocinine, which demands further research. Bearing in mind numerous clinical studies pointing out the role of cholecystokinine in the pathogenesis of schizophrenia, the presence of a great number of cholecystokinine immunoreactive neurons in the cortex of inferior parietal lobule suggests their role in the pathogenesis of schizophrenia.

The Role of Dopamine in Normal Rodent Motor Cortex: Physiological Effects and Structural Correlates

DTIC Science & Technology

1999-04-05

things she does on a daily basis made the lab a great place to do research. Susan’s expertise in molecular techniques was evident from day one , and I...applied OA on the spontaneous activity (SA) of PTNs. the receptors that mediate these effects, and DA’s effects on glutamate induced excitation of PTNs...numerous neurons in the motor cortex and may have profound effects on motor cortex activity, through its influence on PTNs. iv The Role of Dopamine in

Self-sustained asynchronous irregular states and Up-Down states in thalamic, cortical and thalamocortical networks of nonlinear integrate-and-fire neurons.

PubMed

Destexhe, Alain

2009-12-01

Randomly-connected networks of integrate-and-fire (IF) neurons are known to display asynchronous irregular (AI) activity states, which resemble the discharge activity recorded in the cerebral cortex of awake animals. However, it is not clear whether such activity states are specific to simple IF models, or if they also exist in networks where neurons are endowed with complex intrinsic properties similar to electrophysiological measurements. Here, we investigate the occurrence of AI states in networks of nonlinear IF neurons, such as the adaptive exponential IF (Brette-Gerstner-Izhikevich) model. This model can display intrinsic properties such as low-threshold spike (LTS), regular spiking (RS) or fast-spiking (FS). We successively investigate the oscillatory and AI dynamics of thalamic, cortical and thalamocortical networks using such models. AI states can be found in each case, sometimes with surprisingly small network size of the order of a few tens of neurons. We show that the presence of LTS neurons in cortex or in thalamus, explains the robust emergence of AI states for relatively small network sizes. Finally, we investigate the role of spike-frequency adaptation (SFA). In cortical networks with strong SFA in RS cells, the AI state is transient, but when SFA is reduced, AI states can be self-sustained for long times. In thalamocortical networks, AI states are found when the cortex is itself in an AI state, but with strong SFA, the thalamocortical network displays Up and Down state transitions, similar to intracellular recordings during slow-wave sleep or anesthesia. Self-sustained Up and Down states could also be generated by two-layer cortical networks with LTS cells. These models suggest that intrinsic properties such as adaptation and low-threshold bursting activity are crucial for the genesis and control of AI states in thalamocortical networks.

Learning-induced Dependence of Neuronal Activity in Primary Motor Cortex on Motor Task Condition.

PubMed

Cai, X; Shimansky, Y; He, Jiping

2005-01-01

A brain-computer interface (BCI) system such as a cortically controlled robotic arm must have a capacity of adjusting its function to a specific environmental condition. We studied this capacity in non-human primates based on chronic multi-electrode recording from the primary motor cortex of a monkey during the animal's performance of a center-out 3D reaching task and adaptation to external force perturbations. The main condition-related feature of motor cortical activity observed before the onset of force perturbation was a phasic raise of activity immediately before the perturbation onset. This feature was observed during a series of perturbation trials, but were absent under no perturbations. After adaptation has been completed, it usually was taking the subject only one trial to recognize a change in the condition to switch the neuronal activity accordingly. These condition-dependent features of neuronal activity can be used by a BCI for recognizing a change in the environmental condition and making corresponding adjustments, which requires that the BCI-based control system possess such advanced properties of the neural motor control system as capacity to learn and adapt.

Neural Correlation Is Stimulus Modulated by Feedforward Inhibitory Circuitry

PubMed Central

Middleton, Jason W.; Omar, Cyrus; Doiron, Brent; Simons, Daniel J.

2012-01-01

Correlated variability of neural spiking activity has important consequences for signal processing. How incoming sensory signals shape correlations of population responses remains unclear. Cross-correlations between spiking of different neurons may be particularly consequential in sparsely firing neural populations such as those found in layer 2/3 of sensory cortex. In rat whisker barrel cortex, we found that pairs of excitatory layer 2/3 neurons exhibit similarly low levels of spike count correlation during both spontaneous and sensory-evoked states. The spontaneous activity of excitatory–inhibitory neuron pairs is positively correlated, while sensory stimuli actively decorrelate joint responses. Computational modeling shows how threshold nonlinearities and local inhibition form the basis of a general decorrelating mechanism. We show that inhibitory population activity maintains low correlations in excitatory populations, especially during periods of sensory-evoked coactivation. The role of feedforward inhibition has been previously described in the context of trial-averaged phenomena. Our findings reveal a novel role for inhibition to shape correlations of neural variability and thereby prevent excessive correlations in the face of feedforward sensory-evoked activation. PMID:22238086

Neuronal representation of individual heroin choices in the orbitofrontal cortex.

PubMed

Guillem, Karine; Brenot, Viridiana; Durand, Audrey; Ahmed, Serge H

2018-05-01

Drug addiction is a harmful preference for drug use over and at the expense of other non-drug-related activities. We previously identified in the rat orbitofrontal cortex (OFC) a mechanism that influences individual preferences between cocaine use and an alternative action rewarded by a non-drug reward (i.e. sweet water). Here, we sought to test the generality of this mechanism to a different addictive drug, heroin. OFC neuronal activity was recorded while rats responded for heroin or the alternative non-drug reward separately or while they chose between the two. First, we found that heroin-rewarded and sweet water-rewarded actions were encoded by two non-overlapping OFC neuronal populations and that the relative size of the heroin population represented individual drug choices. Second, OFC neurons encoding the preferred action-which was the non-drug action in the large majority of individuals-progressively fired more than non-preferred action-coding neurons 1 second after the onset of choice trials and around 1 second before the preferred action was actually chosen, suggesting a pre-choice neuronal competition for action selection. Together with a previous study on cocaine choice, the present study on heroin choice reveals important commonalities in how OFC neurons encode individual drug choices and preferences across different classes of drugs. It also reveals some drug-specific differences in OFC encoding activity. Notably, the proportion of neurons that non-selectively encode both the drug and the non-drug reward was higher when the drug was heroin (present study) than when it was cocaine (previous study). We will discuss the potential functional significance of these commonalities and differences in OFC neuronal activity across different drugs for understanding drug choice. © 2017 Society for the Study of Addiction.

Negative BOLD with Large Increases in Neuronal Activity

PubMed Central

Khubchandani, Manjula; Motelow, Joshua E.; Sanganahalli, Basavaraju G.; Hyder, Fahmeed

2008-01-01

Blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used in neuroscience to study brain activity. However, BOLD fMRI does not measure neuronal activity directly but depends on cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) consumption. Using fMRI, CBV, CBF, neuronal recordings, and CMRO2 modeling, we investigated how the signals are related during seizures in rats. We found that increases in hemodynamic, neuronal, and metabolic activity were associated with positive BOLD signals in the cortex, but with negative BOLD signals in hippocampus. Our data show that negative BOLD signals do not necessarily imply decreased neuronal activity or CBF, but can result from increased neuronal activity, depending on the interplay between hemodynamics and metabolism. Caution should be used in interpreting fMRI signals because the relationship between neuronal activity and BOLD signals may depend on brain region and state and can be different during normal and pathological conditions. PMID:18063563

Potential role of monkey inferior parietal neurons coding action semantic equivalences as precursors of parts of speech.

PubMed

Yamazaki, Yumiko; Yokochi, Hiroko; Tanaka, Michio; Okanoya, Kazuo; Iriki, Atsushi

2010-01-01

The anterior portion of the inferior parietal cortex possesses comprehensive representations of actions embedded in behavioural contexts. Mirror neurons, which respond to both self-executed and observed actions, exist in this brain region in addition to those originally found in the premotor cortex. We found that parietal mirror neurons responded differentially to identical actions embedded in different contexts. Another type of parietal mirror neuron represents an inverse and complementary property of responding equally to dissimilar actions made by itself and others for an identical purpose. Here, we propose a hypothesis that these sets of inferior parietal neurons constitute a neural basis for encoding the semantic equivalence of various actions across different agents and contexts. The neurons have mirror neuron properties, and they encoded generalization of agents, differentiation of outcomes, and categorization of actions that led to common functions. By integrating the activities of these mirror neurons with various codings, we further suggest that in the ancestral primates' brains, these various representations of meaningful action led to the gradual establishment of equivalence relations among the different types of actions, by sharing common action semantics. Such differential codings of the components of actions might represent precursors to the parts of protolanguage, such as gestural communication, which are shared among various members of a society. Finally, we suggest that the inferior parietal cortex serves as an interface between this action semantics system and other higher semantic systems, through common structures of action representation that mimic language syntax.

Potential role of monkey inferior parietal neurons coding action semantic equivalences as precursors of parts of speech

PubMed Central

Yamazaki, Yumiko; Yokochi, Hiroko; Tanaka, Michio; Okanoya, Kazuo; Iriki, Atsushi

2010-01-01

The anterior portion of the inferior parietal cortex possesses comprehensive representations of actions embedded in behavioural contexts. Mirror neurons, which respond to both self-executed and observed actions, exist in this brain region in addition to those originally found in the premotor cortex. We found that parietal mirror neurons responded differentially to identical actions embedded in different contexts. Another type of parietal mirror neuron represents an inverse and complementary property of responding equally to dissimilar actions made by itself and others for an identical purpose. Here, we propose a hypothesis that these sets of inferior parietal neurons constitute a neural basis for encoding the semantic equivalence of various actions across different agents and contexts. The neurons have mirror neuron properties, and they encoded generalization of agents, differentiation of outcomes, and categorization of actions that led to common functions. By integrating the activities of these mirror neurons with various codings, we further suggest that in the ancestral primates' brains, these various representations of meaningful action led to the gradual establishment of equivalence relations among the different types of actions, by sharing common action semantics. Such differential codings of the components of actions might represent precursors to the parts of protolanguage, such as gestural communication, which are shared among various members of a society. Finally, we suggest that the inferior parietal cortex serves as an interface between this action semantics system and other higher semantic systems, through common structures of action representation that mimic language syntax. PMID:20119879

Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

PubMed

Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

2017-09-09

In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

Why does serotonergic activity drastically decrease during REM sleep?

PubMed

Sato, Kohji

2013-10-01

Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation. Copyright © 2013. Published by Elsevier Ltd.

NADPH-diaphorase activity and neurovascular coupling in the rat cerebral cortex.

PubMed

Vlasenko, O V; Maisky, V A; Maznychenko, A V; Pilyavskii, A I

2008-01-01

The distribution of NADPH-diaphorase-reactive (NADPH-dr) neurons and neuronal processes in the cerebral cortex and basal forebrain and their association with parenchymal vessels were studied in normal adult rats using NADPH-d histochemical protocol. The intensely stained cortical interneurons and reactive subcortically originating afferents, and stained microvessels were examined through a light microscope at law (x250) and high (x630) magnifications. NADPH-dr interneurons were concentrated in layers 2-6 of the M1 and M2 areas. However, clear predominance in their concentration (14 +/- 0.8 P < 0.05 per section) was found in layer 6. A mean number of labeled neurons in auditory (AuV), granular and agranular (GI, AIP) areas of the insular cortex was calculated to reach 12.3 +/- 0.7, 18.5 +/- 1.0 and 23.3 +/- 1.7 units per section, respectively (P < 0.05). The distinct apposition of labelled neurons to intracortical vessels was found in the M1, M2. The order of frequency of neurovascular coupling in different zones of the cerebral cortex was as following sequence: AuV (31.2%, n = 1040) > GI (18.0%, n = 640) > S1 (13.3%, n = 720) > M1 (6.3%, n = 1360). A large number of structural associations between labeled cells and vessels in the temporal and insular cortex indicate that NADPH-d-reactive interneurons can contribute to regulation of the cerebral regional blood flow in these areas.

Diversity of layer 5 projection neurons in the mouse motor cortex

PubMed Central

Oswald, Manfred J.; Tantirigama, Malinda L. S.; Sonntag, Ivo; Hughes, Stephanie M.; Empson, Ruth M.

2013-01-01

In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labeled M1 corticospinal (CSp), corticothalamic (CTh), and commissural projecting corticostriatal (CStr) and corticocortical (CC) neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP) waveform, firing behavior, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behavior in corticofugal neurons. At 26°C CTh neurons fired bursts of APs more often than CSp neurons, but at 36°C both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function. PMID:24137110

Localized Disruption of Narp in Medial Prefrontal Cortex Blocks Reinforcer Devaluation Performance

ERIC Educational Resources Information Center

Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.

2010-01-01

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates [alpha]-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this…

Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution

PubMed Central

Herculano-Houzel, Suzana

2011-01-01

It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution. PMID:21390261

Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution.

PubMed

Herculano-Houzel, Suzana

2011-03-01

It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

PubMed

Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2016-02-01

Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the sub-chronic PCP model of schizophrenia

PubMed Central

Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

2017-01-01

Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the CSF levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared to THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. PMID:26510449

Somato-Motor Haptic Processing in Posterior Inner Perisylvian Region (SII/pIC) of the Macaque Monkey

PubMed Central

Ishida, Hiroaki; Fornia, Luca; Grandi, Laura Clara; Umiltà, Maria Alessandra; Gallese, Vittorio

2013-01-01

The posterior inner perisylvian region including the secondary somatosensory cortex (area SII) and the adjacent region of posterior insular cortex (pIC) has been implicated in haptic processing by integrating somato-motor information during hand-manipulation, both in humans and in non-human primates. However, motor-related properties during hand-manipulation are still largely unknown. To investigate a motor-related activity in the hand region of SII/pIC, two macaque monkeys were trained to perform a hand-manipulation task, requiring 3 different grip types (precision grip, finger exploration, side grip) both in light and in dark conditions. Our results showed that 70% (n = 33/48) of task related neurons within SII/pIC were only activated during monkeys’ active hand-manipulation. Of those 33 neurons, 15 (45%) began to discharge before hand-target contact, while the remaining neurons were tonically active after contact. Thirty-percent (n = 15/48) of studied neurons responded to both passive somatosensory stimulation and to the motor task. A consistent percentage of task-related neurons in SII/pIC was selectively activated during finger exploration (FE) and precision grasping (PG) execution, suggesting they play a pivotal role in control skilled finger movements. Furthermore, hand-manipulation-related neurons also responded when visual feedback was absent in the dark. Altogether, our results suggest that somato-motor neurons in SII/pIC likely contribute to haptic processing from the initial to the final phase of grasping and object manipulation. Such motor-related activity could also provide the somato-motor binding principle enabling the translation of diachronic somatosensory inputs into a coherent image of the explored object. PMID:23936121

Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.

PubMed

Bifari, Francesco; Decimo, Ilaria; Pino, Annachiara; Llorens-Bobadilla, Enric; Zhao, Sheng; Lange, Christian; Panuccio, Gabriella; Boeckx, Bram; Thienpont, Bernard; Vinckier, Stefan; Wyns, Sabine; Bouché, Ann; Lambrechts, Diether; Giugliano, Michele; Dewerchin, Mieke; Martin-Villalba, Ana; Carmeliet, Peter

2017-03-02

Whether new neurons are added in the postnatal cerebral cortex is still debated. Here, we report that the meninges of perinatal mice contain a population of neurogenic progenitors formed during embryonic development that migrate to the caudal cortex and differentiate into Satb2 + neurons in cortical layers II-IV. The resulting neurons are electrically functional and integrated into local microcircuits. Single-cell RNA sequencing identified meningeal cells with distinct transcriptome signatures characteristic of (1) neurogenic radial glia-like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3) a cell type with an intermediate phenotype, possibly representing radial glia-like meningeal cells differentiating to neuronal cells. Thus, we have identified a pool of embryonically derived radial glia-like cells present in the meninges that migrate and differentiate into functional neurons in the neonatal cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

The neuronal correlates of mirror therapy: an fMRI study on mirror induced visual illusions in patients with stroke.

PubMed

Michielsen, Marian E; Smits, Marion; Ribbers, Gerard M; Stam, Henk J; van der Geest, Jos N; Bussmann, Johannes B J; Selles, Ruud W

2011-04-01

To investigate the neuronal basis for the effects of mirror therapy in patients with stroke. 22 patients with stroke participated in this study. The authors used functional MRI to investigate neuronal activation patterns in two experiments. In the unimanual experiment, patients moved their unaffected hand, either while observing it directly (no-mirror condition) or while observing its mirror reflection (mirror condition). In the bimanual experiment, patients moved both hands, either while observing the affected hand directly (no-mirror condition) or while observing the mirror reflection of the unaffected hand in place of the affected hand (mirror condition). A two-factorial analysis with movement (activity vs rest) and mirror (mirror vs no mirror) as main factors was performed to assess neuronal activity resultant of the mirror illusion. Data on 18 participants were suitable for analysis. Results showed a significant interaction effect of movement×mirror during the bimanual experiment. Activated regions were the precuneus and the posterior cingulate cortex (p<0.05 false discovery rate). In this first study on the neuronal correlates of the mirror illusion in patients with stroke, the authors showed that during bimanual movement, the mirror illusion increases activity in the precuneus and the posterior cingulate cortex, areas associated with awareness of the self and spatial attention. By increasing awareness of the affected limb, the mirror illusion might reduce learnt non-use. The fact that the authors did not observe mirror-related activity in areas of the motor or mirror neuron system questions popular theories that attribute the clinical effects of mirror therapy to these systems.

Neuronal avalanches of a self-organized neural network with active-neuron-dominant structure.

PubMed

Li, Xiumin; Small, Michael

2012-06-01

Neuronal avalanche is a spontaneous neuronal activity which obeys a power-law distribution of population event sizes with an exponent of -3/2. It has been observed in the superficial layers of cortex both in vivo and in vitro. In this paper, we analyze the information transmission of a novel self-organized neural network with active-neuron-dominant structure. Neuronal avalanches can be observed in this network with appropriate input intensity. We find that the process of network learning via spike-timing dependent plasticity dramatically increases the complexity of network structure, which is finally self-organized to be active-neuron-dominant connectivity. Both the entropy of activity patterns and the complexity of their resulting post-synaptic inputs are maximized when the network dynamics are propagated as neuronal avalanches. This emergent topology is beneficial for information transmission with high efficiency and also could be responsible for the large information capacity of this network compared with alternative archetypal networks with different neural connectivity.

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

Cognitive processing in the primary visual cortex: from perception to memory.

PubMed

Supèr, Hans

2002-01-01

The primary visual cortex is the first cortical area of the visual system that receives information from the external visual world. Based on the receptive field characteristics of the neurons in this area, it has been assumed that the primary visual cortex is a pure sensory area extracting basic elements of the visual scene. This information is then subsequently further processed upstream in the higher-order visual areas and provides us with perception and storage of the visual environment. However, recent findings show that such neural implementations are observed in the primary visual cortex. These neural correlates are expressed by the modulated activity of the late response of a neuron to a stimulus, and most likely depend on recurrent interactions between several areas of the visual system. This favors the concept of a distributed nature of visual processing in perceptual organization.

Cortical ensemble activity increasingly predicts behaviour outcomes during learning of a motor task

NASA Astrophysics Data System (ADS)

Laubach, Mark; Wessberg, Johan; Nicolelis, Miguel A. L.

2000-06-01

When an animal learns to make movements in response to different stimuli, changes in activity in the motor cortex seem to accompany and underlie this learning. The precise nature of modifications in cortical motor areas during the initial stages of motor learning, however, is largely unknown. Here we address this issue by chronically recording from neuronal ensembles located in the rat motor cortex, throughout the period required for rats to learn a reaction-time task. Motor learning was demonstrated by a decrease in the variance of the rats' reaction times and an increase in the time the animals were able to wait for a trigger stimulus. These behavioural changes were correlated with a significant increase in our ability to predict the correct or incorrect outcome of single trials based on three measures of neuronal ensemble activity: average firing rate, temporal patterns of firing, and correlated firing. This increase in prediction indicates that an association between sensory cues and movement emerged in the motor cortex as the task was learned. Such modifications in cortical ensemble activity may be critical for the initial learning of motor tasks.

[The negative side of emotions: addiction to drugs of abuse].

PubMed

Contreras, M; Ceric, F; Torrealba, F

According to the model of emotions, feelings have their origin in the conscious perception of body changes produced in response to an emotional stimulus. These changes are perceived thanks to the fact that they are represented in the brain by the interoceptive system. During abstinence, addicts experience intense feelings of ill-being that drive them to consume drugs. The purpose of this review is to discuss the role played by the interoceptive system, and more especially the insular cortex, in the perception of the negative feelings that characterise abstinence. The continuous processing of interoceptive signals in the insular cortex is what accounts for the conscious appreciation of the body changes that accompany an emotional state. Temporary inactivation of the insular cortex suppresses the search for drugs in addicted rats. Neuroimaging studies reveal an increase in the neuronal activity in the insular cortex and in other areas of the brain while addicts are experiencing the craving to consume drugs. Likewise, nicotine addicts who suffer a brain injury that affects the insular cortex give up smoking easily because they lose the desire to do it. The temporary suppression of neuronal activity in the insular cortex in human addicts by means of non-invasive techniques could be a new therapy to treat the craving to consume drugs. The insular cortex is essential in the perception of the emotional states and in orienting behaviour to match the needs of the body. New therapies that have the insular cortex as their target could be developed to mitigate craving.

Transcranial magnetic stimulation changes response selectivity of neurons in the visual cortex

PubMed Central

Kim, Taekjun; Allen, Elena A.; Pasley, Brian N.; Freeman, Ralph D.

2015-01-01

Background Transcranial magnetic stimulation (TMS) is used to selectively alter neuronal activity of specific regions in the cerebral cortex. TMS is reported to induce either transient disruption or enhancement of different neural functions. However, its effects on tuning properties of sensory neurons have not been studied quantitatively. Objective/Hypothesis Here, we use specific TMS application parameters to determine how they may alter tuning characteristics (orientation, spatial frequency, and contrast sensitivity) of single neurons in the cat’s visual cortex. Methods Single unit spikes were recorded with tungsten microelectrodes from the visual cortex of anesthetized and paralyzed cats (12 males). Repetitive TMS (4Hz, 4sec) was delivered with a 70mm figure-8 coil. We quantified basic tuning parameters of individual neurons for each pre- and post-TMS condition. The statistical significance of changes for each tuning parameter between the two conditions was evaluated with a Wilcoxon signed-rank test. Results We generally find long-lasting suppression which persists well beyond the stimulation period. Pre- and post-TMS orientation tuning curves show constant peak values. However, strong suppression at non-preferred orientations tends to narrow the widths of tuning curves. Spatial frequency tuning exhibits an asymmetric change in overall shape, which results in an emphasis on higher frequencies. Contrast tuning curves show nonlinear changes consistent with a gain control mechanism. Conclusions These findings suggest that TMS causes extended interruption of the balance between sub-cortical and intra-cortical inputs. PMID:25862599

Secondary damage in the spinal cord after motor cortex injury in rats.

PubMed

Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

2010-08-01

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

PubMed

Kim, Jinhyung; Ryu, Sang Baek; Lee, Sung Eun; Shin, Jaewoo; Jung, Hyun Ho; Kim, Sung June; Kim, Kyung Hwan; Chang, Jin Woo

2016-03-01

Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

Reward-timing-dependent bidirectional modulation of cortical microcircuits during optical single-neuron operant conditioning.

PubMed

Hira, Riichiro; Ohkubo, Fuki; Masamizu, Yoshito; Ohkura, Masamichi; Nakai, Junichi; Okada, Takashi; Matsuzaki, Masanori

2014-11-24

Animals rapidly adapt to environmental change. To reveal how cortical microcircuits are rapidly reorganized when an animal recognizes novel reward contingency, we conduct two-photon calcium imaging of layer 2/3 motor cortex neurons in mice and simultaneously reinforce the activity of a single cortical neuron with water delivery. Here we show that when the target neuron is not relevant to a pre-trained forelimb movement, the mouse increases the target neuron activity and the number of rewards delivered during 15-min operant conditioning without changing forelimb movement behaviour. The reinforcement bidirectionally modulates the activity of subsets of non-target neurons, independent of distance from the target neuron. The bidirectional modulation depends on the relative timing between the reward delivery and the neuronal activity, and is recreated by pairing reward delivery and photoactivation of a subset of neurons. Reward-timing-dependent bidirectional modulation may be one of the fundamental processes in microcircuit reorganization for rapid adaptation.

Neuronal activity in somatosensory cortex related to tactile exploration

PubMed Central

Fortier-Poisson, Pascal

2015-01-01

The very light contact forces (∼0.60 N) applied by the fingertips during tactile exploration reveal a clearly optimized sensorimotor strategy. To investigate the cortical mechanisms involved with this behavior, we recorded 230 neurons in the somatosensory cortex (S1), as two monkeys scanned different surfaces with the fingertips in search of a tactile target without visual feedback. During the exploration, the monkeys, like humans, carefully controlled the finger forces. High-friction surfaces offering greater tangential shear force resistance to the skin were associated with decreased normal contact forces. The activity of one group of neurons was modulated with either the normal or tangential force, with little or no influence from the orthogonal force component. A second group responded to kinetic friction or the ratio of tangential to normal forces rather than responding to a specific parameter, such as force magnitude or direction. A third group of S1 neurons appeared to respond to particular vectors of normal and tangential force on the skin. Although 45 neurons correlated with scanning speed, 32 were also modulated by finger forces, suggesting that forces on the finger should be considered as the primary parameter encoding the skin compliance and that finger speed is a secondary parameter that co-varies with finger forces. Neurons (102) were also tested with different textures, and the activity of 62 of these increased or decreased in relation to the surface friction. PMID:26467519

Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex.

PubMed

Chao, Dongman; Bazzy-Asaad, Alia; Balboni, Gianfranco; Salvadori, Severo; Xia, Ying

2008-09-01

We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K(+) homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K(+) homeostasis because the disruption of K(+) homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na(+) influx and thus stimulates K(+) leakage, we investigated whether DOR protects the cortex from anoxic K(+) derangement by targeting the Na(+)-based K(+) leakage. By using K(+)-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na(+) concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K(+) derangement; 2) lowering Na(+) concentration by substituting with permeable Li(+) tended to potentiate the anoxic K(+) derangement; and 3) the DOR-induced protection against the anoxic K(+) responses was largely abolished by low-Na(+) perfusion irrespective of the substituted cation. We conclude that external Na(+) concentration greatly influences anoxic K(+) derangement and that DOR activation likely attenuates anoxic K(+) derangement induced by the Na(+)-activated mechanisms in the cortex.

Multiple forebrain systems converge on motor neurons innervating the thyroarytenoid muscle

PubMed Central

Van Daele, Douglas J.; Cassell, Martin D.

2009-01-01

The present study investigated the central connections of motor neurons innervating the thyroarytenoid laryngeal muscle that is active in swallowing, respiration and vocalization. In both intact and sympathectomized rats, the pseudorabies virus (PRV) was inoculated into the muscle. After initial infection of laryngomotor neurons in the ipsilateral loose division of the nucleus ambiguous (NA) by 3 days post-inoculation., PRV spread to the ipsilateral compact portion of the NA, the central and intermediate divisions of the nucleus tractus solitarii (NTS), the Botzinger complex, and the parvocellular reticular formation by 4 days. Infection was subsequently expanded to include the ipsilateral granular and dysgranular parietal insular cortex, the ipsilateral medial division of the central nucleus of the amygdala, the lateral, paraventricular, ventrolateral and medial preoptic nuclei of the hypothalamus (generally bilaterally), the lateral periaqueductal gray, the A7 and oral and caudal pontine nuclei. At the latest time points sampled post-inoculation (5 days), infected neurons were identified in the ipsilateral agranular insular cortex, the caudal parietal insular cortex, the anterior cingulate cortex, and the contralateral motor cortex. In the amygdala, infection had spread to the lateral central nucleus and the parvocellular portion of the basolateral nucleus. Hypothalamic infection was largely characterized by an increase in the number of infected cells in earlier infected regions though the posterior, dorsomedial, tuberomammillary and mammillary nuclei contained infected cells. Comparison with previous connectional data suggest PRV followed three interconnected systems originating in the forebrain; a bilateral system including the ventral anterior cingulate cortex, periaqueductal gray and ventral respiratory group; an ipsilateral system involving the parietal insular cortex, central nucleus of the amygdala and parvicellular reticular formation, and a minor contralateral system originating in motor cortex. Hypothalamic innervation involved several functionally specific nuclei. Overall, the data imply complex central nervous system control over the multi-functional thyroarytenoid muscle.[297 words] PMID:19426785

Spatial processing in the auditory cortex of the macaque monkey

NASA Astrophysics Data System (ADS)

Recanzone, Gregg H.

2000-10-01

The patterns of cortico-cortical and cortico-thalamic connections of auditory cortical areas in the rhesus monkey have led to the hypothesis that acoustic information is processed in series and in parallel in the primate auditory cortex. Recent physiological experiments in the behaving monkey indicate that the response properties of neurons in different cortical areas are both functionally distinct from each other, which is indicative of parallel processing, and functionally similar to each other, which is indicative of serial processing. Thus, auditory cortical processing may be similar to the serial and parallel "what" and "where" processing by the primate visual cortex. If "where" information is serially processed in the primate auditory cortex, neurons in cortical areas along this pathway should have progressively better spatial tuning properties. This prediction is supported by recent experiments that have shown that neurons in the caudomedial field have better spatial tuning properties than neurons in the primary auditory cortex. Neurons in the caudomedial field are also better than primary auditory cortex neurons at predicting the sound localization ability across different stimulus frequencies and bandwidths in both azimuth and elevation. These data support the hypothesis that the primate auditory cortex processes acoustic information in a serial and parallel manner and suggest that this may be a general cortical mechanism for sensory perception.

A Simple Rule for Dendritic Spine and Axonal Bouton Formation Can Account for Cortical Reorganization after Focal Retinal Lesions

PubMed Central

Butz, Markus; van Ooyen, Arjen

2013-01-01

Lasting alterations in sensory input trigger massive structural and functional adaptations in cortical networks. The principles governing these experience-dependent changes are, however, poorly understood. Here, we examine whether a simple rule based on the neurons' need for homeostasis in electrical activity may serve as driving force for cortical reorganization. According to this rule, a neuron creates new spines and boutons when its level of electrical activity is below a homeostatic set-point and decreases the number of spines and boutons when its activity exceeds this set-point. In addition, neurons need a minimum level of activity to form spines and boutons. Spine and bouton formation depends solely on the neuron's own activity level, and synapses are formed by merging spines and boutons independently of activity. Using a novel computational model, we show that this simple growth rule produces neuron and network changes as observed in the visual cortex after focal retinal lesions. In the model, as in the cortex, the turnover of dendritic spines was increased strongest in the center of the lesion projection zone, while axonal boutons displayed a marked overshoot followed by pruning. Moreover, the decrease in external input was compensated for by the formation of new horizontal connections, which caused a retinotopic remapping. Homeostatic regulation may provide a unifying framework for understanding cortical reorganization, including network repair in degenerative diseases or following focal stroke. PMID:24130472

Moderate Cortical Cooling Eliminates Thalamocortical Silent States during Slow Oscillation.

PubMed

Sheroziya, Maxim; Timofeev, Igor

2015-09-23

Reduction in temperature depolarizes neurons by a partial closure of potassium channels but decreases the vesicle release probability within synapses. Compared with cooling, neuromodulators produce qualitatively similar effects on intrinsic neuronal properties and synapses in the cortex. We used this similarity of neuronal action in ketamine-xylazine-anesthetized mice and non-anesthetized mice to manipulate the thalamocortical activity. We recorded cortical electroencephalogram/local field potential (LFP) activity and intracellular activities from the somatosensory thalamus in control conditions, during cortical cooling and on rewarming. In the deeply anesthetized mice, moderate cortical cooling was characterized by reversible disruption of the thalamocortical slow-wave pattern rhythmicity and the appearance of fast LFP spikes, with frequencies ranging from 6 to 9 Hz. These LFP spikes were correlated with the rhythmic IPSP activities recorded within the thalamic ventral posterior medial neurons and with depolarizing events in the posterior nucleus neurons. Similar cooling of the cortex during light anesthesia rapidly and reversibly eliminated thalamocortical silent states and evoked thalamocortical persistent activity; conversely, mild heating increased thalamocortical slow-wave rhythmicity. In the non-anesthetized head-restrained mice, cooling also prevented the generation of thalamocortical silent states. We conclude that moderate cortical cooling might be used to manipulate slow-wave network activity and induce neuromodulator-independent transition to activated states. Significance statement: In this study, we demonstrate that moderate local cortical cooling of lightly anesthetized or naturally sleeping mice disrupts thalamocortical slow oscillation and induces the activated local field potential pattern. Mild heating has the opposite effect; it increases the rhythmicity of thalamocortical slow oscillation. Our results demonstrate that slow oscillation can be influenced by manipulations to the properties of cortical neurons without changes in neuromodulation. Copyright © 2015 the authors 0270-6474/15/3513006-14$15.00/0.

Mirror Neurons in a New World Monkey, Common Marmoset

PubMed Central

Suzuki, Wataru; Banno, Taku; Miyakawa, Naohisa; Abe, Hiroshi; Goda, Naokazu; Ichinohe, Noritaka

2015-01-01

Mirror neurons respond when executing a motor act and when observing others' similar act. So far, mirror neurons have been found only in macaques, humans, and songbirds. To investigate the degree of phylogenetic specialization of mirror neurons during the course of their evolution, we determined whether mirror neurons with similar properties to macaques occur in a New World monkey, the common marmoset (Callithrix jacchus). The ventral premotor cortex (PMv), where mirror neurons have been reported in macaques, is difficult to identify in marmosets, since no sulcal landmarks exist in the frontal cortex. We addressed this problem using “in vivo” connection imaging methods. That is, we first identified cells responsive to others' grasping action in a clear landmark, the superior temporal sulcus (STS), under anesthesia, and injected fluorescent tracers into the region. By fluorescence stereomicroscopy, we identified clusters of labeled cells in the ventrolateral frontal cortex, which were confirmed to be within the ventrolateral frontal cortex including PMv after sacrifice. We next implanted electrodes into the ventrolateral frontal cortex and STS and recorded single/multi-units under an awake condition. As a result, we found neurons in the ventrolateral frontal cortex with characteristic “mirror” properties quite similar to those in macaques. This finding suggests that mirror neurons occur in a common ancestor of New and Old World monkeys and its common properties are preserved during the course of primate evolution. PMID:26696817

Chromatic and Achromatic Spatial Resolution of Local Field Potentials in Awake Cortex.

PubMed

Jansen, Michael; Li, Xiaobing; Lashgari, Reza; Kremkow, Jens; Bereshpolova, Yulia; Swadlow, Harvey A; Zaidi, Qasim; Alonso, Jose-Manuel

2015-10-01

Local field potentials (LFPs) have become an important measure of neuronal population activity in the brain and could provide robust signals to guide the implant of visual cortical prosthesis in the future. However, it remains unclear whether LFPs can detect weak cortical responses (e.g., cortical responses to equiluminant color) and whether they have enough visual spatial resolution to distinguish different chromatic and achromatic stimulus patterns. By recording from awake behaving macaques in primary visual cortex, here we demonstrate that LFPs respond robustly to pure chromatic stimuli and exhibit ∼2.5 times lower spatial resolution for chromatic than achromatic stimulus patterns, a value that resembles the ratio of achromatic/chromatic resolution measured with psychophysical experiments in humans. We also show that, although the spatial resolution of LFP decays with visual eccentricity as is also the case for single neurons, LFPs have higher spatial resolution and show weaker response suppression to low spatial frequencies than spiking multiunit activity. These results indicate that LFP recordings are an excellent approach to measure spatial resolution from local populations of neurons in visual cortex including those responsive to color. © The Author 2014. Published by Oxford University Press.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism.

PubMed

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus.

Eyelid Opening with Trigeminal Proprioceptive Activation Regulates a Brainstem Arousal Mechanism

PubMed Central

Matsuo, Kiyoshi; Ban, Ryokuya; Hama, Yuki; Yuzuriha, Shunsuke

2015-01-01

Eyelid opening stretches mechanoreceptors in the supratarsal Müller muscle to activate the proprioceptive fiber supplied by the trigeminal mesencephalic nucleus. This proprioception induces reflex contractions of the slow-twitch fibers in the levator palpebrae superioris and frontalis muscles to sustain eyelid and eyebrow positions against gravity. The cell bodies of the trigeminal proprioceptive neurons in the mesencephalon potentially make gap-junctional connections with the locus coeruleus neurons. The locus coeruleus is implicated in arousal and autonomic function. Due to the relationship between arousal, ventromedial prefrontal cortex, and skin conductance, we assessed whether upgaze with trigeminal proprioceptive evocation activates sympathetically innervated sweat glands and the ventromedial prefrontal cortex. Specifically, we examined whether 60° upgaze induces palmar sweating and hemodynamic changes in the prefrontal cortex in 16 subjects. Sweating was monitored using a thumb-mounted perspiration meter, and prefrontal cortex activity was measured with 45-channel, functional near-infrared spectroscopy (fNIRS) and 2-channel NIRS at Fp1 and Fp2. In 16 subjects, palmar sweating was induced by upgaze and decreased in response to downgaze. Upgaze activated the ventromedial prefrontal cortex with an accumulation of integrated concentration changes in deoxyhemoglobin, oxyhemoglobin, and total hemoglobin levels in 12 subjects. Upgaze phasically and degree-dependently increased deoxyhemoglobin level at Fp1 and Fp2, whereas downgaze phasically decreased it in 16 subjects. Unilateral anesthetization of mechanoreceptors in the supratarsal Müller muscle used to significantly reduce trigeminal proprioceptive evocation ipsilaterally impaired the increased deoxyhemoglobin level by 60° upgaze at Fp1 or Fp2 in 6 subjects. We concluded that upgaze with strong trigeminal proprioceptive evocation was sufficient to phasically activate sympathetically innervated sweat glands and appeared to induce rapid oxygen consumption in the ventromedial prefrontal cortex and to rapidly produce deoxyhemoglobin to regulate physiological arousal. Thus, eyelid opening with trigeminal proprioceptive evocation may activate the ventromedial prefrontal cortex via the mesencephalic trigeminal nucleus and locus coeruleus. PMID:26244675

Pyruvate Administration Reduces Recurrent/Moderate Hypoglycemia-Induced Cortical Neuron Death in Diabetic Rats

PubMed Central

Choi, Bo Young; Kim, Jin Hee; Kim, Hyun Jung; Yoo, Jin Hyuk; Song, Hong Ki; Sohn, Min; Won, Seok Joon; Suh, Sang Won

2013-01-01

Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes patients. Moderate hypoglycemia is not life-threatening, but if experienced recurrently it may present several clinical complications. Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored. Pyruvate, however, can be metabolized in the absence of cytosolic NAD. We therefore hypothesized that pyruvate may be able to improve the outcome in diabetic rats subjected to insulin-induced R/M hypoglycemia by terminating hypoglycemia with glucose plus pyruvate, as compared with delivering just glucose alone. In an effort to mimic juvenile type 1 diabetes the experiments were conducted in one-month-old young rats that were rendered diabetic by streptozotocin (STZ, 50mg/kg, i.p.) injection. One week after STZ injection, rats were subjected to moderate hypoglycemia by insulin injection (10U/kg, i.p.) without anesthesia for five consecutive days. Pyruvate (500mg/kg) was given by intraperitoneal injection after each R/M hypoglycemia. Three hours after last R/M hypoglycemia, zinc accumulation was evaluated. Three days after R/M hypoglycemia, neuronal death, oxidative stress, microglial activation and GSH concentrations in the cerebral cortex were analyzed. Sparse neuronal death was observed in the cortex. Zinc accumulation, oxidative injury, microglial activation and GSH loss in the cortex after R/M hypoglycemia were all reduced by pyruvate injection. These findings suggest that when delivered alongside glucose, pyruvate may significantly improve the outcome after R/M hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation. PMID:24278448

Peripheral facial nerve lesions induce changes in the firing properties of primary motor cortex layer 5 pyramidal cells.

PubMed

Múnera, A; Cuestas, D M; Troncoso, J

2012-10-25

Facial nerve lesions elicit long-lasting changes in vibrissal primary motor cortex (M1) muscular representation in rodents. Reorganization of cortical representation has been attributed to potentiation of preexisting horizontal connections coming from neighboring muscle representation. However, changes in layer 5 pyramidal neuron activity induced by facial nerve lesion have not yet been explored. To do so, the effect of irreversible facial nerve injury on electrophysiological properties of layer 5 pyramidal neurons was characterized. Twenty-four adult male Wistar rats were randomly subjected to two experimental treatments: either surgical transection of mandibular and buccal branches of the facial nerve (n=18) or sham surgery (n=6). Unitary and population activity of vibrissal M1 layer 5 pyramidal neurons recorded in vivo under general anesthesia was compared between sham-operated and facial nerve-injured animals. Injured animals were allowed either one (n=6), three (n=6), or five (n=6) weeks recovery before recording in order to characterize the evolution of changes in electrophysiological activity. As compared to control, facial nerve-injured animals displayed the following sustained and significant changes in spontaneous activity: increased basal firing frequency, decreased spike-associated local field oscillation amplitude, and decreased spontaneous theta burst firing frequency. Significant changes in evoked-activity with whisker pad stimulation included: increased short latency population spike amplitude, decreased long latency population oscillations amplitude and frequency, and decreased peak frequency during evoked single-unit burst firing. Taken together, such changes demonstrate that peripheral facial nerve lesions induce robust and sustained changes of layer 5 pyramidal neurons in vibrissal motor cortex. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Adaptive Encoding of Outcome Prediction by Prefrontal Cortex Ensembles Supports Behavioral Flexibility.

PubMed

Del Arco, Alberto; Park, Junchol; Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

2017-08-30

The prefrontal cortex (PFC) is thought to play a critical role in behavioral flexibility by monitoring action-outcome contingencies. How PFC ensembles represent shifts in behavior in response to changes in these contingencies remains unclear. We recorded single-unit activity and local field potentials in the dorsomedial PFC (dmPFC) of male rats during a set-shifting task that required them to update their behavior, among competing options, in response to changes in action-outcome contingencies. As behavior was updated, a subset of PFC ensembles encoded the current trial outcome before the outcome was presented. This novel outcome-prediction encoding was absent in a control task, in which actions were rewarded pseudorandomly, indicating that PFC neurons are not merely providing an expectancy signal. In both control and set-shifting tasks, dmPFC neurons displayed postoutcome discrimination activity, indicating that these neurons also monitor whether a behavior is successful in generating rewards. Gamma-power oscillatory activity increased before the outcome in both tasks but did not differentiate between expected outcomes, suggesting that this measure is not related to set-shifting behavior but reflects expectation of an outcome after action execution. These results demonstrate that PFC neurons support flexible rule-based action selection by predicting outcomes that follow a particular action. SIGNIFICANCE STATEMENT Tracking action-outcome contingencies and modifying behavior when those contingencies change is critical to behavioral flexibility. We find that ensembles of dorsomedial prefrontal cortex neurons differentiate between expected outcomes when action-outcome contingencies change. This predictive mode of signaling may be used to promote a new response strategy at the service of behavioral flexibility. Copyright © 2017 the authors 0270-6474/17/378363-11$15.00/0.

[Intranasal epitalon infusion modulates neuronal activity in the rat neocortex].

PubMed

Sibarov, D A; Vol'nova, A B; Frolov, D S; Nosdrachev, A D

2006-08-01

Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of pineal peptide extract, have been studied. The intranasal infusions: a noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier, was used. The aim of the study is to estimate epitalon action on rat motor cortex spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg). Extracellular unit recording was made using glass microelectrodes (1-2 MOhm). After recording of spontaneous activity (10-15 min), epitalon intranasal infusion (2 ng) was followed by 30-minute recording. Within a few minutes after the infusion, significant activation of neural activity was observed (2-2.5-fold higher frequency of neuronal spikes). Complex response consisting of several phases was identified in some recordings. The spikes frequency growth during 5 to 7 min (first phase) after the infusion was followed by the second (11-12 min) and the third (17-18 min) phases. An increase of neuronal spontaneous activity was conditioned by the higher frequency of already active units and by the involvement of previously silent cells. At least the first phase of epitalon action can be explained by direct action of the peptide on the cells of the motor cortex.

New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function

PubMed Central

Jeon, Won Je; Sumiyoshi, Tomiki; Kurachi, Masayoshi

2015-01-01

Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of GABA neural function. On the other hand, T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as cognitive dysfunction in animal model of schizophrenia. In conclusion, a pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and T-817MA is expected to prevent the onset and/or progression of schizophrenia. PMID:26630957

New Pharmacotherapy Targeting Cognitive Dysfunction of Schizophrenia via Modulation of GABA Neuronal Function.

PubMed

Uehara, Takashi; Sumiyoshi, Tomiki; Kurachi, Masayoshi

2015-01-01

Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Cognitive impairment is a core symptom in patients with the illness, and has been suggested a major predictor of functional outcomes. Reduction of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons has been associated with the pathophysiology of schizophrenia, in view of the link between the abnormality of GABA neurons and cognitive impairments of the disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by low activity of glutamatergic projections and PV-positive GABA interneurons in the prefrontal cortex resulted in sustained neural firing and gamma oscillation, leading to impaired cognitive function. Therefore, it is important to develop novel pharmacotherapy targeting GABA neurons and their activities. Clinical evidence suggests serotonin (5-HT) 1A receptor agonist improves cognitive disturbances of schizophrenia, consistent with results from preclinical studies, through mechanism that corrects E-I imbalance via the suppression of GABA neural function. On the other hand, T-817MA, a novel neurotrophic agent, ameliorated loss of PV-positive GABA neurons in the medial prefrontal cortex and reduction of gamma-band activity, as well as cognitive dysfunction in animal model of schizophrenia. In conclusion, a pharmacotherapy to alleviate abnormalities in GABA neurons through 5-HT1A agonists and T-817MA is expected to prevent the onset and/or progression of schizophrenia.

Single-Cell Analysis of Experience-Dependent Transcriptomic States in Mouse Visual Cortex

PubMed Central

Hrvatin, Sinisa; Hochbaum, Daniel R.; Nagy, M. Aurel; Cicconet, Marcelo; Robertson, Keiramarie; Cheadle, Lucas; Zilionis, Rapolas; Ratner, Alex; Borges-Monroy, Rebeca; Klein, Allon M.; Sabatini, Bernardo L.; Greenberg, Michael E.

2017-01-01

Activity-dependent transcriptional responses shape cortical function. However, we lack a comprehensive understanding of the diversity of these responses across the full range of cortical cell types, and how these changes contribute to neuronal plasticity and disease. Here we applied high-throughput single-cell RNA-sequencing to investigate the breadth of transcriptional changes that occur across cell types in mouse visual cortex following exposure to light. We identified significant and divergent transcriptional responses to stimulation in each of the 30 cell types characterized, revealing 611 stimulus-responsive genes. Excitatory pyramidal neurons exhibit inter- and intra-laminar heterogeneity in the induction of stimulus responsive genes. Non-neuronal cells demonstrated clear transcriptional responses that may regulate experience-dependent changes in neurovascular coupling and myelination. Together, these results reveal the dynamic landscape of stimulus-dependent transcriptional changes that occur across cell types in visual cortex, which are likely critical for cortical function and may be sites of de-regulation in developmental brain disorders. PMID:29230054

Poisson-Like Spiking in Circuits with Probabilistic Synapses

PubMed Central

Moreno-Bote, Rubén

2014-01-01

Neuronal activity in cortex is variable both spontaneously and during stimulation, and it has the remarkable property that it is Poisson-like over broad ranges of firing rates covering from virtually zero to hundreds of spikes per second. The mechanisms underlying cortical-like spiking variability over such a broad continuum of rates are currently unknown. We show that neuronal networks endowed with probabilistic synaptic transmission, a well-documented source of variability in cortex, robustly generate Poisson-like variability over several orders of magnitude in their firing rate without fine-tuning of the network parameters. Other sources of variability, such as random synaptic delays or spike generation jittering, do not lead to Poisson-like variability at high rates because they cannot be sufficiently amplified by recurrent neuronal networks. We also show that probabilistic synapses predict Fano factor constancy of synaptic conductances. Our results suggest that synaptic noise is a robust and sufficient mechanism for the type of variability found in cortex. PMID:25032705

High-alpha band synchronization across frontal, parietal and visual cortex mediates behavioral and neuronal effects of visuospatial attention.

PubMed

Lobier, Muriel; Palva, J Matias; Palva, Satu

2018-01-15

Visuospatial attention prioritizes processing of attended visual stimuli. It is characterized by lateralized alpha-band (8-14 Hz) amplitude suppression in visual cortex and increased neuronal activity in a network of frontal and parietal areas. It has remained unknown what mechanisms coordinate neuronal processing among frontoparietal network and visual cortices and implement the attention-related modulations of alpha-band amplitudes and behavior. We investigated whether large-scale network synchronization could be such a mechanism. We recorded human cortical activity with magnetoencephalography (MEG) during a visuospatial attention task. We then identified the frequencies and anatomical networks of inter-areal phase synchronization from source localized MEG data. We found that visuospatial attention is associated with robust and sustained long-range synchronization of cortical oscillations exclusively in the high-alpha (10-14 Hz) frequency band. This synchronization connected frontal, parietal and visual regions and was observed concurrently with amplitude suppression of low-alpha (6-9 Hz) band oscillations in visual cortex. Furthermore, stronger high-alpha phase synchronization was associated with decreased reaction times to attended stimuli and larger suppression of alpha-band amplitudes. These results thus show that high-alpha band phase synchronization is functionally significant and could coordinate the neuronal communication underlying the implementation of visuospatial attention. Copyright © 2017 Elsevier Inc. All rights reserved.

CREB binding protein is required for both short-term and long-term memory formation.

PubMed

Chen, Guiquan; Zou, Xiaoyan; Watanabe, Hirotaka; van Deursen, Jan M; Shen, Jie

2010-09-29

CREB binding protein (CBP) is a transcriptional coactivator with histone acetyltransferase activity. Our prior study suggested that CBP might be a key target of presenilins in the regulation of memory formation and neuronal survival. To elucidate the role of CBP in the adult brain, we generated conditional knock-out (cKO) mice in which CBP is completely inactivated in excitatory neurons of the postnatal forebrain. Histological analysis revealed normal neuronal morphology and absence of age-dependent neuronal degeneration in the CBP cKO cerebral cortex. CBP cKO mice exhibited robust impairment in the formation of spatial, associative, and object-recognition memory. In addition to impaired long-term memory, CBP cKO mice also displayed deficits in short-term associative and object-recognition memory. Administration of a histone deacetylase inhibitor, trichostatin A, rescued the reduction of acetylated histones in the CBP cKO cortex but failed to rescue either short- or long-term memory deficits, suggesting that the memory impairment may not be caused by general reduction of histone acetyltransferase activity in CBP cKO mice. Further microarray and Western analysis showed decreased expression of calcium-calmodulin-dependent kinase isoforms and NMDA and AMPA receptor subunits in the cerebral cortex of CBP cKO mice. Collectively, these findings suggest a crucial role for CBP in the formation of both short- and long-term memory.

Variability and Correlations in Primary Visual Cortical Neurons Driven by Fixational Eye Movements

PubMed Central

McFarland, James M.; Cumming, Bruce G.

2016-01-01

The ability to distinguish between elements of a sensory neuron's activity that are stimulus independent versus driven by the stimulus is critical for addressing many questions in systems neuroscience. This is typically accomplished by measuring neural responses to repeated presentations of identical stimuli and identifying the trial-variable components of the response as noise. In awake primates, however, small “fixational” eye movements (FEMs) introduce uncontrolled trial-to-trial differences in the visual stimulus itself, potentially confounding this distinction. Here, we describe novel analytical methods that directly quantify the stimulus-driven and stimulus-independent components of visual neuron responses in the presence of FEMs. We apply this approach, combined with precise model-based eye tracking, to recordings from primary visual cortex (V1), finding that standard approaches that ignore FEMs typically miss more than half of the stimulus-driven neural response variance, creating substantial biases in measures of response reliability. We show that these effects are likely not isolated to the particular experimental conditions used here, such as the choice of visual stimulus or spike measurement time window, and thus will be a more general problem for V1 recordings in awake primates. We also demonstrate that measurements of the stimulus-driven and stimulus-independent correlations among pairs of V1 neurons can be greatly biased by FEMs. These results thus illustrate the potentially dramatic impact of FEMs on measures of signal and noise in visual neuron activity and also demonstrate a novel approach for controlling for these eye-movement-induced effects. SIGNIFICANCE STATEMENT Distinguishing between the signal and noise in a sensory neuron's activity is typically accomplished by measuring neural responses to repeated presentations of an identical stimulus. For recordings from the visual cortex of awake animals, small “fixational” eye movements (FEMs) inevitably introduce trial-to-trial variability in the visual stimulus, potentially confounding such measures. Here, we show that FEMs often have a dramatic impact on several important measures of response variability for neurons in primary visual cortex. We also present an analytical approach for quantifying signal and noise in visual neuron activity in the presence of FEMs. These results thus highlight the importance of controlling for FEMs in studies of visual neuron function, and demonstrate novel methods for doing so. PMID:27277801

The effects of sesquiterpenes-rich extract of Alpinia oxyphylla Miq. on amyloid-β-induced cognitive impairment and neuronal abnormalities in the cortex and hippocampus of mice.

PubMed

Shi, Shao-Huai; Zhao, Xu; Liu, Bing; Li, Huan; Liu, Ai-Jing; Wu, Bo; Bi, Kai-Shun; Jia, Ying

2014-01-01

As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Aβ(1-42) and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-β (Aβ), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions.

The Effects of Sesquiterpenes-Rich Extract of Alpinia oxyphylla Miq. on Amyloid-β-Induced Cognitive Impairment and Neuronal Abnormalities in the Cortex and Hippocampus of Mice

PubMed Central

Shi, Shao-Huai; Zhao, Xu; Liu, Bing; Li, Huan; Liu, Ai-Jing; Wu, Bo; Bi, Kai-Shun

2014-01-01

As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Aβ 1−42 and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-β (Aβ), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions. PMID:25180067

Emergence of Adaptive Computation by Single Neurons in the Developing Cortex

PubMed Central

Famulare, Michael; Gjorgjieva, Julijana; Moody, William J.

2013-01-01

Adaptation is a fundamental computational motif in neural processing. To maintain stable perception in the face of rapidly shifting input, neural systems must extract relevant information from background fluctuations under many different contexts. Many neural systems are able to adjust their input–output properties such that an input's ability to trigger a response depends on the size of that input relative to its local statistical context. This “gain-scaling” strategy has been shown to be an efficient coding strategy. We report here that this property emerges during early development as an intrinsic property of single neurons in mouse sensorimotor cortex, coinciding with the disappearance of spontaneous waves of network activity, and can be modulated by changing the balance of spike-generating currents. Simultaneously, developing neurons move toward a common intrinsic operating point and a stable ratio of spike-generating currents. This developmental trajectory occurs in the absence of sensory input or spontaneous network activity. Through a combination of electrophysiology and modeling, we demonstrate that developing cortical neurons develop the ability to perform nearly perfect gain scaling by virtue of the maturing spike-generating currents alone. We use reduced single neuron models to identify the conditions for this property to hold. PMID:23884925

Neuronal ensemble control of prosthetic devices by a human with tetraplegia

NASA Astrophysics Data System (ADS)

Hochberg, Leigh R.; Serruya, Mijail D.; Friehs, Gerhard M.; Mukand, Jon A.; Saleh, Maryam; Caplan, Abraham H.; Branner, Almut; Chen, David; Penn, Richard D.; Donoghue, John P.

2006-07-01

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a `neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

PubMed

Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

2017-06-15

TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement of the ventral premotor cortex in controlling image motion of the hand during performance of a target-capturing task.

PubMed

Ochiai, Tetsuji; Mushiake, Hajime; Tanji, Jun

2005-07-01

The ventral premotor cortex (PMv) has been implicated in the visual guidance of movement. To examine whether neuronal activity in the PMv is involved in controlling the direction of motion of a visual image of the hand or the actual movement of the hand, we trained a monkey to capture a target that was presented on a video display using the same side of its hand as was displayed on the video display. We found that PMv neurons predominantly exhibited premovement activity that reflected the image motion to be controlled, rather than the physical motion of the hand. We also found that the activity of half of such direction-selective PMv neurons depended on which side (left versus right) of the video image of the hand was used to capture the target. Furthermore, this selectivity for a portion of the hand was not affected by changing the starting position of the hand movement. These findings suggest that PMv neurons play a crucial role in determining which part of the body moves in which direction, at least under conditions in which a visual image of a limb is used to guide limb movements.

Processing of Intraoral Olfactory and Gustatory Signals in the Gustatory Cortex of Awake Rats

PubMed Central

Fontanini, Alfredo

2017-01-01

The integration of gustatory and olfactory information is essential to the perception of flavor. Human neuroimaging experiments have pointed to the gustatory cortex (GC) as one of the areas involved in mediating flavor perception. Although GC's involvement in encoding the chemical identity and hedonic value of taste stimuli is well studied, it is unknown how single GC neurons process olfactory stimuli emanating from the mouth. In this study, we relied on multielectrode recordings to investigate how single GC neurons respond to intraorally delivered tastants and tasteless odorants dissolved in water and whether/how these two modalities converge in the same neurons. We found that GC neurons could either be unimodal, responding exclusively to taste (taste-only) or odor (odor-only), or bimodal, responding to both gustatory and olfactory stimuli. Odor responses were confirmed to result from retronasal olfaction: monitoring respiration revealed that exhalation preceded odor-evoked activity and reversible inactivation of olfactory receptors in the nasal epithelium significantly reduced responses to intraoral odorants but not to tastants. Analysis of bimodal neurons revealed that they encode palatability significantly better than the unimodal taste-only group. Bimodal neurons exhibited similar responses to palatable tastants and odorants dissolved in water. This result suggested that odorized water could be palatable. This interpretation was further supported with a brief access task, where rats avoided consuming aversive taste stimuli and consumed the palatable tastants and dissolved odorants. These results demonstrate the convergence of the chemosensory components of flavor onto single GC neurons and provide evidence for the integration of flavor with palatability coding. SIGNIFICANCE STATEMENT Food perception and choice depend upon the concurrent processing of olfactory and gustatory signals from the mouth. The primary gustatory cortex has been proposed to integrate chemosensory stimuli; however, no study has examined the single-unit responses to intraoral odorant presentation. Here we found that neurons in gustatory cortex can respond either exclusively to tastants, exclusively to odorants, or to both (bimodal). Several differences exist between these groups' responses; notably, bimodal neurons code palatability significantly better than unimodal neurons. This group of neurons might represent a substrate for how odorants gain the quality of tastants. PMID:28077705

d-LSD-induced c-Fos expression occurs in a population of oligodendrocytes in rat prefrontal cortex.

PubMed

Reissig, Chad J; Rabin, Richard A; Winter, Jerrold C; Dlugos, Cynthia A

2008-03-31

Induction of mRNA or protein for immediate-early genes, such as c-fos, is used to identify brain areas, specific cell types, and neuronal circuits that become activated in response to various stimuli including psychoactive drugs. The objective of the present study was to identify the cell types in the prefrontal cortex in which lysergic acid diethylamide (d-LSD) induces c-Fos expression. Systemic administration of d-LSD resulted in a dose-dependent increase in c-Fos immunoreactivity. Although c-Fos-positive cells were found in all cortical layers, they were most numerous in layers III, IV, and V. d-LSD-induced c-Fos immunoreactivity was found in cells co-labeled with anti-neuron-specific enolase or anti-oligodendrocyte Oligo1. The Oligo1-labeled cells had small, round bodies and nuclear diameters characteristic of oligodendrocytes. Studies using confocal microscopy confirmed colocalization of c-Fos-labeled nuclei in NeuN-labeled neurons. Astrocytes and microglia labeled with glial fibrillary acidic protein antibody and OX-42 antibody, respectively, did not display LSD-induced c-Fos expression. Pyramidal neurons labeled with anti-neurofilament antibody also did not show induction of c-Fos immunoreactivity after systemic d-LSD administration. The present study demonstrates that d-LSD induced expression of c-Fos in the prefrontal cortex occurs in subpopulations of neurons and in oligodendrocytes, but not in pyramidal neurons, astrocytes, and microglia.

Local and Global Correlations between Neurons in the Middle Temporal Area of Primate Visual Cortex.

PubMed

Solomon, Selina S; Chen, Spencer C; Morley, John W; Solomon, Samuel G

2015-09-01

In humans and other primates, the analysis of visual motion includes populations of neurons in the middle-temporal (MT) area of visual cortex. Motion analysis will be constrained by the structure of neural correlations in these populations. Here, we use multi-electrode arrays to measure correlations in anesthetized marmoset, a New World monkey where area MT lies exposed on the cortical surface. We measured correlations in the spike count between pairs of neurons and within populations of neurons, for moving dot fields and moving gratings. Correlations were weaker in area MT than in area V1. The magnitude of correlations in area MT diminished with distance between receptive fields, and difference in preferred direction. Correlations during presentation of moving gratings were stronger than those during presentation of moving dot fields, extended further across cortex, and were less dependent on the functional properties of neurons. Analysis of the timescales of correlation suggests presence of 2 mechanisms. A local mechanism, associated with near-synchronous spiking activity, is strongest in nearby neurons with similar direction preference and is independent of visual stimulus. A global mechanism, operating over larger spatial scales and longer timescales, is independent of direction preference and is modulated by the type of visual stimulus presented. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cellular scaling rules for the brain of afrotherians

PubMed Central

Neves, Kleber; Ferreira, Fernanda M.; Tovar-Moll, Fernanda; Gravett, Nadine; Bennett, Nigel C.; Kaswera, Consolate; Gilissen, Emmanuel; Manger, Paul R.; Herculano-Houzel, Suzana

2014-01-01

Quantitative analysis of the cellular composition of rodent, primate and eulipotyphlan brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in evolution in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of afrotherians, believed to be the first clade to radiate from the common eutherian ancestor. We find that afrotherians share non-neuronal scaling rules with rodents, primates and eulipotyphlans, as well as the coordinated scaling of numbers of neurons in the cerebral cortex and cerebellum. Afrotherians share with rodents and eulipotyphlans, but not with primates, the scaling of number of neurons in the cortex and in the cerebellum as a function of the number of neurons in the rest of the brain. Afrotheria also share with rodents and eulipotyphlans the neuronal scaling rules that apply to the cerebral cortex. Afrotherians share with rodents, but not with eulipotyphlans nor primates, the neuronal scaling rules that apply to the cerebellum. Importantly, the scaling of the folding index of the cerebral cortex with the number of neurons in the cerebral cortex is not shared by either afrotherians, rodents, or primates. The sharing of some neuronal scaling rules between afrotherians and rodents, and of some additional features with eulipotyphlans and primates, raise the interesting possibility that these shared characteristics applied to the common eutherian ancestor. In turn, the clade-specific characteristics that relate to the distribution of neurons along the surface of the cerebral cortex and to its degree of gyrification suggest that these characteristics compose an evolutionarily plastic suite of features that may have defined and distinguished mammalian groups in evolution. PMID:24596544

Modeling task-specific neuronal ensembles improves decoding of grasp

NASA Astrophysics Data System (ADS)

Smith, Ryan J.; Soares, Alcimar B.; Rouse, Adam G.; Schieber, Marc H.; Thakor, Nitish V.

2018-06-01

Objective. Dexterous movement involves the activation and coordination of networks of neuronal populations across multiple cortical regions. Attempts to model firing of individual neurons commonly treat the firing rate as directly modulating with motor behavior. However, motor behavior may additionally be associated with modulations in the activity and functional connectivity of neurons in a broader ensemble. Accounting for variations in neural ensemble connectivity may provide additional information about the behavior being performed. Approach. In this study, we examined neural ensemble activity in primary motor cortex (M1) and premotor cortex (PM) of two male rhesus monkeys during performance of a center-out reach, grasp and manipulate task. We constructed point process encoding models of neuronal firing that incorporated task-specific variations in the baseline firing rate as well as variations in functional connectivity with the neural ensemble. Models were evaluated both in terms of their encoding capabilities and their ability to properly classify the grasp being performed. Main results. Task-specific ensemble models correctly predicted the performed grasp with over 95% accuracy and were shown to outperform models of neuronal activity that assume only a variable baseline firing rate. Task-specific ensemble models exhibited superior decoding performance in 82% of units in both monkeys (p  <  0.01). Inclusion of ensemble activity also broadly improved the ability of models to describe observed spiking. Encoding performance of task-specific ensemble models, measured by spike timing predictability, improved upon baseline models in 62% of units. Significance. These results suggest that additional discriminative information about motor behavior found in the variations in functional connectivity of neuronal ensembles located in motor-related cortical regions is relevant to decode complex tasks such as grasping objects, and may serve the basis for more reliable and accurate neural prosthesis.

Systemic administration of WIN 55,212-2 increases norepinephrine release in the rat frontal cortex.

PubMed

Oropeza, V C; Page, M E; Van Bockstaele, E J

2005-06-07

Cannabinoid agonists modulate a variety of behavioral functions by activating cannabinoid receptors that are widely distributed throughout the central nervous system. In the present study, norepinephrine efflux was assessed in the frontal cortex of rats that received a systemic administration of the cannabinoid agonist, WIN 55,212-2. The synthetic cannabinoid agonist dose-dependently increased the release of norepinephrine in this brain region. Pretreatment with the cannabinoid receptor antagonist, SR 141716A, blocked the increase in norepinephrine release. To identify sites of cellular activation, immunocytochemical detection of c-Fos was combined with detection of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), in the brainstem nucleus locus coeruleus (LC), a region that is the sole source of norepinephrine to the frontal cortex. Systemic administration of WIN 55,212-2 significantly increased the number of c-Fos immunoreactive cells within TH-containing neurons in the LC compared to vehicle-treated rats. Pretreatment with SR 141716A inhibited the WIN 55,212-2 induced c-Fos expression, while the antagonist alone did not affect c-Fos expression. Taken together, these data indicate that systemically administered cannabinoid agonists stimulate norepinephrine release in the frontal cortex by activating noradrenergic neurons in the coeruleo-frontal cortex pathway. These effects may partially underlie changes in attention, arousal and anxiety observed following exposure to cannabis-based drugs.

Gender differences in human single neuron responses to male emotional faces

PubMed Central

Newhoff, Morgan; Treiman, David M.; Smith, Kris A.; Steinmetz, Peter N.

2015-01-01

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p < 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala. PMID:26441597

Redundant information encoding in primary motor cortex during natural and prosthetic motor control.

PubMed

So, Kelvin; Ganguly, Karunesh; Jimenez, Jessica; Gastpar, Michael C; Carmena, Jose M

2012-06-01

Redundant encoding of information facilitates reliable distributed information processing. To explore this hypothesis in the motor system, we applied concepts from information theory to quantify the redundancy of movement-related information encoded in the macaque primary motor cortex (M1) during natural and neuroprosthetic control. Two macaque monkeys were trained to perform a delay center-out reaching task controlling a computer cursor under natural arm movement (manual control, 'MC'), and using a brain-machine interface (BMI) via volitional control of neural ensemble activity (brain control, 'BC'). During MC, we found neurons in contralateral M1 to contain higher and more redundant information about target direction than ipsilateral M1 neurons, consistent with the laterality of movement control. During BC, we found that the M1 neurons directly incorporated into the BMI ('direct' neurons) contained the highest and most redundant target information compared to neurons that were not incorporated into the BMI ('indirect' neurons). This effect was even more significant when comparing to M1 neurons of the opposite hemisphere. Interestingly, when we retrained the BMI to use ipsilateral M1 activity, we found that these neurons were more redundant and contained higher information than contralateral M1 neurons, even though ensembles from this hemisphere were previously less redundant during natural arm movement. These results indicate that ensembles most associated to movement contain highest redundancy and information encoding, which suggests a role for redundancy in proficient natural and prosthetic motor control.

Spike synchrony reveals emergence of proto-objects in visual cortex.

PubMed

Martin, Anne B; von der Heydt, Rüdiger

2015-04-29

Neurons at early stages of the visual cortex signal elemental features, such as pieces of contour, but how these signals are organized into perceptual objects is unclear. Theories have proposed that spiking synchrony between these neurons encodes how features are grouped (binding-by-synchrony), but recent studies did not find the predicted increase in synchrony with binding. Here we propose that features are grouped to "proto-objects" by intrinsic feedback circuits that enhance the responses of the participating feature neurons. This hypothesis predicts synchrony exclusively between feature neurons that receive feedback from the same grouping circuit. We recorded from neurons in macaque visual cortex and used border-ownership selectivity, an intrinsic property of the neurons, to infer whether or not two neurons are part of the same grouping circuit. We found that binding produced synchrony between same-circuit neurons, but not between other pairs of neurons, as predicted by the grouping hypothesis. In a selective attention task, synchrony emerged with ignored as well as attended objects, and higher synchrony was associated with faster behavioral responses, as would be expected from early grouping mechanisms that provide the structure for object-based processing. Thus, synchrony could be produced by automatic activation of intrinsic grouping circuits. However, the binding-related elevation of synchrony was weak compared with its random fluctuations, arguing against synchrony as a code for binding. In contrast, feedback grouping circuits encode binding by modulating the response strength of related feature neurons. Thus, our results suggest a novel coding mechanism that might underlie the proto-objects of perception. Copyright © 2015 the authors 0270-6474/15/356860-11$15.00/0.

Natural asynchronies in audiovisual communication signals regulate neuronal multisensory interactions in voice-sensitive cortex

PubMed Central

Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K.; Petkov, Christopher I.

2015-01-01

When social animals communicate, the onset of informative content in one modality varies considerably relative to the other, such as when visual orofacial movements precede a vocalization. These naturally occurring asynchronies do not disrupt intelligibility or perceptual coherence. However, they occur on time scales where they likely affect integrative neuronal activity in ways that have remained unclear, especially for hierarchically downstream regions in which neurons exhibit temporally imprecise but highly selective responses to communication signals. To address this, we exploited naturally occurring face- and voice-onset asynchronies in primate vocalizations. Using these as stimuli we recorded cortical oscillations and neuronal spiking responses from functional MRI (fMRI)-localized voice-sensitive cortex in the anterior temporal lobe of macaques. We show that the onset of the visual face stimulus resets the phase of low-frequency oscillations, and that the face–voice asynchrony affects the prominence of two key types of neuronal multisensory responses: enhancement or suppression. Our findings show a three-way association between temporal delays in audiovisual communication signals, phase-resetting of ongoing oscillations, and the sign of multisensory responses. The results reveal how natural onset asynchronies in cross-sensory inputs regulate network oscillations and neuronal excitability in the voice-sensitive cortex of macaques, a suggested animal model for human voice areas. These findings also advance predictions on the impact of multisensory input on neuronal processes in face areas and other brain regions. PMID:25535356

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

PubMed Central

Marrone, Maria Cristina; Morabito, Annunziato; Giustizieri, Michela; Chiurchiù, Valerio; Leuti, Alessandro; Mattioli, Marzia; Marinelli, Sara; Riganti, Loredana; Lombardi, Marta; Murana, Emanuele; Totaro, Antonio; Piomelli, Daniele; Ragozzino, Davide; Oddi, Sergio; Maccarrone, Mauro; Verderio, Claudia; Marinelli, Silvia

2017-01-01

The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication. PMID:28489079

EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism.

PubMed

Puzzo, Ignazio; Cooper, Nicholas R; Vetter, Petra; Russo, Riccardo

2010-06-25

The human mirror neuron system (hMNS) is believed to provide a basic mechanism for social cognition. Event-related desynchronization (ERD) in alpha (8-12Hz) and low beta band (12-20Hz) over sensori-motor cortex has been suggested to index mirror neurons' activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation-execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth. Copyright 2010 Elsevier B.V. All rights reserved.

Transcranial Direct Current Stimulation Modulates Neuronal Networks in Attention Deficit Hyperactivity Disorder.

PubMed

Sotnikova, Anna; Soff, Cornelia; Tagliazucchi, Enzo; Becker, Katja; Siniatchkin, Michael

2017-09-01

Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been repeatedly shown to improve working memory (WM). Since patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in WM, the modulation of prefrontal activity with tDCS in ADHD patients may increase their WM performance as well as improve the activation and connectivity of the WM network. In the present study, this hypothesis was tested using a double-blind sham-controlled experimental design. After randomization, sixteen adolescents with ADHD underwent either anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC, 1 mA, 20 min) or sham stimulation with simultaneous fMRI during n-back WM task. Both in one-back and two-back conditions, tDCS led to a greater activation (compared with sham stimulation) of the left DLPFC (under the electrode), left premotor cortex, left supplementary motor cortex, and precuneus. The effects of tDCS were long-lasting and influenced resting state functional connectivity even 20 min after the stimulation, with patterns of strengthened DLPFC connectivity after tDCS outlining the WM network. In summary, anodal tDCS caused increased neuronal activation and connectivity, not only in the brain area under the stimulating electrode (i.e. left DLPFC) but also in other, more remote brain regions. Because of moderate behavioral effects of tDCS, the significance of this technique for ADHD treatment has to be investigated in further studies.

Region specific regulation of glutamic acid decarboxylase mRNA expression by dopamine neurons in rat brain.

PubMed

Lindefors, N; Brene, S; Herrera-Marschitz, M; Persson, H

1989-01-01

In situ hybridization histochemistry and RNA blots were used to study the expression of glutamic acid decarboxylase (GAD) mRNA in rats with or without a unilateral lesion of midbrain dopamine neurons. Two populations of GAD mRNA positive neurons were found in the intact caudate-putamen, substantia nigra and fronto-parietal cortex. In caudate-putamen, only one out of ten of the GAD mRNA positive neurons expressed high levels, while in substantia nigra every second of the positive neurons expressed high levels of GAD mRNA. Relatively few, but intensively labelled neurons were found in the intact fronto-parietal cerebral cortex. In addition, one out of six of the GAD mRNA positive neurons in the fronto-parietal cortex showed a low labeling. On the ipsilateral side, the forebrain dopamine deafferentation induced an increase in the number of neurons expressing high levels of GAD mRNA in caudate-putamen, and a decrease in fronto-parietal cortex. A smaller decrease was also seen in substantia nigra. However, the total number of GAD mRNA positive neurons were not significantly changed in any of these brain regions. The changes in the levels of GAD mRNA after the dopamine lesion were confirmed by RNA blot analysis. Hence, midbrain dopamine neurons appear to control neuronal expression of GAD mRNA by a tonic down-regulation in a fraction of GAD mRNA positive neurons in caudate-putamen, and a tonic up-regulation in a fraction of GAD mRNA positive neurons in fronto-parietal cortex and substantia nigra.

Cross-modality Sharpening of Visual Cortical Processing through Layer 1-Mediated Inhibition and Disinhibition

PubMed Central

Ibrahim, Leena A.; Mesik, Lukas; Ji, Xu-ying; Fang, Qi; Li, Hai-fu; Li, Ya-tang; Zingg, Brian; Zhang, Li I.; Tao, Huizhong Whit

2016-01-01

Summary Cross-modality interaction in sensory perception is advantageous for animals’ survival. How cortical sensory processing is cross-modally modulated and what are the underlying neural circuits remain poorly understood. In mouse primary visual cortex (V1), we discovered that orientation selectivity of layer (L)2/3 but not L4 excitatory neurons was sharpened in the presence of sound or optogenetic activation of projections from primary auditory cortex (A1) to V1. The effect was manifested by decreased average visual responses yet increased responses at the preferred orientation. It was more pronounced at lower visual contrast, and was diminished by suppressing L1 activity. L1 neurons were strongly innervated by A1-V1 axons and excited by sound, while visual responses of L2/3 vasoactive intestinal peptide (VIP) neurons were suppressed by sound, both preferentially at the cell's preferred orientation. These results suggest that the cross-modality modulation is achieved primarily through L1 neuron and L2/3 VIP-cell mediated inhibitory and disinhibitory circuits. PMID:26898778

OVEREXPRESSION OF SERUM RESPONSE FACTOR IN ASTROCYTES IMPROVES NEURONAL PLASTICITY IN A MODEL OF EARLY ALCOHOL EXPOSURE

PubMed Central

PAUL, ARCO P.; MEDINA, ALEXANDRE E.

2012-01-01

Neuronal plasticity deficits underlie many of the cognitive problems seen in Fetal Alcohol Spectrum Disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF−) or control GFP. After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF− or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD. PMID:22742904

Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex

PubMed Central

Pilkiw, Maryna; Insel, Nathan; Cui, Younghua; Finney, Caitlin; Morrissey, Mark D; Takehara-Nishiuchi, Kaori

2017-01-01

The lateral entorhinal cortex (LEC) is thought to bind sensory events with the environment where they took place. To compare the relative influence of transient events and temporally stable environmental stimuli on the firing of LEC cells, we recorded neuron spiking patterns in the region during blocks of a trace eyeblink conditioning paradigm performed in two environments and with different conditioning stimuli. Firing rates of some neurons were phasically selective for conditioned stimuli in a way that depended on which room the rat was in; nearly all neurons were tonically selective for environments in a way that depended on which stimuli had been presented in those environments. As rats moved from one environment to another, tonic neuron ensemble activity exhibited prospective information about the conditioned stimulus associated with the environment. Thus, the LEC formed phasic and tonic codes for event-environment associations, thereby accurately differentiating multiple experiences with overlapping features. DOI: http://dx.doi.org/10.7554/eLife.28611.001 PMID:28682237

Electrolytic Lesions of the Medial Prefrontal Cortex Do Not Interfere with Long-Term Memory of Extinction of Conditioned Fear

ERIC Educational Resources Information Center

Garcia, Rene; Chang, Chun-hui; Maren, Stephen

2006-01-01

Lesion studies indicate that rats without the medial prefrontal cortex (mPFC) have difficulty recalling fear extinction acquired the previous day. Several electrophysiological studies have also supported this observation by demonstrating that extinction-related increases in neuronal activity in the mPFC participate in expression of fear…

Astrocyte and Neuronal Plasticity in the Somatosensory System

PubMed Central

Sims, Robert E.; Butcher, John B.; Parri, H. Rheinallt; Glazewski, Stanislaw

2015-01-01

Changing the whisker complement on a rodent's snout can lead to two forms of experience-dependent plasticity (EDP) in the neurons of the barrel cortex, where whiskers are somatotopically represented. One form, termed coding plasticity, concerns changes in synaptic transmission and connectivity between neurons. This is thought to underlie learning and memory processes and so adaptation to a changing environment. The second, called homeostatic plasticity, serves to maintain a restricted dynamic range of neuronal activity thus preventing its saturation or total downregulation. Current explanatory models of cortical EDP are almost exclusively neurocentric. However, in recent years, increasing evidence has emerged on the role of astrocytes in brain function, including plasticity. Indeed, astrocytes appear as necessary partners of neurons at the core of the mechanisms of coding and homeostatic plasticity recorded in neurons. In addition to neuronal plasticity, several different forms of astrocytic plasticity have recently been discovered. They extend from changes in receptor expression and dynamic changes in morphology to alteration in gliotransmitter release. It is however unclear how astrocytic plasticity contributes to the neuronal EDP. Here, we review the known and possible roles for astrocytes in the barrel cortex, including its plasticity. PMID:26345481

Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

PubMed

Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

2015-12-09

In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DAT(IREScre) mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome. Dopamine neurons are important for the control of motivated behavior and are involved in the pathophysiology of several major neuropsychiatric disorders. Recent studies have shown that some ventral midbrain dopamine neurons are capable of glutamate cotransmission. With conditional expression of channelrhodopsin in dopamine neurons, we systematically explored dopamine neuron connections in the forebrain and identified regionally specific dopamine neuron excitatory connections. Establishing that only a subset of forebrain regions receive excitatory connections from dopamine neurons will help to determine the function of dopamine neuron glutamate cotransmission, which likely involves transmission of precise temporal signals and enhancement of the dynamic range of dopamine neuron signals. Copyright © 2015 the authors 0270-6474/15/3516259-13$15.00/0.

Multineuronal vectorization is more efficient than time-segmental vectorization for information extraction from neuronal activities in the inferior temporal cortex.

PubMed

Kaneko, Hidekazu; Tamura, Hiroshi; Tate, Shunta; Kawashima, Takahiro; Suzuki, Shinya S; Fujita, Ichiro

2010-08-01

In order for patients with disabilities to control assistive devices with their own neural activity, multineuronal spike trains must be efficiently decoded because only limited computational resources can be used to generate prosthetic control signals in portable real-time applications. In this study, we compare the abilities of two vectorizing procedures (multineuronal and time-segmental) to extract information from spike trains during the same total neuron-seconds. In the multineuronal vectorizing procedure, we defined a response vector whose components represented the spike counts of one to five neurons. In the time-segmental vectorizing procedure, a response vector consisted of components representing a neuron's spike counts for one to five time-segment(s) of a response period of 1 s. Spike trains were recorded from neurons in the inferior temporal cortex of monkeys presented with visual stimuli. We examined whether the amount of information of the visual stimuli carried by these neurons differed between the two vectorizing procedures. The amount of information calculated with the multineuronal vectorizing procedure, but not the time-segmental vectorizing procedure, significantly increased with the dimensions of the response vector. We conclude that the multineuronal vectorizing procedure is superior to the time-segmental vectorizing procedure in efficiently extracting information from neuronal signals. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation

NASA Astrophysics Data System (ADS)

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2015-08-01

Objective. Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. Approach. Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject’s cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. Main results. This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. Significance. These results provide critical new understanding of the factors by which TMS induces cortical activation necessary for predictive and repeatable use of this noninvasive stimulation modality.

Stimulus-induced dissociation of neuronal firing rates and local field potential gamma power and its relationship to the blood oxygen level-dependent signal in macaque primary visual cortex

PubMed Central

Bartolo, M J; Gieselmann, M A; Vuksanovic, V; Hunter, D; Sun, L; Chen, X; Delicato, L S; Thiele, A

2011-01-01

The functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) signal is regularly used to assign neuronal activity to cognitive function. Recent analyses have shown that the local field potential (LFP) gamma power is a better predictor of the fMRI BOLD signal than spiking activity. However, LFP gamma power and spiking activity are usually correlated, clouding the analysis of the neural basis of the BOLD signal. We show that changes in LFP gamma power and spiking activity in the primary visual cortex (V1) of the awake primate can be dissociated by using grating and plaid pattern stimuli, which differentially engage surround suppression and cross-orientation inhibition/facilitation within and between cortical columns. Grating presentation yielded substantial V1 LFP gamma frequency oscillations and significant multi-unit activity. Plaid pattern presentation significantly reduced the LFP gamma power while increasing population multi-unit activity. The fMRI BOLD activity followed the LFP gamma power changes, not the multi-unit activity. Inference of neuronal activity from the fMRI BOLD signal thus requires detailed a priori knowledge of how different stimuli or tasks activate the cortical network. PMID:22081989

Linear summation of outputs in a balanced network model of motor cortex.

PubMed

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis.

Magnetoencephalography Study of Right Parietal Lobe Dysfunction of the Evoked Mirror Neuron System in Antipsychotic-Free Schizophrenia

PubMed Central

Kato, Yutaka; Muramatsu, Taro; Kato, Motoichiro; Shibukawa, Yoshiyuki; Shintani, Masuro; Mimura, Masaru

2011-01-01

Introduction Patients with schizophrenia commonly exhibit deficits of non-verbal communication in social contexts, which may be related to cognitive dysfunction that impairs recognition of biological motion. Although perception of biological motion is known to be mediated by the mirror neuron system, there have been few empirical studies of this system in patients with schizophrenia. Methods Using magnetoencephalography, we examined whether antipsychotic-free schizophrenia patients displayed mirror neuron system dysfunction during observation of biological motion (jaw movement of another individual). Results Compared with normal controls, the patients with schizophrenia had fewer components of both the waveform and equivalent current dipole, suggesting aberrant brain activity resulting from dysfunction of the right inferior parietal cortex. They also lacked the changes of alpha band and gamma band oscillation seen in normal controls, and had weaker phase-locking factors and gamma-synchronization predominantly in right parietal cortex. Conclusions Our findings demonstrate that untreated patients with schizophrenia exhibit aberrant mirror neuron system function based on the right inferior parietal cortex, which is characterized by dysfunction of gamma-synchronization in the right parietal lobe during observation of biological motion. PMID:22132217

Electrical Stimulation of the Ear, Head, Cranial Nerve, or Cortex for the Treatment of Tinnitus: A Scoping Review

PubMed Central

Adjamian, Peyman

2016-01-01

Tinnitus is defined as the perception of sound in the absence of an external source. It is often associated with hearing loss and is thought to result from abnormal neural activity at some point or points in the auditory pathway, which is incorrectly interpreted by the brain as an actual sound. Neurostimulation therapies therefore, which interfere on some level with that abnormal activity, are a logical approach to treatment. For tinnitus, where the pathological neuronal activity might be associated with auditory and other areas of the brain, interventions using electromagnetic, electrical, or acoustic stimuli separately, or paired electrical and acoustic stimuli, have been proposed as treatments. Neurostimulation therapies should modulate neural activity to deliver a permanent reduction in tinnitus percept by driving the neuroplastic changes necessary to interrupt abnormal levels of oscillatory cortical activity and restore typical levels of activity. This change in activity should alter or interrupt the tinnitus percept (reduction or extinction) making it less bothersome. Here we review developments in therapies involving electrical stimulation of the ear, head, cranial nerve, or cortex in the treatment of tinnitus which demonstrably, or are hypothesised to, interrupt pathological neuronal activity in the cortex associated with tinnitus. PMID:27403346

Transformation of the neural code for tactile detection from thalamus to cortex.

PubMed

Vázquez, Yuriria; Salinas, Emilio; Romo, Ranulfo

2013-07-09

To understand how sensory-driven neural activity gives rise to perception, it is essential to characterize how various relay stations in the brain encode stimulus presence. Neurons in the ventral posterior lateral (VPL) nucleus of the somatosensory thalamus and in primary somatosensory cortex (S1) respond to vibrotactile stimulation with relatively slow modulations (∼100 ms) of their firing rate. In addition, faster modulations (∼10 ms) time-locked to the stimulus waveform are observed in both areas, but their contribution to stimulus detection is unknown. Furthermore, it is unclear whether VPL and S1 neurons encode stimulus presence with similar accuracy and via the same response features. To address these questions, we recorded single neurons while trained monkeys judged the presence or absence of a vibrotactile stimulus of variable amplitude, and their activity was analyzed with a unique decoding method that is sensitive to the time scale of the firing rate fluctuations. We found that the maximum detection accuracy of single neurons is similar in VPL and S1. However, VPL relies more heavily on fast rate modulations than S1, and as a consequence, the neural code in S1 is more tolerant: its performance degrades less when the readout method or the time scale of integration is suboptimal. Therefore, S1 neurons implement a more robust code, one less sensitive to the temporal integration window used to infer stimulus presence downstream. The differences between VPL and S1 responses signaling the appearance of a stimulus suggest a transformation of the neural code from thalamus to cortex.

A role for the anterior insular cortex in the global neuronal workspace model of consciousness.

PubMed

Michel, Matthias

2017-03-01

According to the global neuronal workspace model of consciousness, consciousness results from the global broadcast of information throughout the brain. The global neuronal workspace is mainly constituted by a fronto-parietal network. The anterior insular cortex is part of this global neuronal workspace, but the function of this region has not yet been defined within the global neuronal workspace model of consciousness. In this review, I hypothesize that the anterior insular cortex implements a cross-modal priority map, the function of which is to determine priorities for the processing of information and subsequent entrance in the global neuronal workspace. Copyright © 2017 Elsevier Inc. All rights reserved.

Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry

PubMed Central

2015-01-01

Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex. PMID:26719085

Measurement of cerebral blood flow rate and its relationship with brain function using optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Jian; Wang, Yi; Zhao, Yuqian; Dou, Shidan; Ma, Yushu; Ma, Zhenhe

2016-03-01

Activity of brain neurons will lead to changes in local blood flow rate (BFR). Thus, it is important to measure the local BFR of cerebral cortex on research of neuron activity in vivo, such as rehabilitation evaluation after stroke, etc. Currently, laser Doppler flowmetry is commonly used for blood flow measurement, however, relatively low resolution limits its application. Optical coherence tomography (OCT) is a powerful noninvasive 3D imaging modality with high temporal and spatial resolutions. Furthermore, OCT can provide flow distribution image by calculating Doppler frequency shift which makes it possible for blood flow rate measurement. In this paper, we applied OCT to measure the blood flow rate of the primary motor cortex in rats. The animal was immobilized and anesthetized with isoflurane, an incision was made along the sagittal suture, and bone was exposed. A skull window was opened on the primary motor cortex. Then, blood flow rate changes in the primary motor cortex were monitored by our homemade spectral domain OCT with a stimulation of the passive movement of the front legs. Finally, we established the relationship between blood flow rate and the test design. The aim is to demonstrate the potential of OCT in the evaluation of cerebral cortex function.

[Facial nerve injuries cause changes in central nervous system microglial cells].

PubMed

Cerón, Jeimmy; Troncoso, Julieta

2016-12-01

Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

A radial map of multi-whisker correlation selectivity in the rat barrel cortex

PubMed Central

Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E.; Bourdieu, Laurent; Léger, Jean- François

2016-01-01

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel–septal borders, forming rings of multi-whisker synchrony-preferring cells. PMID:27869114

A radial map of multi-whisker correlation selectivity in the rat barrel cortex.

PubMed

Estebanez, Luc; Bertherat, Julien; Shulz, Daniel E; Bourdieu, Laurent; Léger, Jean-François

2016-11-21

In the barrel cortex, several features of single-whisker stimuli are organized in functional maps. The barrel cortex also encodes spatio-temporal correlation patterns of multi-whisker inputs, but so far the cortical mapping of neurons tuned to such input statistics is unknown. Here we report that layer 2/3 of the rat barrel cortex contains an additional functional map based on neuronal tuning to correlated versus uncorrelated multi-whisker stimuli: neuron responses to uncorrelated multi-whisker stimulation are strongest above barrel centres, whereas neuron responses to correlated and anti-correlated multi-whisker stimulation peak above the barrel-septal borders, forming rings of multi-whisker synchrony-preferring cells.

Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output.

PubMed

Schiemann, Julia; Puggioni, Paolo; Dacre, Joshua; Pelko, Miha; Domanski, Aleksander; van Rossum, Mark C W; Duguid, Ian

2015-05-26

Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Neural correlates of conversion disorder: overview and meta-analysis of neuroimaging studies on motor conversion disorder.

PubMed

Boeckle, Markus; Liegl, Gregor; Jank, Robert; Pieh, Christoph

2016-06-10

Conversion Disorders (CD) are prevalent functional disorders. Although the pathogenesis is still not completely understood, an interaction of genetic, neurobiological, and psychosocial factors is quite likely. The aim of this study is to provide a systematic overview on imaging studies on CDs and investigate neuronal areas involved in Motor Conversion Disorders (MCD). A systematic literature search was conducted on CD. Subsequently a meta-analysis of functional neuroimaging studies on MCD was implemented using an Activation Likelihood Estimation (ALE). We calculated differences between patients and healthy controls as well as between affected versus unaffected sides in addition to an overall analysis in order to identify neuronal areas related to MCD. Patients with MCD differ from healthy controls in the amygdala, superior temporal lobe, retrosplenial area, primary motor cortex, insula, red nucleus, thalamus, anterior as well as dorsolateral prefrontal and frontal cortex. When comparing affected versus unaffected sides, temporal cortex, dorsal anterior cingulate cortex, supramarginal gyrus, dorsal temporal lobe, anterior insula, primary somatosensory cortex, superior frontal gyrus and anterior prefrontal as well as frontal cortex show significant differences. Neuronal areas seem to be involved in the pathogenesis, maintenance or as a result of MCD. Areas that are important for motor-planning, motor-selection or autonomic response seem to be especially relevant. Our results support the emotional unawareness theory but also underline the need of more support by conduction imaging studies on both CD and MCD.

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome.

PubMed

Huang, Wen-Chin; Chen, Youjun; Page, Damon T

2016-11-15

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten +/- ), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten +/- mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC-BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling.

Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome

PubMed Central

Huang, Wen-Chin; Chen, Youjun; Page, Damon T.

2016-01-01

Multiple autism risk genes converge on the regulation of mTOR signalling, which is a key effector of neuronal growth and connectivity. We show that mTOR signalling is dysregulated during early postnatal development in the cerebral cortex of germ-line heterozygous Pten mutant mice (Pten+/−), which model macrocephaly/autism syndrome. The basolateral amygdala (BLA) receives input from subcortical-projecting neurons in the medial prefrontal cortex (mPFC). Analysis of mPFC to BLA axonal projections reveals that Pten+/− mice exhibit increased axonal branching and connectivity, which is accompanied by increased activity in the BLA in response to social stimuli and social behavioural deficits. The latter two phenotypes can be suppressed by pharmacological inhibition of S6K1 during early postnatal life or by reducing the activity of mPFC–BLA circuitry in adulthood. These findings identify a mechanism of altered connectivity that has potential relevance to the pathophysiology of macrocephaly/autism syndrome and autism spectrum disorders featuring dysregulated mTOR signalling. PMID:27845329

Localization of the peroxisome proliferator-activated receptor in the brain.

PubMed

Kainu, T; Wikström, A C; Gustafsson, J A; Pelto-Huikko, M

1994-12-20

This paper describes the localization of the alpha-type peroxisome proliferator-activated receptor (PPAR alpha) in the rat brain using immunocytochemistry and in situ hybridization. Expression of PPAR alpha mRNA was highest in the granular cells of the cerebellar cortex and in the dentate gyrus, with a somewhat lower expression in areas CA1-CA4 of the hippocampus. PPAR alpha mRNA was also found in some neurones of the cerebral cortex (layers II-IV) and the molecular layer of the cerebellar cortex, and in the olfactory tubercle. Immunocytochemistry revealed nuclear PPAR alpha-immunoreactivity (-IR) in the same areas as seen with the in situ hybridization. Furthermore, PPAR alpha-IR was also localized in oligodendrocytes, whereas the other glial cell types appeared to lack PPAR alpha. These results suggest that peroxisome proliferators and chemicals acting similarly have effects on discrete populations of neurones. The presence of PPAR alpha in oligodendrocytes lends further support to the suggestion that peroxisomes are important in the assembly and degradation of myelin.

Internal state of monkey primary visual cortex (V1) predicts figure-ground perception.

PubMed

Supèr, Hans; van der Togt, Chris; Spekreijse, Henk; Lamme, Victor A F

2003-04-15

When stimulus information enters the visual cortex, it is rapidly processed for identification. However, sometimes the processing of the stimulus is inadequate and the subject fails to notice the stimulus. Human psychophysical studies show that this occurs during states of inattention or absent-mindedness. At a neurophysiological level, it remains unclear what these states are. To study the role of cortical state in perception, we analyzed neural activity in the monkey primary visual cortex before the appearance of a stimulus. We show that, before the appearance of a reported stimulus, neural activity was stronger and more correlated than for a not-reported stimulus. This indicates that the strength of neural activity and the functional connectivity between neurons in the primary visual cortex participate in the perceptual processing of stimulus information. Thus, to detect a stimulus, the visual cortex needs to be in an appropriate state.

Calretinin and parvalbumin immunoreactive interneurons in the retrosplenial cortex of the rat brain: Qualitative and quantitative analyses.

PubMed

Salaj, Martin; Druga, Rastislav; Cerman, Jiří; Kubová, Hana; Barinka, Filip

2015-11-19

The retrosplenial cortex (RSC) is a mesocortical region broadly involved with memory and navigation. It shares many characteristics with the perirhinal cortex (PRC), both of which appear to be significantly involved in the spreading of epileptic activity. We hypothesized that RSC possesses an interneuronal composition similar to that of PRC. To prove the hypothesis we studied the general pattern of calretinin (CR) and parvalbumin (PV) immunoreactivity in the RSC of the rat brain, its optical density as well as the morphological features and density of CR- and PV-immunoreactive (CR+ and PV+) interneurons. We also analyzed the overall neuronal density on Nissl-stained sections in RSC. Finally, we compared our results with our earlier analysis of PRC (Barinka et al., 2012). Compared to PRC, RSC was observed to have a higher intensity of PV staining and lower intensity of CR staining of neuropil. Vertically-oriented bipolar neurons were the most common morphological type among CR+ neurons. The staining pattern did not allow for a similarly detailed analysis of somatodendritic morphology of PV+ neurons. RSC possessed lower absolute (i.e., neurons/mm(3)) and relative (i.e., percentage of the overall neuronal population) densities of CR+ neurons and similar absolute and lower relative densities of PV+ neurons relative to PRC. CR: PV neuronal ratio in RSC (1:2 in area 29 and 1:2.2 in area 30) differed from PRC (1:1.2 in area 35 and 1:1.7 in area 36). In conclusion, RSC, although similar in many aspects to PRC, differs strikingly in the interneuronal composition relative to PRC. Copyright © 2015 Elsevier B.V. All rights reserved.

Opposing Effects of Acute versus Chronic Blockade of Frontal Cortex Somatostatin-Positive Inhibitory Neurons on Behavioral Emotionality in Mice

PubMed Central

Soumier, Amelie; Sibille, Etienne

2014-01-01

Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons. PMID:24690741

Opposing effects of acute versus chronic blockade of frontal cortex somatostatin-positive inhibitory neurons on behavioral emotionality in mice.

PubMed

Soumier, Amelie; Sibille, Etienne

2014-08-01

Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons.

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study

PubMed Central

Salustri, C.; Tecchio, F.; Zappasodi, F.; Tomasevic, L.; Ercolani, M.; Moffa, F.; Cassetta, E.; Rossini, P. M.; Squitti, R.

2013-01-01

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity. Results. Patients' sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission. Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD. Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia. PMID:24416615

Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine Craving.

PubMed

Funk, Douglas; Coen, Kathleen; Tamadon, Sahar; Hope, Bruce T; Shaham, Yavin; Lê, A D

2016-08-17

The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. Here, we further characterized incubation of nicotine craving in the rat model by determining whether this incubation is observed after adolescent-onset nicotine self-administration. We also used the neuronal activity marker Fos and the Daun02 chemogenetic inactivation procedure to identify cue-activated neuronal ensembles that mediate incubation of nicotine craving. We trained adolescent and adult male rats to self-administer nicotine (2 h/d for 12 d) and assessed cue-induced nicotine seeking in extinction tests (1 h) after 1, 7, 14, or 28 withdrawal days. In both adult and adolescent rats, nicotine seeking in the relapse tests followed an inverted U-shaped curve, with maximal responding on withdrawal day 14. Independent of the withdrawal day, nicotine seeking in the relapse tests was higher in adult than in adolescent rats. Analysis of Fos expression in different brain areas of adolescent and adult rats on withdrawal days 1 and 14 showed time-dependent increases in the number of Fos-positive neurons in central and basolateral amygdala, orbitofrontal cortex, ventral and dorsal medial prefrontal cortex, and nucleus accumbens core and shell. In adult Fos-lacZ transgenic rats, selective inactivation of nicotine-cue-activated Fos neurons in central amygdala, but not orbitofrontal cortex, decreased "incubated" nicotine seeking on withdrawal day 14. Our results demonstrate that incubation of nicotine craving occurs after adolescent-onset nicotine self-administration and that neuronal ensembles in central amygdala play a critical role in this incubation. The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. It is currently unknown whether incubation of craving also occurs after adolescent-onset nicotine self-administration. The brain areas that mediate such incubation are also unknown. Here, we used a rat model of incubation of drug craving, the neuronal activity marker Fos, and the Daun02 chemogenetic inactivation method to demonstrate that incubation of nicotine craving is also observed after adolescent-onset nicotine self-administration and that neuronal ensembles in the central nucleus of the amygdala play a critical role in this incubation in adult rats. Copyright © 2016 the authors 0270-6474/16/368612-12$15.00/0.

Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine Craving

PubMed Central

Coen, Kathleen; Tamadon, Sahar; Hope, Bruce T.; Shaham, Yavin; Lê, A.D.

2016-01-01

The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. Here, we further characterized incubation of nicotine craving in the rat model by determining whether this incubation is observed after adolescent-onset nicotine self-administration. We also used the neuronal activity marker Fos and the Daun02 chemogenetic inactivation procedure to identify cue-activated neuronal ensembles that mediate incubation of nicotine craving. We trained adolescent and adult male rats to self-administer nicotine (2 h/d for 12 d) and assessed cue-induced nicotine seeking in extinction tests (1 h) after 1, 7, 14, or 28 withdrawal days. In both adult and adolescent rats, nicotine seeking in the relapse tests followed an inverted U-shaped curve, with maximal responding on withdrawal day 14. Independent of the withdrawal day, nicotine seeking in the relapse tests was higher in adult than in adolescent rats. Analysis of Fos expression in different brain areas of adolescent and adult rats on withdrawal days 1 and 14 showed time-dependent increases in the number of Fos-positive neurons in central and basolateral amygdala, orbitofrontal cortex, ventral and dorsal medial prefrontal cortex, and nucleus accumbens core and shell. In adult Fos–lacZ transgenic rats, selective inactivation of nicotine-cue-activated Fos neurons in central amygdala, but not orbitofrontal cortex, decreased “incubated” nicotine seeking on withdrawal day 14. Our results demonstrate that incubation of nicotine craving occurs after adolescent-onset nicotine self-administration and that neuronal ensembles in central amygdala play a critical role in this incubation. SIGNIFICANCE STATEMENT The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. It is currently unknown whether incubation of craving also occurs after adolescent-onset nicotine self-administration. The brain areas that mediate such incubation are also unknown. Here, we used a rat model of incubation of drug craving, the neuronal activity marker Fos, and the Daun02 chemogenetic inactivation method to demonstrate that incubation of nicotine craving is also observed after adolescent-onset nicotine self-administration and that neuronal ensembles in the central nucleus of the amygdala play a critical role in this incubation in adult rats. PMID:27535909

Modulation of Craving Related Brain Responses Using Real-Time fMRI in Patients with Alcohol Use Disorder

PubMed Central

Hümmer, Sebastian; Paolini, Marco; Kirsch, Valerie; Karali, Temmuz; Kupka, Michael; Rauchmann, Boris-Stephan; Chrobok, Agnieszka; Blautzik, Janusch; Koller, Gabi; Ertl-Wagner, Birgit; Pogarell, Oliver

2015-01-01

Literature One prominent symptom in addiction disorders is the strong desire to consume a particular substance or to display a certain behaviour (craving). Especially the strong association between craving and the probability of relapse emphasises the importance of craving in the therapeutic process. Neuroimaging studies have shown that craving is associated with increased responses, predominantly in fronto-striatal areas. Aim and Methods The aim of the present study is the modification of craving-related neuronal responses in patients with alcohol addiction using fMRI real-time neurofeedback. For that purpose, patients with alcohol use disorder and healthy controls participated once in neurofeedback training; during the sessions neuronal activity within an individualized cortical region of interest (ROI) (anterior cingulate cortex, insula, dorsolateral prefrontal cortex) was evaluated. In addition, variations regarding the connectivity between brain regions were assessed in the resting state. Results and Discussion The results showed a significant reduction of neuronal activity in patients at the end of the training compared to the beginning, especially in the anterior cingulate cortex, the insula, the inferior temporal gyrus and the medial frontal gyrus. Furthermore, the results show that patients were able to regulate their neuronal activities in the ROI, whereas healthy subjects achieved no significant reduction. However, there was a wide variability regarding the effects of the training within the group of patients. After the neurofeedback-sessions, individual craving was slightly reduced compared to baseline. The results demonstrate that it seems feasible for patients with alcohol dependency to reduce their neuronal activity using rtfMRI neurofeedback. In addition, there is some evidence that craving can be influenced with the help of this technique. Future Prospects In future, real-time fMRI might be a complementary neurophysiological-based strategy for the psychotherapy of patients with psychiatric or psychosomatic diseases. For that purpose, the stability of this effect and the generalizability needs to be assessed. PMID:26204262

Mitochondrial dysfunction precedes depression of AMPK/AKT signaling in insulin resistance induced by high glucose in primary cortical neurons.

PubMed

Peng, Yunhua; Liu, Jing; Shi, Le; Tang, Ying; Gao, Dan; Long, Jiangang; Liu, Jiankang

2016-06-01

Recent studies have demonstrated brain insulin signaling impairment and mitochondrial dysfunction in diabetes. Hyperinsulinemia and hyperlipidemia arising from diabetes have been linked to neuronal insulin resistance, and hyperglycemia induces peripheral sensory neuronal impairment and mitochondrial dysfunction. However, how brain glucose at diabetic conditions elicits cortical neuronal insulin signaling impairment and mitochondrial dysfunction remains unknown. In the present study, we cultured primary cortical neurons with high glucose levels and investigated the neuronal mitochondrial function and insulin response. We found that mitochondrial function was declined in presence of 10 mmol/L glucose, prior to the depression of AKT signaling in primary cortical neurons. We further demonstrated that the cerebral cortex of db/db mice exhibited both insulin resistance and loss of mitochondrial complex components. Moreover, we found that adenosine monophosphate-activated protein kinase (AMPK) inactivation is involved in high glucose-induced mitochondrial dysfunction and insulin resistance in primary cortical neurons and neuroblastoma cells, as well as in cerebral cortex of db/db mice, and all these impairments can be rescued by mitochondrial activator, resveratrol. Taken together, our results extend the finding that high glucose (≥10 mmol/L) comparable to diabetic brain extracellular glucose level leads to neuronal mitochondrial dysfunction and resultant insulin resistance, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. We found that high glucose (≥10 mmol/L), comparable to diabetic brain extracellular glucose level, leads to neuronal mitochondrial dysfunction and resultant insulin resistance in an AMPK-dependent manner, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. © 2016 International Society for Neurochemistry.

Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen.

PubMed

Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin

2013-02-01

Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca(2+) waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O(2) tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca(2+) activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.

Effect of D-cycloserine in conjunction with fear extinction training on extracellular signal-regulated kinase activation in the medial prefrontal cortex and amygdala in rat.

PubMed

Gupta, Subhash C; Hillman, Brandon G; Prakash, Anand; Ugale, Rajesh R; Stairs, Dustin J; Dravid, Shashank M

2013-06-01

D-cycloserine (DCS) is currently under clinical trials for a number of neuropsychiatric conditions and has been found to augment fear extinction in rodents and exposure therapy in humans. However, the molecular mechanism of DCS action in these multiple modalities remains unclear. Here, we describe the effect of DCS administration, alone or in conjunction with extinction training, on neuronal activity (c-fos) and neuronal plasticity [phospho-extracellular signal-regulated kinase (pERK)] markers using immunohistochemistry. We found that intraperitoneal administration of DCS in untrained young rats (24-28 days old) increased c-fos- and pERK-stained neurons in both the prelimbic and infralimbic division of the medial prefrontal cortex (mPFC) and reduced pERK levels in the lateral nucleus of the central amygdala. Moreover, DCS administration significantly increased GluA1, GluN1, GluN2A, and GluN2B expression in the mPFC. In a separate set of animals, we found that DCS facilitated fear extinction and increased pERK levels in the infralimbic prefrontal cortex, prelimbic prefrontal cortex intercalated cells and lateral nucleus of the central amygdala, compared with saline control. In the synaptoneurosomal preparation, we found that extinction training increased iGluR protein expression in the mPFC, compared with context animals. No significant difference in protein expression was observed between extinction-saline and extinction-DCS groups in the mPFC. In contrast, in the amygdala DCS, the conjunction with extinction training led to an increase in iGluR subunit expression, compared with the extinction-saline group. Our data suggest that the efficacy of DCS in neuropsychiatric disorders may be partly due to its ability to affect neuronal activity and signaling in the mPFC and amygdala subnuclei. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Individual Variations in Maternal Care Early in Life Correlate with Later Life Decision-Making and c-Fos Expression in Prefrontal Subregions of Rats

PubMed Central

van Hasselt, Felisa N.; de Visser, Leonie; Tieskens, Jacintha M.; Cornelisse, Sandra; Baars, Annemarie M.; Lavrijsen, Marla; Krugers, Harm J.; van den Bos, Ruud; Joëls, Marian

2012-01-01

Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology–e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures. PMID:22693577

Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex.

PubMed

Piché, Marilyse; Thomas, Sébastien; Casanova, Christian

2015-10-01

The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex. Copyright © 2015 the American Physiological Society.

In vitro Neurons in Mammalian Cortical Layer 4 Exhibit Intrinsic Oscillatory Activity in the 10- to 50-Hz Frequency Range

NASA Astrophysics Data System (ADS)

Llinas, Rodolfo R.; Grace, Anthony A.; Yarom, Yosef

1991-02-01

We report here the presence of fast subthreshold oscillatory potentials recorded in vitro from neurons within layer 4 of the guinea pig frontal cortex. Two types of oscillatory neurons were recorded: (i) One type exhibited subthreshold oscillations whose frequency increased with membrane depolarization and encompassed a range of 10-45 Hz. Action potentials in this type of neuron demonstrated clear after-hyperpolarizations. (ii) The second type of neuron was characterized by narrow-frequency oscillations near 35-50 Hz. These oscillations often outlasted the initiating depolarizing stimulus. No calcium component could be identified in their action potential. In both types of cell the subthreshold oscillations were tetrodotoxin-sensitive, indicating that the depolarizing phase of the oscillation was generated by a voltage-dependent sodium conductance. The initial depolarizing phase was followed by a potassium conductance responsible for the falling phase of the oscillatory wave. In both types of cell, the subthreshold oscillation could trigger spikes at the oscillatory frequency, if the membrane was sufficiently depolarized. Combining intracellular recordings with Lucifer yellow staining showed that the narrow-frequency oscillatory activity was produced by a sparsely spinous interneuron located in layer 4 of the cortex. This neuron has extensive local axonal collaterals that ramify in layers 3 and 4 such that they may contribute to the columnar synchronization of activity in the 40- to 50-Hz range. Cortical activity in this frequency range has been proposed as the basis for the "conjunctive properties" of central nervous system networks.

Taste, olfactory, and food reward value processing in the brain.

PubMed

Rolls, Edmund T

2015-04-01

Complementary neuronal recordings in primates, and functional neuroimaging in humans, show that the primary taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture (including fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in a second tier of processing, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by associative learning with olfactory and visual inputs, and these neurons encode food reward value on a continuous scale in that they only respond to food when hungry, and in that activations correlate linearly with subjective pleasantness. Cognitive factors, including word-level descriptions, and selective attention to affective value, modulate the representation of the reward value of taste and olfactory stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex, a tertiary taste cortical area. The food reward representations formed in this way play an important role in the control of appetite, and food intake. Individual differences in these reward representations may contribute to obesity, and there are age-related differences in these value representations that shape the foods that people in different age groups find palatable. In a third tier of processing in medial prefrontal cortex area 10, decisions between stimuli of different reward value are taken, by attractor decision-making networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting the Arntl Clock Gene in Cortical Neurons.

PubMed

Bering, Tenna; Carstensen, Mikkel Bloss; Wörtwein, Gitta; Weikop, Pia; Rath, Martin Fredensborg

2018-02-01

A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically in an extrahypothalamic cell type of the brain. Molecular analyses of clock gene expression in the cerebral cortex of the Arntl conditional knockout mouse revealed disrupted circadian expression profiles, whereas clock gene expression in the suprachiasmatic nucleus was still rhythmic, thus showing that Arntl is required for normal function of the cortical circadian oscillator. Daily rhythms in running activity and temperature were not influenced, whereas the resynchronization response to experimental jet-lag exhibited minor though significant differences between genotypes. The tail-suspension test revealed significantly prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Prefrontal Contribution to Decision-Making under Free-Choice Conditions

PubMed Central

Funahashi, Shintaro

2017-01-01

Executive function is thought to be the coordinated operation of multiple neural processes and allows to accomplish a current goal flexibly. The most important function of the prefrontal cortex is the executive function. Among a variety of executive functions in which the prefrontal cortex participates, decision-making is one of the most important. Although the prefrontal contribution to decision-making has been examined using a variety of behavioral tasks, recent studies using fMRI have shown that the prefrontal cortex participates in decision-making under free-choice conditions. Since decision-making under free-choice conditions represents the very first stage for any kind of decision-making process, it is important that we understand its neural mechanism. Although few studies have examined this issue while a monkey performed a free-choice task, those studies showed that, when the monkey made a decision to subsequently choose one particular option, prefrontal neurons showing selectivity to that option exhibited transient activation just before presentation of the imperative cue. Further studies have suggested that this transient increase is caused by the irregular fluctuation of spontaneous firing just before cue presentation, which enhances the response to the cue and biases the strength of the neuron's selectivity to the option. In addition, this biasing effect was observed only in neurons that exhibited sustained delay-period activity, indicating that this biasing effect not only influences the animal's decision for an upcoming choice, but also is linked to working memory mechanisms in the prefrontal cortex. PMID:28798662

Spectral and Temporal Processing in Rat Posterior Auditory Cortex

PubMed Central

Pandya, Pritesh K.; Rathbun, Daniel L.; Moucha, Raluca; Engineer, Navzer D.; Kilgard, Michael P.

2009-01-01

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing between these areas. To determine the filter properties of rat posterior auditory field (PAF) neurons, we compared neurophysiological responses to simple tones, frequency modulated (FM) sweeps, and amplitude modulated noise and tones with responses of primary auditory cortex (A1) neurons. PAF neurons have excitatory receptive fields that are on average 65% broader than A1 neurons. The broader receptive fields of PAF neurons result in responses to narrow and broadband inputs that are stronger than A1. In contrast to A1, we found little evidence for an orderly topographic gradient in PAF based on frequency. These neurons exhibit latencies that are twice as long as A1. In response to modulated tones and noise, PAF neurons adapt to repeated stimuli at significantly slower rates. Unlike A1, neurons in PAF rarely exhibit facilitation to rapidly repeated sounds. Neurons in PAF do not exhibit strong selectivity for rate or direction of narrowband one octave FM sweeps. These results indicate that PAF, like nonprimary visual fields, processes sensory information on larger spectral and longer temporal scales than primary cortex. PMID:17615251

Decoding complete reach and grasp actions from local primary motor cortex populations.

PubMed

Vargas-Irwin, Carlos E; Shakhnarovich, Gregory; Yadollahpour, Payman; Mislow, John M K; Black, Michael J; Donoghue, John P

2010-07-21

How the activity of populations of cortical neurons generates coordinated multijoint actions of the arm, wrist, and hand is poorly understood. This study combined multielectrode recording techniques with full arm motion capture to relate neural activity in primary motor cortex (M1) of macaques (Macaca mulatta) to arm, wrist, and hand postures during movement. We find that the firing rate of individual M1 neurons is typically modulated by the kinematics of multiple joints and that small, local ensembles of M1 neurons contain sufficient information to reconstruct 25 measured joint angles (representing an estimated 10 functionally independent degrees of freedom). Beyond showing that the spiking patterns of local M1 ensembles represent a rich set of naturalistic movements involving the entire upper limb, the results also suggest that achieving high-dimensional reach and grasp actions with neuroprosthetic devices may be possible using small intracortical arrays like those already being tested in human pilot clinical trials.

Reduced Spiking in Entorhinal Cortex during the Delay Period of a Cued Spatial Response Task

ERIC Educational Resources Information Center

Gupta, Kishan; Keller, Lauren A.; Hasselmo, Michael E.

2012-01-01

Intrinsic persistent spiking mechanisms in medial entorhinal cortex (mEC) neurons may play a role in active maintenance of working memory. However, electrophysiological studies of rat mEC units have primarily focused on spatial modulation. We sought evidence of differential spike rates in the mEC in rats trained on a T-maze, cued spatial delayed…

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory

PubMed Central

Bastos, André M.; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K.

2018-01-01

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50–250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4–22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. PMID:29339471

Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory.

PubMed

Bastos, André M; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K

2018-01-30

All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. Copyright © 2018 the Author(s). Published by PNAS.

Sensory Prioritization in Rats: Behavioral Performance and Neuronal Correlates.

PubMed

Lee, Conrad C Y; Diamond, Mathew E; Arabzadeh, Ehsan

2016-03-16

Operating with some finite quantity of processing resources, an animal would benefit from prioritizing the sensory modality expected to provide key information in a particular context. The present study investigated whether rats dedicate attentional resources to the sensory modality in which a near-threshold event is more likely to occur. We manipulated attention by controlling the likelihood with which a stimulus was presented from one of two modalities. In a whisker session, 80% of trials contained a brief vibration stimulus applied to whiskers and the remaining 20% of trials contained a brief change of luminance. These likelihoods were reversed in a visual session. When a stimulus was presented in the high-likelihood context, detection performance increased and was faster compared with the same stimulus presented in the low-likelihood context. Sensory prioritization was also reflected in neuronal activity in the vibrissal area of primary somatosensory cortex: single units responded differentially to the whisker vibration stimulus when presented with higher probability compared with lower probability. Neuronal activity in the vibrissal cortex displayed signatures of multiplicative gain control and enhanced response to vibration stimuli during the whisker session. In conclusion, rats allocate priority to the more likely stimulus modality and the primary sensory cortex may participate in the redistribution of resources. Detection of low-amplitude events is critical to survival; for example, to warn prey of predators. To formulate a response, decision-making systems must extract minute neuronal signals from the sensory modality that provides key information. Here, we identify the behavioral and neuronal correlates of sensory prioritization in rats. Rats were trained to detect whisker vibrations or visual flickers. Stimuli were embedded in two contexts in which either visual or whisker modality was more likely to occur. When a stimulus was presented in the high-likelihood context, detection was faster and more reliable. Neuronal recording from the vibrissal cortex revealed enhanced representation of vibrations in the prioritized context. These results establish the rat as an alternative model organism to primates for studying attention. Copyright © 2016 the authors 0270-6474/16/363243-11$15.00/0.

Interactions between attention, context and learning in primary visual cortex.

PubMed

Gilbert, C; Ito, M; Kapadia, M; Westheimer, G

2000-01-01

Attention in early visual processing engages the higher order, context dependent properties of neurons. Even at the earliest stages of visual cortical processing neurons play a role in intermediate level vision - contour integration and surface segmentation. The contextual influences mediating this process may be derived from long range connections within primary visual cortex (V1). These influences are subject to perceptual learning, and are strongly modulated by visuospatial attention, which is itself a learning dependent process. The attentional influences may involve interactions between feedback and horizontal connections in V1. V1 is therefore a dynamic and active processor, subject to top-down influences.

Neurons selective to the number of visual items in the corvid songbird endbrain

PubMed Central

Ditz, Helen M.; Nieder, Andreas

2015-01-01

It is unknown whether anatomical specializations in the endbrains of different vertebrates determine the neuronal code to represent numerical quantity. Therefore, we recorded single-neuron activity from the endbrain of crows trained to judge the number of items in displays. Many neurons were tuned for numerosities irrespective of the physical appearance of the items, and their activity correlated with performance outcome. Comparison of both behavioral and neuronal representations of numerosity revealed that the data are best described by a logarithmically compressed scaling of numerical information, as postulated by the Weber–Fechner law. The behavioral and neuronal numerosity representations in the crow reflect surprisingly well those found in the primate association cortex. This finding suggests that distantly related vertebrates with independently developed endbrains adopted similar neuronal solutions to process quantity. PMID:26056278

Decoding bipedal locomotion from the rat sensorimotor cortex.

PubMed

Rigosa, J; Panarese, A; Dominici, N; Friedli, L; van den Brand, R; Carpaneto, J; DiGiovanna, J; Courtine, G; Micera, S

2015-10-01

Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds, are likely to provide more robust control strategies for the design of such neuroprostheses.

Assessing the Role of Inhibition in Stabilizing Neocortical Networks Requires Large-Scale Perturbation of the Inhibitory Population

PubMed Central

Mrsic-Flogel, Thomas D.

2017-01-01

Neurons within cortical microcircuits are interconnected with recurrent excitatory synaptic connections that are thought to amplify signals (Douglas and Martin, 2007), form selective subnetworks (Ko et al., 2011), and aid feature discrimination. Strong inhibition (Haider et al., 2013) counterbalances excitation, enabling sensory features to be sharpened and represented by sparse codes (Willmore et al., 2011). This balance between excitation and inhibition makes it difficult to assess the strength, or gain, of recurrent excitatory connections within cortical networks, which is key to understanding their operational regime and the computations that they perform. Networks that combine an unstable high-gain excitatory population with stabilizing inhibitory feedback are known as inhibition-stabilized networks (ISNs) (Tsodyks et al., 1997). Theoretical studies using reduced network models predict that ISNs produce paradoxical responses to perturbation, but experimental perturbations failed to find evidence for ISNs in cortex (Atallah et al., 2012). Here, we reexamined this question by investigating how cortical network models consisting of many neurons behave after perturbations and found that results obtained from reduced network models fail to predict responses to perturbations in more realistic networks. Our models predict that a large proportion of the inhibitory network must be perturbed to reliably detect an ISN regime robustly in cortex. We propose that wide-field optogenetic suppression of inhibition under promoters targeting a large fraction of inhibitory neurons may provide a perturbation of sufficient strength to reveal the operating regime of cortex. Our results suggest that detailed computational models of optogenetic perturbations are necessary to interpret the results of experimental paradigms. SIGNIFICANCE STATEMENT Many useful computational mechanisms proposed for cortex require local excitatory recurrence to be very strong, such that local inhibitory feedback is necessary to avoid epileptiform runaway activity (an “inhibition-stabilized network” or “ISN” regime). However, recent experimental results suggest that this regime may not exist in cortex. We simulated activity perturbations in cortical networks of increasing realism and found that, to detect ISN-like properties in cortex, large proportions of the inhibitory population must be perturbed. Current experimental methods for inhibitory perturbation are unlikely to satisfy this requirement, implying that existing experimental observations are inconclusive about the computational regime of cortex. Our results suggest that new experimental designs targeting a majority of inhibitory neurons may be able to resolve this question. PMID:29074575

Temporal Dynamics of Parvalbumin-Expressing Axo-axonic and Basket Cells in the Rat Medial Prefrontal Cortex In Vivo

PubMed Central

Hartwich, Katja; Borhegyi, Zsolt; Somogyi, Peter; Klausberger, Thomas

2015-01-01

Axo-axonic interneurons, innervating exclusively axon initial segments, and parvalbumin-expressing basket interneurons, targeting somata, dendrites, and spines of pyramidal cells, have been proposed to control neuronal activity in prefrontal circuits. We recorded the spike-timing of identified neurons in the prelimbic cortex of anesthetized rats, and show that axo-axonic cells increase their firing during tail pinch-induced brain state-activation. In addition, axo-axonic cells differ from other GABAergic parvalbumin-expressing cells in their spike timing during DOWN- to UP-state transitions of slow oscillations and in their coupling to gamma and spindle oscillations. The distinct firing dynamics and synaptic targets of axo-axonic and other parvalbumin-expressing cells provide differential contributions to the temporal organization of prefrontal networks. PMID:23152631

Disruption of Prefrontal Cortex Large Scale Neuronal Activity by Different Classes of Psychotomimetic Drugs

PubMed Central

Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

2012-01-01

In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas the NMDA receptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spikerate and LFP power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease. PMID:22378875

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex

PubMed Central

Naumann, Robert K.; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L.

2016-01-01

ABSTRACT To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin‐positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin‐negative and calbindin‐positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin‐positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin‐positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10‐fold over a 20,000‐fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. J. Comp. Neurol. 524:783–806, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26223342

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex.

PubMed

Naumann, Robert K; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L; Brecht, Michael

2016-03-01

To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin-positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin-negative and calbindin-positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin-positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin-positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10-fold over a 20,000-fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Regulation of neuropeptide Y gene expression in rat brain.

PubMed

Lindefors, N; Brené, S; Herrera-Marschitz, M; Persson, H

1990-01-01

NPY mRNA expression was studied in rat brain using in situ hybridization and RNA blot analysis. Transsynaptic regulation of NPY gene expression was specifically studied in caudate-putamen and frontoparietal (somatosensory) cortex of rats with unilateral lesion of midbrain dopamine neurons and in sham-injected animals. NPY mRNA expression in these two brain regions and the regulation of midbrain dopamine neurons were compared with that of SOM, PPT, CCK and GAD mRNA expression. Neurons expressing NPY and SOM mRNA showed a similar distribution and the expression of both NPY and SOM appears to be regulated by dopamine in a similar fashion. Following a unilateral dopamine deafferentation, the numerical density of both NPY and SOM mRNA expressing neurons almost doubled in the lesioned rat caudate-putamen with no change in the average grain density over positive neurons. Hence, in the intact caudate-putamen dopamine appears to normally suppress expression of these two neuropeptide genes. An activation of both NPY and SOM mRNA expression in many non- or low-expressing neurons is seen when the level of dopamine is decreased. In the frontoparietal cortex, on the other hand, dopamine appears to stimulate NPY and SOM gene expression. RNA blot analysis shows clear-cut changes of NPY mRNA levels in both caudate-putamen and frontoparietal cortex consistent with the changes observed using in situ hybridization. No evidence was found for a change in CCK mRNA expression by the dopamine deafferentation, while PPT mRNA expression decreased in the deafferented caudate-putamen. Consequently, dopamine exerts dissimilar effects on the expression of different neuropeptide genes, that in turn do not respond in the same way in different brain regions. Indirect evidence is also presented indicating that dopamine regulates NPY mRNA expression in a subpopulation of neurons that possibly also express GAD mRNA, both in caudate-putamen and in frontoparietal cortex.

RNA-Sequencing Analysis Reveals a Regulatory Role for Transcription Factor Fezf2 in the Mature Motor Cortex

PubMed Central

Clare, Alison J.; Wicky, Hollie E.; Empson, Ruth M.; Hughes, Stephanie M.

2017-01-01

Forebrain embryonic zinc finger (Fezf2) encodes a transcription factor essential for the specification of layer 5 projection neurons (PNs) in the developing cerebral cortex. As with many developmental transcription factors, Fezf2 continues to be expressed into adulthood, suggesting it remains crucial to the maintenance of neuronal phenotypes. Despite the continued expression, a function has yet to be explored for Fezf2 in the PNs of the developed cortex. Here, we investigated the role of Fezf2 in mature neurons, using lentiviral-mediated delivery of a shRNA to conditionally knockdown the expression of Fezf2 in the mouse primary motor cortex (M1). RNA-sequencing analysis of Fezf2-reduced M1 revealed significant changes to the transcriptome, identifying a regulatory role for Fezf2 in the mature M1. Kyoto Encyclopedia Genes and Genomes (KEGG) pathway analyses of Fezf2-regulated genes indicated a role in neuronal signaling and plasticity, with significant enrichment of neuroactive ligand-receptor interaction, cell adhesion molecules and calcium signaling pathways. Gene Ontology analysis supported a functional role for Fezf2-regulated genes in neuronal transmission and additionally indicated an importance in the regulation of behavior. Using the mammalian phenotype ontology database, we identified a significant overrepresentation of Fezf2-regulated genes associated with specific behavior phenotypes, including associative learning, social interaction, locomotor activation and hyperactivity. These roles were distinct from that of Fezf2-regulated genes identified in development, indicating a dynamic transition in Fezf2 function. Together our findings demonstrate a regulatory role for Fezf2 in the mature brain, with Fezf2-regulated genes having functional roles in sustaining normal neuronal and behavioral phenotypes. These results support the hypothesis that developmental transcription factors are important for maintaining neuron transcriptomes and that disruption of their expression could contribute to the progression of disease phenotypes. PMID:28936162

Prolonged deficits in parvalbumin neuron stimulation-evoked network activity despite recovery of dendritic structure and excitability in the somatosensory cortex following global ischemia in mice.

PubMed

Xie, Yicheng; Chen, Shangbin; Wu, Yujin; Murphy, Timothy H

2014-11-05

Relatively few studies have examined plasticity of inhibitory neuronal networks following stroke in vivo, primarily due to the inability to selectively monitor inhibition. We assessed the structure of parvalbumin (PV) interneurons during a 5 min period of global ischemia and reperfusion in mice, which mimicked cerebral ischemia during cardiac arrest or forms of transient ischemic attack. The dendritic structure of PV-neurons in cortical superficial layers was rapidly swollen and beaded during global ischemia, but recovered within 5-10 min following reperfusion. Using optogenetics and a multichannel optrode, we investigated the function of PV-neurons in mouse forelimb somatosensory cortex. We demonstrated pharmacologically that PV-channelrhodopsin-2 (ChR2) stimulation evoked activation in layer IV/V, which resulted in rapid current sinks mediated by photocurrent and action potentials (a measure of PV-neuron excitability), which was then followed by current sources mediated by network GABAergic synaptic activity. During ischemic depolarization, the PV-ChR2-evoked current sinks (excitability) were suppressed, but recovered rapidly following reperfusion concurrent with repolarization of the DC-EEG. In contrast, the current sources reflecting GABAergic synaptic network activity recovered slowly and incompletely, and was coincident with the partial recovery of the forepaw stimulation-evoked current sinks in layer IV/V 30 min post reperfusion. Our in vivo data suggest that the excitability of PV inhibitory neurons was suppressed during global ischemia and rapidly recovered during reperfusion. In contrast, PV-ChR2 stimulation-evoked GABAergic synaptic network activity exhibited a prolonged suppression even ∼1 h after reperfusion, which could contribute to the dysfunction of sensation and cognition following transient global ischemia. Copyright © 2014 the authors 0270-6474/14/3414890-12$15.00/0.

Compensating Level-Dependent Frequency Representation in Auditory Cortex by Synaptic Integration of Corticocortical Input

PubMed Central

Happel, Max F. K.; Ohl, Frank W.

2017-01-01

Robust perception of auditory objects over a large range of sound intensities is a fundamental feature of the auditory system. However, firing characteristics of single neurons across the entire auditory system, like the frequency tuning, can change significantly with stimulus intensity. Physiological correlates of level-constancy of auditory representations hence should be manifested on the level of larger neuronal assemblies or population patterns. In this study we have investigated how information of frequency and sound level is integrated on the circuit-level in the primary auditory cortex (AI) of the Mongolian gerbil. We used a combination of pharmacological silencing of corticocortically relayed activity and laminar current source density (CSD) analysis. Our data demonstrate that with increasing stimulus intensities progressively lower frequencies lead to the maximal impulse response within cortical input layers at a given cortical site inherited from thalamocortical synaptic inputs. We further identified a temporally precise intercolumnar synaptic convergence of early thalamocortical and horizontal corticocortical inputs. Later tone-evoked activity in upper layers showed a preservation of broad tonotopic tuning across sound levels without shifts towards lower frequencies. Synaptic integration within corticocortical circuits may hence contribute to a level-robust representation of auditory information on a neuronal population level in the auditory cortex. PMID:28046062

Downstream effects of hippocampal sharp wave ripple oscillations on medial entorhinal cortex layer V neurons in vitro.

PubMed

Roth, Fabian C; Beyer, Katinka M; Both, Martin; Draguhn, Andreas; Egorov, Alexei V

2016-12-01

The entorhinal cortex (EC) is a critical component of the medial temporal lobe (MTL) memory system. Local networks within the MTL express a variety of state-dependent network oscillations that are believed to organize neuronal activity during memory formation. The peculiar pattern of sharp wave-ripple complexes (SPW-R) entrains neurons by a very fast oscillation at ∼200 Hz in the hippocampal areas CA3 and CA1 and then propagates through the "output loop" into the EC. The precise mechanisms of SPW-R propagation and the resulting cellular input patterns in the mEC are, however, largely unknown. We therefore investigated the activity of layer V (LV) principal neurons of the medial EC (mEC) during SPW-R oscillations in horizontal mouse brain slices. Intracellular recordings in the mEC were combined with extracellular monitoring of propagating network activity. SPW-R in CA1 were regularly followed by negative field potential deflections in the mEC. Propagation of SPW-R activity from CA1 to the mEC was mostly monosynaptic and excitatory, such that synaptic input to mEC LV neurons directly reflected unit activity in CA1. Comparison with propagating network activity from CA3 to CA1 revealed a similar role of excitatory long-range connections for both regions. However, SPW-R-induced activity in CA1 involved strong recruitment of rhythmic synaptic inhibition and corresponding fast field oscillations, in contrast to the mEC. These differences between features of propagating SPW-R emphasize the differential processing of network activity by each local network of the hippocampal output loop. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Tonic effects of the dopaminergic ventral midbrain on the auditory cortex of awake macaque monkeys.

PubMed

Huang, Ying; Mylius, Judith; Scheich, Henning; Brosch, Michael

2016-03-01

This study shows that ongoing electrical stimulation of the dopaminergic ventral midbrain can modify neuronal activity in the auditory cortex of awake primates for several seconds. This was reflected in a decrease of the spontaneous firing and in a bidirectional modification of the power of auditory evoked potentials. We consider that both effects are due to an increase in the dopamine tone in auditory cortex induced by the electrical stimulation. Thus, the dopaminergic ventral midbrain may contribute to the tonic activity in auditory cortex that has been proposed to be involved in associating events of auditory tasks (Brosch et al. Hear Res 271:66-73, 2011) and may modulate the signal-to-noise ratio of the responses to auditory stimuli.

Imprinting and Recalling Cortical Ensembles

PubMed Central

Carrillo-Reid, Luis; Yang, Weijian; Bando, Yuki; Peterka, Darcy S.; Yuste, Rafael

2017-01-01

Neuronal ensembles are coactive groups of neurons that may represent emergent building blocks of neural circuits. They could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations in visual cortex of awake mice generates artificially induced ensembles which recur spontaneously after being imprinted and do not disrupt preexistent ones. Moreover, imprinted ensembles can be recalled by single cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion. PMID:27516599

Interpretation of the function of the striate cortex

NASA Astrophysics Data System (ADS)

Garner, Bernardette M.; Paplinski, Andrew P.

2000-04-01

Biological neural networks do not require retraining every time objects move in the visual field. Conventional computer neural networks do not share this shift-invariance. The brain compensates for movements in the head, body, eyes and objects by allowing the sensory data to be tracked across the visual field. The neurons in the striate cortex respond to objects moving across the field of vision as is seen in many experiments. It is proposed, that the neurons in the striate cortex allow continuous angle changes needed to compensate for changes in orientation of the head, eyes and the motion of objects in the field of vision. It is hypothesized that the neurons in the striate cortex form a system that allows for the translation, some rotation and scaling of objects and provides a continuity of objects as they move relative to other objects. The neurons in the striate cortex respond to features which are fundamental to sight, such as orientation of lines, direction of motion, color and contrast. The neurons that respond to these features are arranged on the cortex in a way that depends on the features they are responding to and on the area of the retina from which they receive their inputs.

Visuomotor signals for reaching movements in the rostro-dorsal sector of the monkey thalamic reticular nucleus.

PubMed

Saga, Yosuke; Nakayama, Yoshihisa; Inoue, Ken-Ichi; Yamagata, Tomoko; Hashimoto, Masashi; Tremblay, Léon; Takada, Masahiko; Hoshi, Eiji

2017-05-01

The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. This unique connectivity suggests that the TRN plays a pivotal role in regulating information flow through the thalamus. Here, we analyzed the roles of TRN neurons in visually guided reaching movements. We first used retrograde transneuronal labeling with rabies virus, and showed that the rostro-dorsal sector of the TRN (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a visuomotor task. We found that neurons in the TRNrd and PMv showed visual-, set-, and movement-related activity modulation. These results indicate that the TRNrd, as well as the PMv, is involved in the reception of visual signals and in the preparation and execution of reaching movements. The fraction of neurons that were non-selective for the location of visual signals or the direction of reaching movements was greater in the TRNrd than in the PMv. Furthermore, the fraction of neurons whose activity increased from the baseline was greater in the TRNrd than in the PMv. The timing of activity modulation of visual-related and movement-related neurons was similar in TRNrd and PMv neurons. Overall, our data suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs that are predominantly devoid of spatial selectivity, and that these signals modulate how these nuclei engage in both sensory processing and motor output during visually guided reaching behavior. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Rotigotine, a dopamine receptor agonist, increased BDNF protein levels in the rat cortex and hippocampus.

PubMed

Adachi, Naoki; Yoshimura, Aya; Chiba, Shuichi; Ogawa, Shintaro; Kunugi, Hiroshi

2018-01-01

Brain-derived neurotrophic factor (BDNF) critically controls the fate and function of the neuronal network and has received much attention as a target of many brain diseases. Dopaminergic system dysfunction has also been implicated in a variety of neuropsychiatric diseases. Rotigotine, a non-ergot dopamine receptor agonist, is used in the treatment of Parkinson's disease and restless legs syndrome. To investigate the effects of rotigotine on neuronal functions both in vivo and in vitro, rats and primary cortical neurons were administered rotigotine, and the mRNA and protein expression levels of BDNF, its receptor TrkB and downstream signaling molecules, and synaptic proteins were determined. We found that BDNF protein was increased in the cortex and hippocampus of rats after 7days of rotigotine treatment. In contrast, BDNF mRNAs were reduced 6h after rotigotine treatment in cultured neurons presumably through the transient suppression of neuronal activity. We identified differential expression of D1, D2, and D3 receptors in the rat brain and cultured neurons. The observed increase in the expression of BDNF protein in the cortex and hippocampus after subchronic administration of rotigotine suggests that it may exert its medical effect in part through improving BDNF function in the brain. In addition, our results highlight the complex relationships between rotigotine and BDNF expression, which depend on the brain region, time course, and dose of the drug. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Neural coding in barrel cortex during whisker-guided locomotion

PubMed Central

Sofroniew, Nicholas James; Vlasov, Yurii A; Hires, Samuel Andrew; Freeman, Jeremy; Svoboda, Karel

2015-01-01

Animals seek out relevant information by moving through a dynamic world, but sensory systems are usually studied under highly constrained and passive conditions that may not probe important dimensions of the neural code. Here, we explored neural coding in the barrel cortex of head-fixed mice that tracked walls with their whiskers in tactile virtual reality. Optogenetic manipulations revealed that barrel cortex plays a role in wall-tracking. Closed-loop optogenetic control of layer 4 neurons can substitute for whisker-object contact to guide behavior resembling wall tracking. We measured neural activity using two-photon calcium imaging and extracellular recordings. Neurons were tuned to the distance between the animal snout and the contralateral wall, with monotonic, unimodal, and multimodal tuning curves. This rich representation of object location in the barrel cortex could not be predicted based on simple stimulus-response relationships involving individual whiskers and likely emerges within cortical circuits. DOI: http://dx.doi.org/10.7554/eLife.12559.001 PMID:26701910

Loss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the Developing Cerebral Cortex

PubMed Central

Laguesse, Sophie; Close, Pierre; Van Hees, Laura; Chariot, Alain; Malgrange, Brigitte; Nguyen, Laurent

2017-01-01

The Elongator complex is required for proper development of the cerebral cortex. Interfering with its activity in vivo delays the migration of postmitotic projection neurons, at least through a defective α-tubulin acetylation. However, this complex is already expressed by cortical progenitors where it may regulate the early steps of migration by targeting additional proteins. Here we report that connexin-43 (Cx43), which is strongly expressed by cortical progenitors and whose depletion impairs projection neuron migration, requires Elongator expression for its proper acetylation. Indeed, we show that Cx43 acetylation is reduced in the cortex of Elp3cKO embryos, as well as in a neuroblastoma cell line depleted of Elp1 expression, suggesting that Cx43 acetylation requires Elongator in different cellular contexts. Moreover, we show that histones deacetylase 6 (HDAC6) is a deacetylase of Cx43. Finally, we report that acetylation of Cx43 regulates its membrane distribution in apical progenitors of the cerebral cortex. PMID:28507509

Reward Systems in the Brain and Nutrition.

PubMed

Rolls, Edmund T

2016-07-17

The taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are combined by associative learning with olfactory and visual inputs for some neurons, and these neurons encode food reward value in that they respond to food only when hunger is present and in that activations correlate linearly with subjective pleasantness. Cognitive factors, including word-level descriptions and selective attention to affective value, modulate the representation of the reward value of taste, olfactory, and flavor stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex. These food reward representations are important in the control of appetite and food intake. Individual differences in reward representations may contribute to obesity, and there are age-related differences in these reward representations. Implications of how reward systems in the brain operate for understanding, preventing, and treating obesity are described.

Chronic multiunit recordings in behaving animals: advantages and limitations.

PubMed

Supèr, Hans; Roelfsema, Pieter R

2005-01-01

By simultaneous recording from neural responses at many different loci at the same time, we can understand the interaction between neurons, and thereby gain insight into the network properties of neural processing, instead of the functioning of individual neurons. Here we will discuss a method for recording in behaving animals that uses chronically implanted micro-electrodes that allow one to track neural responses over a long period of time. In a majority of cases, multiunit activity, which is the aggregate spiking activity of a number of neurons in the vicinity of an electrode tip, is recorded through these electrodes, and occasionally single neurons can be isolated. Here we compare the properties of multiunit responses to the responses of single neurons in the primary visual cortex. We also discuss the advantages and disadvantages of the multiunit signal as opposed to a signal of single neurons. We demonstrate that multiunit recording provides a reliable and useful technique in cases where the neurons at the electrodes have similar response properties. Multiunit recording is therefore especially valuable when task variables have an effect that is consistent across the population of neurons. In the primary visual cortex, this is the case for figure-ground segregation and visual attention. Multiunit recording also has clear advantages for cross-correlation analysis. We show that the cross-correlation function between multiunit signals gives a reliable estimate of the average single-unit cross-correlation function. By the use of multiunit recording, it becomes much easier to detect relatively weak interactions between neurons at different cortical locations.

Face-selective and auditory neurons in the primate orbitofrontal cortex.

PubMed

Rolls, Edmund T; Critchley, Hugo D; Browning, Andrew S; Inoue, Kazuo

2006-03-01

Neurons with responses selective for faces are described in the macaque orbitofrontal cortex. The neurons typically respond 2-13 times more to the best face than to the best non-face stimulus, and have response latencies which are typically in the range of 130-220 ms. Some of these face-selective neurons respond to identity, and others to facial expression. Some of the neurons do not have different responses to different views of a face, which is a useful property of neurons responding to face identity. Other neurons have view-dependent responses, and some respond to moving but not still heads. The neurons with face expression, face movement, or face view-dependent responses would all be useful as part of a system decoding and representing signals important in social interactions. The representation of face identity is also important in social interactions, for it provides some of the information needed in order to make different responses to different individuals. In addition, some orbitofrontal cortex neurons were shown to be tuned to auditory stimuli, including for some neurons, the sound of vocalizations. The findings are relevant to understanding the functions of the primate including human orbitofrontal cortex in normal behaviour, and to understanding the effects of damage to this region in humans.

Differences in reward processing between putative cell types in primate prefrontal cortex

PubMed Central

Fan, Hongwei; Wang, Rubin; Sakagami, Masamichi

2017-01-01

Single-unit studies in monkeys have demonstrated that neurons in the prefrontal cortex predict the reward type, reward amount or reward availability associated with a stimulus. To examine contributions of pyramidal cells and interneurons in reward processing, single-unit activity was extracellularly recorded in prefrontal cortices of four monkeys performing a reward prediction task. Based on their shapes of spike waveforms, prefrontal neurons were classified into broad-spike and narrow-spike units that represented putative pyramidal cells and interneurons, respectively. We mainly observed that narrow-spike neurons showed higher firing rates but less bursty discharges than did broad-spike neurons. Both narrow-spike and broad-spike cells selectively responded to the stimulus, reward and their interaction, and the proportions of each type of selective neurons were similar between the two cell classes. Moreover, the two types of cells displayed equal reliability of reward or stimulus discrimination. Furthermore, we found that broad-spike and narrow-spike cells showed distinct mechanisms for encoding reward or stimulus information. Broad-spike neurons raised their firing rate relative to the baseline rate to represent the preferred reward or stimulus information, whereas narrow-spike neurons inhibited their firing rate lower than the baseline rate to encode the non-preferred reward or stimulus information. Our results suggest that narrow-spike and broad-spike cells were equally involved in reward and stimulus processing in the prefrontal cortex. They utilized a binary strategy to complementarily represent reward or stimulus information, which was consistent with the task structure in which the monkeys were required to remember two reward conditions and two visual stimuli. PMID:29261734

Differences in reward processing between putative cell types in primate prefrontal cortex.

PubMed

Fan, Hongwei; Pan, Xiaochuan; Wang, Rubin; Sakagami, Masamichi

2017-01-01

Single-unit studies in monkeys have demonstrated that neurons in the prefrontal cortex predict the reward type, reward amount or reward availability associated with a stimulus. To examine contributions of pyramidal cells and interneurons in reward processing, single-unit activity was extracellularly recorded in prefrontal cortices of four monkeys performing a reward prediction task. Based on their shapes of spike waveforms, prefrontal neurons were classified into broad-spike and narrow-spike units that represented putative pyramidal cells and interneurons, respectively. We mainly observed that narrow-spike neurons showed higher firing rates but less bursty discharges than did broad-spike neurons. Both narrow-spike and broad-spike cells selectively responded to the stimulus, reward and their interaction, and the proportions of each type of selective neurons were similar between the two cell classes. Moreover, the two types of cells displayed equal reliability of reward or stimulus discrimination. Furthermore, we found that broad-spike and narrow-spike cells showed distinct mechanisms for encoding reward or stimulus information. Broad-spike neurons raised their firing rate relative to the baseline rate to represent the preferred reward or stimulus information, whereas narrow-spike neurons inhibited their firing rate lower than the baseline rate to encode the non-preferred reward or stimulus information. Our results suggest that narrow-spike and broad-spike cells were equally involved in reward and stimulus processing in the prefrontal cortex. They utilized a binary strategy to complementarily represent reward or stimulus information, which was consistent with the task structure in which the monkeys were required to remember two reward conditions and two visual stimuli.

Texture coarseness responsive neurons and their mapping in layer 2–3 of the rat barrel cortex in vivo

PubMed Central

Garion, Liora; Dubin, Uri; Rubin, Yoav; Khateb, Mohamed; Schiller, Yitzhak; Azouz, Rony; Schiller, Jackie

2014-01-01

Texture discrimination is a fundamental function of somatosensory systems, yet the manner by which texture is coded and spatially represented in the barrel cortex are largely unknown. Using in vivo two-photon calcium imaging in the rat barrel cortex during artificial whisking against different surface coarseness or controlled passive whisker vibrations simulating different coarseness, we show that layer 2–3 neurons within barrel boundaries differentially respond to specific texture coarsenesses, while only a minority of neurons responded monotonically with increased or decreased surface coarseness. Neurons with similar preferred texture coarseness were spatially clustered. Multi-contact single unit recordings showed a vertical columnar organization of texture coarseness preference in layer 2–3. These findings indicate that layer 2–3 neurons perform high hierarchical processing of tactile information, with surface coarseness embodied by distinct neuronal subpopulations that are spatially mapped onto the barrel cortex. DOI: http://dx.doi.org/10.7554/eLife.03405.001 PMID:25233151

Imprinting and recalling cortical ensembles.

PubMed

Carrillo-Reid, Luis; Yang, Weijian; Bando, Yuki; Peterka, Darcy S; Yuste, Rafael

2016-08-12

Neuronal ensembles are coactive groups of neurons that may represent building blocks of cortical circuits. These ensembles could be formed by Hebbian plasticity, whereby synapses between coactive neurons are strengthened. Here we report that repetitive activation with two-photon optogenetics of neuronal populations from ensembles in the visual cortex of awake mice builds neuronal ensembles that recur spontaneously after being imprinted and do not disrupt preexisting ones. Moreover, imprinted ensembles can be recalled by single- cell stimulation and remain coactive on consecutive days. Our results demonstrate the persistent reconfiguration of cortical circuits by two-photon optogenetics into neuronal ensembles that can perform pattern completion. Copyright © 2016, American Association for the Advancement of Science.

Altered olfactory processing of stress-related body odors and artificial odors in patients with panic disorder.

PubMed

Wintermann, Gloria-Beatrice; Donix, Markus; Joraschky, Peter; Gerber, Johannes; Petrowski, Katja

2013-01-01

Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Reference frames for spatial frequency in face representation differ in the temporal visual cortex and amygdala.

PubMed

Inagaki, Mikio; Fujita, Ichiro

2011-07-13

Social communication in nonhuman primates and humans is strongly affected by facial information from other individuals. Many cortical and subcortical brain areas are known to be involved in processing facial information. However, how the neural representation of faces differs across different brain areas remains unclear. Here, we demonstrate that the reference frame for spatial frequency (SF) tuning of face-responsive neurons differs in the temporal visual cortex and amygdala in monkeys. Consistent with psychophysical properties for face recognition, temporal cortex neurons were tuned to image-based SFs (cycles/image) and showed viewing distance-invariant representation of face patterns. On the other hand, many amygdala neurons were influenced by retina-based SFs (cycles/degree), a characteristic that is useful for social distance computation. The two brain areas also differed in the luminance contrast sensitivity of face-responsive neurons; amygdala neurons sharply reduced their responses to low luminance contrast images, while temporal cortex neurons maintained the level of their responses. From these results, we conclude that different types of visual processing in the temporal visual cortex and the amygdala contribute to the construction of the neural representations of faces.

Responses of neurons to extreme osmomechanical stress.

PubMed

Wan, X; Harris, J A; Morris, C E

1995-05-01

Neurons are often regarded as fragile cells, easily destroyed by mechanical and osmotic insult. The results presented here demonstrate that this perception needs revision. Using extreme osmotic swelling, we show that molluscan neurons are astonishingly robust. In distilled water, a heterogeneous population of Lymnaea stagnalis CNS neurons swelled to several times their initial volume, yet had a ST50 (survival time for 50% of cells) > 60 min. Cells that were initially bigger survived longer. On return to normal medium, survivors were able, over the next 24 hr, to rearborize. Reversible membrane capacitance changes corresponding to about 0.7 muF/cm2 of apparent surface area accompanied neuronal swelling and shrinking in hypo- and hyperosmotic solutions; reversible changes in cell surface area evidently contributed to the neurons' ability to accommodate hydrostatic pressures then recover. The reversible membrane area/capacitance changes were not dependent on extracellular Ca2+. Neurons were monitored for potassium currents during direct mechanical inflation and during osmotically driven inflation. The latter but not the former stimulus routinely elicited small potassium currents, suggesting that tension increases activate the currents only if additional disruption of the cortex has occurred. Under stress in distilled water, a third of the neurons displayed a quite unexpected behavior: prolonged writhing of peripheral regions of the soma. This suggested that a plasma membrane-linked contractile machinery (presumably actomyosin) might contribute to the neurons' mechano-osmotic robustness by restricting water influx. Consistent with this possibility, 1 mM N-ethyl-maleimide, which inhibits myosin ATPase, decreased the ST50 to 18 min, rendered the survival time independent of initial size, and abolished writhing activity. For neurons, active mechanical resistance of the submembranous cortex, along with the mechanical compliance supplied by insertion or eversion of membrane stores may account for the ability to withstand diverse mechanical stresses. Mechanical robustness such as that displayed here could be an asset during neuronal outgrowth or regeneration.

Double dissociation of value computations in orbitofrontal and anterior cingulate neurons

PubMed Central

Kennerley, Steven W.; Behrens, Timothy E. J.; Wallis, Jonathan D.

2011-01-01

Damage to prefrontal cortex (PFC) impairs decision-making, but the underlying value computations that might cause such impairments remain unclear. Here we report that value computations are doubly dissociable within PFC neurons. While many PFC neurons encoded chosen value, they used opponent encoding schemes such that averaging the neuronal population eliminated value coding. However, a special population of neurons in anterior cingulate cortex (ACC) - but not orbitofrontal cortex (OFC) - multiplex chosen value across decision parameters using a unified encoding scheme, and encoded reward prediction errors. In contrast, neurons in OFC - but not ACC - encoded chosen value relative to the recent history of choice values. Together, these results suggest complementary valuation processes across PFC areas: OFC neurons dynamically evaluate current choices relative to recent choice values, while ACC neurons encode choice predictions and prediction errors using a common valuation currency reflecting the integration of multiple decision parameters. PMID:22037498

Dementia of frontal lobe type and motor neuron disease. A Golgi study of the frontal cortex.

PubMed Central

Ferrer, I; Roig, C; Espino, A; Peiro, G; Matias Guiu, X

1991-01-01

Neuropathological findings in a 38 year old patient with dementia of frontal lobe type and motor neuron disease included pyramidal tracts, myelin pallor and neuron loss, gliosis and chromatolysis in the hypoglossal nucleus, together with frontal atrophy, neuron loss, gliosis and spongiosis in the upper cortical layers of the frontal (and temporal) lobes. Most remaining pyramidal and non-pyramidal neurons (multipolar, bitufted and bipolar cells) in the upper layers (layers II and III) of the frontal cortex (area B) had reduced dendritic arbors, proximal dendritic varicosities and amputation of dendrites as revealed in optimally stained rapid Golgi sections. Pyramidal cells in these layers also showed depletion of dendritic spines. Neurons in the inner layers were preserved. Loss of receptive surfaces in neurons of the upper cortical layers in the frontal cortex are indicative of neuronal disconnection, and are "hidden" contributory morphological substrates for the development of dementia. Images PMID:1744652

[Walking abnormalities in children].

PubMed

Segawa, Masaya

2010-11-01

Walking is a spontaneous movement termed locomotion that is promoted by activation of antigravity muscles by serotonergic (5HT) neurons. Development of antigravity activity follows 3 developmental epochs of the sleep-wake (S-W) cycle and is modulated by particular 5HT neurons in each epoch. Activation of antigravity activities occurs in the first epoch (around the age of 3 to 4 months) as restriction of atonia in rapid eye movement (REM) stage and development of circadian S-W cycle. These activities strengthen in the second epoch, with modulation of day-time sleep and induction of crawling around the age of 8 months and induction of walking by 1 year. Around the age of 1 year 6 months, absence of guarded walking and interlimb cordination is observed along with modulation of day-time sleep to once in the afternoon. Bipedal walking in upright position occurs in the third epoch, with development of a biphasic S-W cycle by the age of 4-5 years. Patients with infantile autism (IA), Rett syndrome (RTT), or Tourette syndrome (TS) show failure in the development of the first, second, or third epoch, respectively. Patients with IA fail to develop interlimb coordination; those with RTT, crawling and walking; and those with TS, walking in upright posture. Basic pathophysiology underlying these condition is failure in restricting atonia in REM stage; this induces dysfunction of the pedunculopontine nucleus and consequently dys- or hypofunction of the dopamine (DA) neurons. DA hypofunction in the developing brain, associated with compensatory upward regulation of the DA receptors causes psychobehavioral disorders in infancy (IA), failure in synaptogenesis in the frontal cortex and functional development of the motor and associate cortexes in late infancy through the basal ganglia (RTT), and failure in functional development of the prefrontal cortex through the basal ganglia (TS). Further, locomotion failure in early childhood causes failure in development of functional specialization of the cortex through the spinal stepping generator-fastigial nucleus-thalamus-cortex pathway. Early detection of locomotion failure and early adjustment of this condition through environmental factors can prevent the development of higher cortical dysfunction.

The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

PubMed

Mair, Robert G; Miller, Rikki L A; Wormwood, Benjamin A; Francoeur, Miranda J; Onos, Kristen D; Gibson, Brett M

2015-07-01

Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task. Copyright © 2015 Elsevier Ltd. All rights reserved.

A novel tetrode microdrive for simultaneous multi-neuron recording from different regions of primate brain.

PubMed

Santos, Lucas; Opris, Ioan; Fuqua, Joshua; Hampson, Robert E; Deadwyler, Sam A

2012-04-15

A unique custom-made tetrode microdrive for recording from large numbers of neurons in several areas of primate brain is described as a means for assessing simultaneous neural activity in cortical and subcortical structures in nonhuman primates (NHPs) performing behavioral tasks. The microdrive device utilizes tetrode technology with up to six ultra-thin microprobe guide tubes (0.1mm) that can be independently positioned, each containing reduced diameter tetrode and/or hexatrode microwires (0.02 mm) for recording and isolating single neuron activity. The microdrive device is mounted within the standard NHP cranial well and allows traversal of brain depths up to 40.0 mm. The advantages of this technology are demonstrated via simultaneously recorded large populations of neurons with tetrode type probes during task performance from a) primary motor cortex and deep brain structures (caudate-putamen and hippocampus) and b) multiple layers within the prefrontal cortex. The means to characterize interactions of well-isolated ensembles of neurons recorded simultaneously from different regions, as shown with this device, has not been previously available for application in primate brain. The device has extensive application to primate models for the detection and study of inoperative or maladaptive neural circuits related to human neurological disorders. Published by Elsevier B.V.

Soy isoflavones improve spatial delayed matching-to-place performance and reduce cholinergic neuron loss in elderly male rats.

PubMed

Lee, Yoon-Bok; Lee, Hyong Joo; Won, Moo Ho; Hwang, In Koo; Kang, Tae-Cheon; Lee, Jae-Yong; Nam, Sang-Yoon; Kim, Kang-Sung; Kim, Eugene; Cheon, Sang-Hee; Sohn, Heon-Soo

2004-07-01

To investigate the protective activity of soy isoflavones on neurons, the effects of isoflavones on cholinergic enzyme activity, immunoreactivities of cholinergic enzyme, and delayed matching-to-place (DMP) performance were measured in normal elderly rats. Male Sprague-Dawley rats (n = 48; 10 mo old) were assigned to 3 groups: CD (control diet), ISO 0.3 (0.3 g/kg soy isoflavones diet), and ISO 1.2 (1.2 g/kg soy isoflavones diet). After 16 wk of consuming these diets, choline acetyltransferase (ChAT) activity in the ISO 0.3 group was greater in cortex and basal forebrain (BF; P < 0.05) than in controls. In BF, ChAT activity was also significantly greater in the ISO 1.2 group than in control rats. Acetylcholine esterase (AChE) activity in the ISO 0.3 group was significantly inhibited in cortex, BF, and hippocampus and in the ISO 1.2 group in cortex and hippocampus. Choline acetyltransferase immunoreactivity (ChAT-IR) in the ISO 1.2 group was significantly greater than in controls in the medial septum area. ChAT-IR in the ISO 0.3 and ISO 1.2 groups was significantly higher than in the CD group in the hippocampus CA1 area. Spatial DMP performance by the ISO 0.3 group showed significantly shorter swimming time than by the CD group. These findings show that soy isoflavones can influence the brain cholinergic system and reduce age-related neuron loss and cognition decline in male rats.

Expression of Immediate-Early Genes in the Inferior Colliculus and Auditory Cortex in Salicylate-Induced Tinnitus in Rat

PubMed Central

Hu, S.S.; Mei, L.; Chen, J.Y.; Huang, Z.W.; Wu, H.

2014-01-01

Tinnitus could be associated with neuronal hyperactivity in the auditory center. As a neuronal activity marker, immediate-early gene (IEG) expression is considered part of a general neuronal response to natural stimuli. Some IEGs, especially the activity-dependent cytoskeletal protein (Arc) and the early growth response gene-1 (Egr-1), appear to be highly correlated with sensory-evoked neuronal activity. We hypothesize, therefore, an increase of Arc and Egr-1 will be observed in a tinnitus model. In our study, we used the gap prepulse inhibition of acoustic startle (GPIAS) paradigm to confirm that salicylate induces tinnitus-like behavior in rats. However, expression of the Arc gene and Egr-1 gene were decreased in the inferior colliculus (IC) and auditory cortex (AC), in contradiction of our hypothesis. Expression of N-methyl D-aspartate receptor subunit 2B (NR2B) was increased and all of these changes returned to normal 14 days after treatment with salicylate ceased. These data revealed long-time administration of salicylate induced tinnitus markedly but reversibly and caused neural plasticity changes in the IC and the AC. Decreased expression of Arc and Egr-1 might be involved with instability of synaptic plasticity in tinnitus. PMID:24704997

Egocentric and allocentric representations in auditory cortex

PubMed Central

Brimijoin, W. Owen; Bizley, Jennifer K.

2017-01-01

A key function of the brain is to provide a stable representation of an object’s location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system, and auditory cortex is necessary for sound localization. However, the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects; here we recorded spatial receptive fields in the auditory cortex of freely moving ferrets. We found that most spatially tuned neurons represented sound source location relative to the head across changes in head position and direction. In addition, we also recorded a small number of neurons in which sound location was represented in a world-centered coordinate frame. We used measurements of spatial tuning across changes in head position and direction to explore the influence of sound source distance and speed of head movement on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas, for both populations, modulation was stronger at faster movement speeds. Our findings suggest that early auditory cortex primarily represents sound source location relative to ourselves but that a minority of cells can represent sound location in the world independent of our own position. PMID:28617796

Large-scale oscillatory calcium waves in the immature cortex.

PubMed

Garaschuk, O; Linn, J; Eilers, J; Konnerth, A

2000-05-01

Two-photon imaging of large neuronal networks in cortical slices of newborn rats revealed synchronized oscillations in intracellular Ca2+ concentration. These spontaneous Ca2+ waves usually started in the posterior cortex and propagated slowly (2.1 mm per second) toward its anterior end. Ca2+ waves were associated with field-potential changes and required activation of AMPA and NMDA receptors. Although GABAA receptors were not involved in wave initiation, the developmental transition of GABAergic transmission from depolarizing to hyperpolarizing (around postnatal day 7) stopped the oscillatory activity. Thus we identified a type of large-scale Ca2+ wave that may regulate long-distance wiring in the immature cortex.

Localization of spontaneous bursting neuronal activity in the preterm human brain with simultaneous EEG-fMRI.

PubMed

Arichi, Tomoki; Whitehead, Kimberley; Barone, Giovanni; Pressler, Ronit; Padormo, Francesco; Edwards, A David; Fabrizi, Lorenzo

2017-09-12

Electroencephalographic recordings from the developing human brain are characterized by spontaneous neuronal bursts, the most common of which is the delta brush. Although similar events in animal models are known to occur in areas of immature cortex and drive their development, their origin in humans has not yet been identified. Here, we use simultaneous EEG-fMRI to localise the source of delta brush events in 10 preterm infants aged 32-36 postmenstrual weeks. The most frequent patterns were left and right posterior-temporal delta brushes which were associated in the left hemisphere with ipsilateral BOLD activation in the insula only; and in the right hemisphere in both the insular and temporal cortices. This direct measure of neural and hemodynamic activity shows that the insula, one of the most densely connected hubs in the developing cortex, is a major source of the transient bursting events that are critical for brain maturation.

Refinement of learned skilled movement representation in motor cortex deep output layer

PubMed Central

Li, Qian; Ko, Ho; Qian, Zhong-Ming; Yan, Leo Y. C.; Chan, Danny C. W.; Arbuthnott, Gordon; Ke, Ya; Yung, Wing-Ho

2017-01-01

The mechanisms underlying the emergence of learned motor skill representation in primary motor cortex (M1) are not well understood. Specifically, how motor representation in the deep output layer 5b (L5b) is shaped by motor learning remains virtually unknown. In rats undergoing motor skill training, we detect a subpopulation of task-recruited L5b neurons that not only become more movement-encoding, but their activities are also more structured and temporally aligned to motor execution with a timescale of refinement in tens-of-milliseconds. Field potentials evoked at L5b in vivo exhibit persistent long-term potentiation (LTP) that parallels motor performance. Intracortical dopamine denervation impairs motor learning, and disrupts the LTP profile as well as the emergent neurodynamical properties of task-recruited L5b neurons. Thus, dopamine-dependent recruitment of L5b neuronal ensembles via synaptic reorganization may allow the motor cortex to generate more temporally structured, movement-encoding output signal from M1 to downstream circuitry that drives increased uniformity and precision of movement during motor learning. PMID:28598433

The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Bo; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Science, Beijing 100101; Xia Jing

Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unitmore » responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.« less

Encoding changes in orbitofrontal cortex in reversal-impaired aged rats.

PubMed

Schoenbaum, Geoffrey; Setlow, Barry; Saddoris, Michael P; Gallagher, Michela

2006-03-01

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

PubMed

Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

2015-01-01

Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help researchers and clinicians to better understand the underlying modulation mechanisms of orofacial neuropathic pain and indicate a novel mechanism of ERK inhibitor-induced analgesia.

Cognitive-motor interactions of the basal ganglia in development

PubMed Central

Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

2014-01-01

Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

[Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

PubMed

Zhang, Li-quan; Xu, Jia-ni; Wang, Zhen-zhen; Zeng, Li-jun; Ye, Yi-lu; Zhang, Wei-ping; Wei, Er-qing; Zhang, Qi

2014-05-01

To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (Ps<0.05). However, minocycline significantly reduced the central distance and central time and increased the periphery time (Ps<0.05). Neurons were damaged in hippocampus, cortex and striatum after GCI, which manifested by decreased neurons and the most serious damage in hippocampal CA1 region. Minocycline significantly improved the neuron appearance and increased the neuron number in hippocampus and striatum (P<0.001 or P<0.05). Locomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.