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Sample records for neurons exert temporally

  1. Shape recognition and inferior temporal neurons.

    PubMed Central

    Schwartz, E L; Desimone, R; Albright, T D; Gross, C G

    1983-01-01

    Inferior temporal cortex plays an important role in shape recognition. To study the shape selectivity of single inferior temporal neurons, we recorded their responses to a set of shapes systematically varying in boundary curvature. Many inferior temporal neurons were selective for stimuli of specific boundary curvature and maintained this selectivity over changes in stimulus size or position. The method of describing boundary curvature was that of Fourier descriptors. PMID:6577453

  2. Spiking neuron model for temporal sequence recognition.

    PubMed

    Byrnes, Sean; Burkitt, Anthony N; Grayden, David B; Meffin, Hamish

    2010-01-01

    A biologically inspired neuronal network that stores and recognizes temporal sequences of symbols is described. Each symbol is represented by excitatory input to distinct groups of neurons (symbol pools). Unambiguous storage of multiple sequences with common subsequences is ensured by partitioning each symbol pool into subpools that respond only when the current symbol has been preceded by a particular sequence of symbols. We describe synaptic structure and neural dynamics that permit the selective activation of subpools by the correct sequence. Symbols may have varying durations of the order of hundreds of milliseconds. Physiologically plausible plasticity mechanisms operate on a time scale of tens of milliseconds; an interaction of the excitatory input with periodic global inhibition bridges this gap so that neural events representing successive symbols occur on this much faster timescale. The network is shown to store multiple overlapping sequences of events. It is robust to variation in symbol duration, it is scalable, and its performance degrades gracefully with perturbation of its parameters.

  3. Temporal correlations in neuronal avalanche occurrence

    PubMed Central

    Lombardi, F.; Herrmann, H. J.; Plenz, D.; de Arcangelis, L.

    2016-01-01

    Ongoing cortical activity consists of sequences of synchronized bursts, named neuronal avalanches, whose size and duration are power law distributed. These features have been observed in a variety of systems and conditions, at all spatial scales, supporting scale invariance, universality and therefore criticality. However, the mechanisms leading to burst triggering, as well as the relationship between bursts and quiescence, are still unclear. The analysis of temporal correlations constitutes a major step towards a deeper understanding of burst dynamics. Here, we investigate the relation between avalanche sizes and quiet times, as well as between sizes of consecutive avalanches recorded in cortex slice cultures. We show that quiet times depend on the size of preceding avalanches and, at the same time, influence the size of the following one. Moreover we evidence that sizes of consecutive avalanches are correlated. In particular, we show that an avalanche tends to be larger or smaller than the following one for short or long time separation, respectively. Our analysis represents the first attempt to provide a quantitative estimate of correlations between activity and quiescence in the framework of neuronal avalanches and will help to enlighten the mechanisms underlying spontaneous activity. PMID:27094323

  4. Temporal correlations in neuronal avalanche occurrence.

    PubMed

    Lombardi, F; Herrmann, H J; Plenz, D; de Arcangelis, L

    2016-04-20

    Ongoing cortical activity consists of sequences of synchronized bursts, named neuronal avalanches, whose size and duration are power law distributed. These features have been observed in a variety of systems and conditions, at all spatial scales, supporting scale invariance, universality and therefore criticality. However, the mechanisms leading to burst triggering, as well as the relationship between bursts and quiescence, are still unclear. The analysis of temporal correlations constitutes a major step towards a deeper understanding of burst dynamics. Here, we investigate the relation between avalanche sizes and quiet times, as well as between sizes of consecutive avalanches recorded in cortex slice cultures. We show that quiet times depend on the size of preceding avalanches and, at the same time, influence the size of the following one. Moreover we evidence that sizes of consecutive avalanches are correlated. In particular, we show that an avalanche tends to be larger or smaller than the following one for short or long time separation, respectively. Our analysis represents the first attempt to provide a quantitative estimate of correlations between activity and quiescence in the framework of neuronal avalanches and will help to enlighten the mechanisms underlying spontaneous activity.

  5. Copper nanoparticles exert size and concentration dependent toxicity on somatosensory neurons of rat

    PubMed Central

    PRABHU, BADANAVALU M.; ALI, SYED F.; MURDOCK, RICHARD C.; HUSSAIN, SABER M.; SRIVATSAN, MALATHI

    2010-01-01

    Metal nanoparticles, due to their unique properties and important applications in optical, magnetic, thermal, electrical, sensor devices and cosmetics, are beginning to be widely manufactured and used. This new and rapidly growing field of technology warrants a thorough examination of the material’s bio-compatibility and safety. Ultra-small particles may adversely affect living cells and organisms since they can easily penetrate the body through skin contact, inhalation and ingestion. Retrograde transport of copper nanoparticles from nerve endings on the skin can reach the somatosensory neurons in dorsal root ganglion (DRG). Since copper nanoparticles have industrial and healthcare applications, we determined the concentration and size-dependant effects of their exposure on survival of DRG neurons of rat in cell culture. The neurons were exposed to copper nanoparticles of increasing concentrations (10–100 μM) and sizes (40, 60 and 80 nm) for 24 h. Light microscopy, histochemical staining for copper, lactate dehydrogenase (LDH) assay for cell death, and MTS [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay for cell viability were performed to measure the resultant toxicity and cell survival. DRG neurons exposed to copper nanoparticles displayed vacuoles and detachment of some neurons from the substratum. Neurons also exhibited disrupted neurite network. LDH and MTS assays revealed that exposure to copper nanoparticles had significant toxic effect with all the sizes tested when compared to unexposed control cultures. Further analysis of the results showed that copper nanoparticles of smaller size and higher concentration exerted the maximum toxic effects. Rubeanic acid staining showed intracellular deposition of copper. These results demonstrate that copper nanoparticles are toxic in a size- and concentration-dependent manner to DRG neurons. PMID:20543894

  6. On the temporal organization of neuronal avalanches

    PubMed Central

    Lombardi, Fabrizio; Herrmann, Hans J.; Plenz, Dietmar; De Arcangelis, Lucilla

    2014-01-01

    Spontaneous activity of cortex in vitro and in vivo has been shown to organize as neuronal avalanches. Avalanches are cascades of neuronal activity that exhibit a power law in their size and duration distribution, typical features of balanced systems in a critical state. Recently it has been shown that the distribution of quiet times between consecutive avalanches in rat cortex slice cultures displays a non-monotonic behavior with a power law decay at short time scales. This behavior has been attributed to the slow alternation between up and down-states. Here we further characterize the avalanche process and investigate how the functional behavior of the quiet time distribution depends on the fine structure of avalanche sequences. By systematically removing smaller avalanches from the experimental time series we show that size and quiet times are correlated and highlight that avalanche occurrence exhibits the characteristic periodicity of θ and β/γ oscillations, which jointly emerge in most of the analyzed samples. Furthermore, our analysis indicates that smaller avalanches tend to be associated with faster β/γ oscillations, whereas larger ones are associated with slower θ and 1–2 Hz oscillations. In particular, large avalanches corresponding to θ cycles trigger cascades of smaller ones, which occur at β/γ frequency. This temporal structure follows closely the one of nested θ − β/γ oscillations. Finally we demonstrate that, because of the multiple time scales characterizing avalanche dynamics, the distributions of quiet times between avalanches larger than a certain size do not collapse onto a unique function when rescaled by the average occurrence rate. However, when considered separately in the up-state and in the down-state, these distributions are solely controlled by the respective average rate and two different unique function can be identified. PMID:25389393

  7. On the temporal organization of neuronal avalanches.

    PubMed

    Lombardi, Fabrizio; Herrmann, Hans J; Plenz, Dietmar; De Arcangelis, Lucilla

    2014-01-01

    Spontaneous activity of cortex in vitro and in vivo has been shown to organize as neuronal avalanches. Avalanches are cascades of neuronal activity that exhibit a power law in their size and duration distribution, typical features of balanced systems in a critical state. Recently it has been shown that the distribution of quiet times between consecutive avalanches in rat cortex slice cultures displays a non-monotonic behavior with a power law decay at short time scales. This behavior has been attributed to the slow alternation between up and down-states. Here we further characterize the avalanche process and investigate how the functional behavior of the quiet time distribution depends on the fine structure of avalanche sequences. By systematically removing smaller avalanches from the experimental time series we show that size and quiet times are correlated and highlight that avalanche occurrence exhibits the characteristic periodicity of θ and β/γ oscillations, which jointly emerge in most of the analyzed samples. Furthermore, our analysis indicates that smaller avalanches tend to be associated with faster β/γ oscillations, whereas larger ones are associated with slower θ and 1-2 Hz oscillations. In particular, large avalanches corresponding to θ cycles trigger cascades of smaller ones, which occur at β/γ frequency. This temporal structure follows closely the one of nested θ - β/γ oscillations. Finally we demonstrate that, because of the multiple time scales characterizing avalanche dynamics, the distributions of quiet times between avalanches larger than a certain size do not collapse onto a unique function when rescaled by the average occurrence rate. However, when considered separately in the up-state and in the down-state, these distributions are solely controlled by the respective average rate and two different unique function can be identified.

  8. Oleoylethanolamide exerts partial and dose-dependent neuroprotection of substantia nigra dopamine neurons.

    PubMed

    Galan-Rodriguez, B; Suarez, J; Gonzalez-Aparicio, R; Bermudez-Silva, F J; Maldonado, R; Robledo, P; Rodriguez de Fonseca, F; Fernandez-Espejo, E

    2009-03-01

    Oleoylethanolamide (OEA), agonist of nuclear PPAR-alpha receptors and antagonist of vanilloid TRPV1 receptors, has been reported to show cytoprotective properties. In this study, OEA-induced neuroprotection has been tested in vitro and in vivo models of 6-OHDA-induced degeneration of substantia nigra dopamine neurons. First, PPAR-alpha receptors were confirmed to be located in the nigrostriatal circuit, these receptors being expressed by dopamine neurons of the substantia nigra, and intrinsic neurons and fibers bundles of the dorsal striatum. In the substantia nigra, their location was confined to the ventral tier. The in vitro study showed that 1 microM OEA exerted a significantly neuroprotective effect on cultured nigral dopamine neurons, effects following U-shaped dose-response curves. Regarding the in vivo study, rats were locally injected with OEA into the right striatum and vehicle into the left striatum 30 min before 6-OHDA-induced striatal lesion. In the short term, signals of heme oxygenase-1 (oxidation marker, 24 and 48 h post-lesion) and OX6 (reactive microglia marker, 96 h post-lesion) were found to be significantly less intense in the striatum pretreated with 5 microM OEA. In the long term (1 month), reduction in striatal TH and synaptophysin was less intense whether the right striatum was pretreated with 5 microM OEA, and nigral TH+ neuron death was significantly reduced after pretreatment with 1 and 5 microM OEA. In vivo effects also followed U-shaped dose-response curves. In conclusion, OEA shows U-shaped partial and dose-dependent neuroprotective properties both in vitro and in vivo models of substantia nigra dopamine neuron degeneration. The occurrence of U-shaped dose-response relationships normally suggests toxicity due to high drug concentration or that opposing intracellular pathways are activated by different OEA doses.

  9. Ih-mediated depolarization enhances the temporal precision of neuronal integration

    PubMed Central

    Pavlov, Ivan; Scimemi, Annalisa; Savtchenko, Leonid; Kullmann, Dimitri M.; Walker, Matthew C.

    2011-01-01

    Feed-forward inhibition mediated by ionotropic GABAA receptors contributes to the temporal precision of neuronal signal integration. These receptors exert their inhibitory effect by shunting excitatory currents and by hyperpolarizing neurons. The relative roles of these mechanisms in neuronal computations are, however, incompletely understood. In this study, we show that by depolarizing the resting membrane potential relative to the reversal potential for GABAA receptors, the hyperpolarization-activated mixed cation current (Ih) maintains a voltage gradient for fast synaptic inhibition in hippocampal pyramidal cells. Pharmacological or genetic ablation of Ih broadens the depolarizing phase of afferent synaptic waveforms by hyperpolarizing the resting membrane potential. This increases the integration time window for action potential generation. These results indicate that the hyperpolarizing component of GABAA receptor-mediated inhibition has an important role in maintaining the temporal fidelity of coincidence detection and suggest a previously unrecognized mechanism by which Ih modulates information processing in the hippocampus. PMID:21326231

  10. Temporal coherence structure rapidly shapes neuronal interactions

    PubMed Central

    Lu, Kai; Xu, Yanbo; Yin, Pingbo; Oxenham, Andrew J.; Fritz, Jonathan B.; Shamma, Shihab A.

    2017-01-01

    Perception of segregated sources is essential in navigating cluttered acoustic environments. A basic mechanism to implement this process is the temporal coherence principle. It postulates that a signal is perceived as emitted from a single source only when all of its features are temporally modulated coherently, causing them to bind perceptually. Here we report on neural correlates of this process as rapidly reshaped interactions in primary auditory cortex, measured in three different ways: as changes in response rates, as adaptations of spectrotemporal receptive fields following stimulation by temporally coherent and incoherent tone sequences, and as changes in spiking correlations during the tone sequences. Responses, sensitivity and presumed connectivity were rapidly enhanced by synchronous stimuli, and suppressed by alternating (asynchronous) sounds, but only when the animals engaged in task performance and were attentive to the stimuli. Temporal coherence and attention are therefore both important factors in auditory scene analysis. PMID:28054545

  11. Temporal structure of neuronal population oscillations with empirical model decomposition

    NASA Astrophysics Data System (ADS)

    Li, Xiaoli

    2006-08-01

    Frequency analysis of neuronal oscillation is very important for understanding the neural information processing and mechanism of disorder in the brain. This Letter addresses a new method to analyze the neuronal population oscillations with empirical mode decomposition (EMD). Following EMD of neuronal oscillation, a series of intrinsic mode functions (IMFs) are obtained, then Hilbert transform of IMFs can be used to extract the instantaneous time frequency structure of neuronal oscillation. The method is applied to analyze the neuronal oscillation in the hippocampus of epileptic rats in vivo, the results show the neuronal oscillations have different descriptions during the pre-ictal, seizure onset and ictal periods of the epileptic EEG at the different frequency band. This new method is very helpful to provide a view for the temporal structure of neural oscillation.

  12. Prefrontal neuronal assemblies temporally control fear behaviour.

    PubMed

    Dejean, Cyril; Courtin, Julien; Karalis, Nikolaos; Chaudun, Fabrice; Wurtz, Hélène; Bienvenu, Thomas C M; Herry, Cyril

    2016-07-21

    Precise spike timing through the coordination and synchronization of neuronal assemblies is an efficient and flexible coding mechanism for sensory and cognitive processing. In cortical and subcortical areas, the formation of cell assemblies critically depends on neuronal oscillations, which can precisely control the timing of spiking activity. Whereas this form of coding has been described for sensory processing and spatial learning, its role in encoding emotional behaviour remains unknown. Fear behaviour relies on the activation of distributed structures, among which the dorsal medial prefrontal cortex (dmPFC) is known to be critical for fear memory expression. In the dmPFC, the phasic activation of neurons to threat-predicting cues, a spike-rate coding mechanism, correlates with conditioned fear responses and supports the discrimination between aversive and neutral stimuli. However, this mechanism does not account for freezing observed outside stimuli presentations, and the contribution of a general spike-time coding mechanism for freezing in the dmPFC remains to be established. Here we use a combination of single-unit and local field potential recordings along with optogenetic manipulations to show that, in the dmPFC, expression of conditioned fear is causally related to the organization of neurons into functional assemblies. During fear behaviour, the development of 4 Hz oscillations coincides with the activation of assemblies nested in the ascending phase of the oscillation. The selective optogenetic inhibition of dmPFC neurons during the ascending or descending phases of this oscillation blocks and promotes conditioned fear responses, respectively. These results identify a novel phase-specific coding mechanism, which dynamically regulates the development of dmPFC assemblies to control the precise timing of fear responses.

  13. Flagellar biosynthesis exerts temporal regulation of secretion of specific Campylobacter jejuni colonization and virulence determinants.

    PubMed

    Barrero-Tobon, Angelica M; Hendrixson, David R

    2014-09-01

    The Campylobacter jejuni flagellum exports both proteins that form the flagellar organelle for swimming motility and colonization and virulence factors that promote commensal colonization of the avian intestinal tract or invasion of human intestinal cells respectively. We explored how the C. jejuni flagellum is a versatile secretory organelle by examining molecular determinants that allow colonization and virulence factors to exploit the flagellum for their own secretion. Flagellar biogenesis was observed to exert temporal control of secretion of these proteins, indicating that a bolus of secretion of colonization and virulence factors occurs during hook biogenesis with filament polymerization itself reducing secretion of these factors. Furthermore, we found that intramolecular and intermolecular requirements for flagellar-dependent secretion of these proteins were most reminiscent to those for flagellin secretion. Importantly, we discovered that secretion of one colonization and virulence factor, CiaI, was not required for invasion of human colonic cells, which counters previous hypotheses for how this protein functions during invasion. Instead, secretion of CiaI was essential for C. jejuni to facilitate commensal colonization of the natural avian host. Our work provides insight into the versatility of the bacterial flagellum as a secretory machine that can export proteins promoting diverse biological processes.

  14. Neuronal oscillations as a mechanistic substrate of auditory temporal prediction

    PubMed Central

    Morillon, Benjamin; Schroeder, Charles E.

    2014-01-01

    Neuronal oscillations are comprised of rhythmic fluctuations of excitability that are synchronized in ensembles of neurons and thus function as temporal filters that dynamically organize sensory processing. When perception relies on anticipatory mechanisms, ongoing oscillations also provide a neurophysiological substrate for temporal prediction. In this article we review evidence for this account with a focus on auditory perception. We argue that such “oscillatory temporal predictions” can selectively amplify neuronal sensitivity to inputs that occur in a predicted, task-relevant rhythm and optimize temporal selection. We elaborate this argument for a prototypic example, speech processing, where information is present at multiple time scales, with delta, theta, and low-gamma oscillations being specifically and simultaneously engaged, enabling multiplexing. We then consider the origin of temporal predictions, specifically the idea that the motor system is involved in the generation of such prior information. Finally, we place temporal predictions in the general context of internal models, discussing how they interact with feature-based or spatial predictions. We propose that complementary predictions interact synergistically according to a dominance hierarchy, shaping perception in the form of a multidimensional filter mechanism. PMID:25773613

  15. Neuronal oscillations as a mechanistic substrate of auditory temporal prediction.

    PubMed

    Morillon, Benjamin; Schroeder, Charles E

    2015-03-01

    Neuronal oscillations are comprised of rhythmic fluctuations of excitability that are synchronized in ensembles of neurons and thus function as temporal filters that dynamically organize sensory processing. When perception relies on anticipatory mechanisms, ongoing oscillations also provide a neurophysiological substrate for temporal prediction. In this article, we review evidence for this account with a focus on auditory perception. We argue that such "oscillatory temporal predictions" can selectively amplify neuronal sensitivity to inputs that occur in a predicted, task-relevant rhythm and optimize temporal selection. We elaborate this argument for a prototypic example, speech processing, where information is present at multiple time scales, with delta, theta, and low-gamma oscillations being specifically and simultaneously engaged, enabling multiplexing. We then consider the origin of temporal predictions, specifically the idea that the motor system is involved in the generation of such prior information. Finally, we place temporal predictions in the general context of internal models, discussing how they interact with feature-based or spatial predictions. We propose that complementary predictions interact synergistically according to a dominance hierarchy, shaping perception in the form of a multidimensional filter mechanism.

  16. Kinin-B2 Receptor Exerted Neuroprotection After Diisopropylfluorophosphate-induced Neuronal Damage

    PubMed Central

    Torres-Rivera, Wilmarie; Pérez, Dinely; Park, Keon-Young; Carrasco, Marimée; Platt, Manu O.; Eterović, Vesna A.; Ferchmin, Pedro A.; Ulrich, Henning; Martins, Antonio H.

    2013-01-01

    The kinin-B2 receptor (B2BKR) activated by its endogenous ligand bradykinin participates in various metabolic processes including control of arterial pressure and inflammation. Recently, functions for this receptor in brain development and protection against glutamate-provoked excitotoxicity have been proposed. Here, we report neuroprotective properties for bradykinin against organophosphate poisoning using acute hippocampal slices as an in vitro model. Following slice perfusion for 10 min with diisopropylfluorophosphate (DFP) to initiate the noxious stimulus, responses of pyramidal neurons upon an electric impulse were reduced to less than 30 % of control amplitudes. Effects on synaptic-elicited population spikes were reverted when preparations had been exposed to bradykinin 30 min after challenging with DFP. Accordingly, bradykinin-induced population spike recovery was abolished by HOE-140, a B2BKR antagonist. However, the kinin-B1 receptor (B1BKR) agonist Lys-des-Arg9-bradykinin, inducing phosphorylation of MEK/MAPK and cell death, abolished bradykinin-mediated neuroprotection, an effect, which was reverted by the ERK inhibitor PD98059. In agreement with pivotal B1BKR functions in this process, antagonism of endogenous B1BKR activity alone was enough for restoring population spike activity. On the other hand pralidoxime, an oxime, reactivating AChE after organophosphate poisoning, induced population spike recovery after DFP exposure in the presence of bradykinin and Lys-des-Arg9-bradykinin. Lys-des-Arg9-bradykinin did not revert protection exerted by pralidoxime, however when instead bradykinin and Ly-des-Arg9-bradykinin were superfused together, recovery of population spikes diminished. These findings again confirm the neuroprotective feature of bradykinin, which is, diminished by its endogenous metabolites, stimulating the B1BKR, providing a novel understanding of physiological roles of these receptors. PMID:23735753

  17. Role of Temporal Processing Stages by Inferior Temporal Neurons in Facial Recognition

    PubMed Central

    Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Kawano, Kenji

    2011-01-01

    In this review, we focus on the role of temporal stages of encoded facial information in the visual system, which might enable the efficient determination of species, identity, and expression. Facial recognition is an important function of our brain and is known to be processed in the ventral visual pathway, where visual signals are processed through areas V1, V2, V4, and the inferior temporal (IT) cortex. In the IT cortex, neurons show selective responses to complex visual images such as faces, and at each stage along the pathway the stimulus selectivity of the neural responses becomes sharper, particularly in the later portion of the responses. In the IT cortex of the monkey, facial information is represented by different temporal stages of neural responses, as shown in our previous study: the initial transient response of face-responsive neurons represents information about global categories, i.e., human vs. monkey vs. simple shapes, whilst the later portion of these responses represents information about detailed facial categories, i.e., expression and/or identity. This suggests that the temporal stages of the neuronal firing pattern play an important role in the coding of visual stimuli, including faces. This type of coding may be a plausible mechanism underlying the temporal dynamics of recognition, including the process of detection/categorization followed by the identification of objects. Recent single-unit studies in monkeys have also provided evidence consistent with the important role of the temporal stages of encoded facial information. For example, view-invariant facial identity information is represented in the response at a later period within a region of face-selective neurons. Consistent with these findings, temporally modulated neural activity has also been observed in human studies. These results suggest a close correlation between the temporal processing stages of facial information by IT neurons and the temporal dynamics of face recognition

  18. [Temporal perception and organisation, neuronal synchronisation and schizophrenia].

    PubMed

    Braus, D F

    2002-11-01

    Basic perceptual or motor skills involving the central nervous system as well as the subjective present require the orderly temporal organization of internal and external information. Current research in schizophrenia increasingly centers on the accompanying neurocognitive deficits with frequent reports of altered temporal processes. There has been, however, less explicit research on the basic phenomenon of temporal order. Using concrete operationalized neuropsychological procedures the present study addressed the question whether chronic schizophrenic patients (28 medicated as well as 7 unmedicated) differ in their ability to correctly judge the temporal order of visual or acoustic stimuli when compared with a healthy control group (n = 26). Within this context we found a significant impairment in basal temporal perception among patients. Moderating variables such as medication, attention deficits or the effects of motivation as an essential explanatory factor for this finding could be excluded by statistical analysis. Instead, our findings point to a fundamental disturbance in the temporal coordination of neuronal network functions in association with schizophrenic psychoses. Within this context neurophysiological, neurochemical, neuroanatomical and neuropsychological overlapping of schizophrenia and temporal perception are being presented along with a discussion of the hypothesis that disturbances in neuronal synchronization and in timing processes at different levels are of essence and a possible underlying substrate in the schizophrenic spectrum.

  19. Temporal pairwise spike correlations fully capture single-neuron information

    PubMed Central

    Dettner, Amadeus; Münzberg, Sabrina; Tchumatchenko, Tatjana

    2016-01-01

    To crack the neural code and read out the information neural spikes convey, it is essential to understand how the information is coded and how much of it is available for decoding. To this end, it is indispensable to derive from first principles a minimal set of spike features containing the complete information content of a neuron. Here we present such a complete set of coding features. We show that temporal pairwise spike correlations fully determine the information conveyed by a single spiking neuron with finite temporal memory and stationary spike statistics. We reveal that interspike interval temporal correlations, which are often neglected, can significantly change the total information. Our findings provide a conceptual link between numerous disparate observations and recommend shifting the focus of future studies from addressing firing rates to addressing pairwise spike correlation functions as the primary determinants of neural information. PMID:27976717

  20. Temporal characteristics of gustatory responses in rat parabrachial neurons vary by stimulus and chemosensitive neuron type.

    PubMed

    Geran, Laura; Travers, Susan

    2013-01-01

    It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of "sweet" (sucrose), "salty" (NaCl), "sour" (citric acid), and "bitter" (quinine and cycloheximide) stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500 ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H) afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H) in neurons that responded optimally to bitter stimuli (B-best). Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs.

  1. Temporal integration by stochastic recurrent network dynamics with bimodal neurons.

    PubMed

    Okamoto, Hiroshi; Isomura, Yoshikazu; Takada, Masahiko; Fukai, Tomoki

    2007-06-01

    Temporal integration of externally or internally driven information is required for a variety of cognitive processes. This computation is generally linked with graded rate changes in cortical neurons, which typically appear during a delay period of cognitive task in the prefrontal and other cortical areas. Here, we present a neural network model to produce graded (climbing or descending) neuronal activity. Model neurons are interconnected randomly by AMPA-receptor-mediated fast excitatory synapses and are subject to noisy background excitatory and inhibitory synaptic inputs. In each neuron, a prolonged afterdepolarizing potential follows every spike generation. Then, driven by an external input, the individual neurons display bimodal rate changes between a baseline state and an elevated firing state, with the latter being sustained by regenerated afterdepolarizing potentials. When the variance of background input and the uniform weight of recurrent synapses are adequately tuned, we show that stochastic noise and reverberating synaptic input organize these bimodal changes into a sequence that exhibits graded population activity with a nearly constant slope. To test the validity of the proposed mechanism, we analyzed the graded activity of anterior cingulate cortex neurons in monkeys performing delayed conditional Go/No-go discrimination tasks. The delay-period activities of cingulate neurons exhibited bimodal activity patterns and trial-to-trial variability that are similar to those predicted by the proposed model.

  2. Temporally selective processing of communication signals by auditory midbrain neurons

    PubMed Central

    Christensen-Dalsgaard, Jakob; Kelley, Darcy B.

    2011-01-01

    Perception of the temporal structure of acoustic signals contributes critically to vocal signaling. In the aquatic clawed frog Xenopus laevis, calls differ primarily in the temporal parameter of click rate, which conveys sexual identity and reproductive state. We show here that an ensemble of auditory neurons in the laminar nucleus of the torus semicircularis (TS) of X. laevis specializes in encoding vocalization click rates. We recorded single TS units while pure tones, natural calls, and synthetic clicks were presented directly to the tympanum via a vibration-stimulation probe. Synthesized click rates ranged from 4 to 50 Hz, the rate at which the clicks begin to overlap. Frequency selectivity and temporal processing were characterized using response-intensity curves, temporal-discharge patterns, and autocorrelations of reduplicated responses to click trains. Characteristic frequencies ranged from 140 to 3,250 Hz, with minimum thresholds of −90 dB re 1 mm/s at 500 Hz and −76 dB at 1,100 Hz near the dominant frequency of female clicks. Unlike units in the auditory nerve and dorsal medullary nucleus, most toral units respond selectively to the behaviorally relevant temporal feature of the rate of clicks in calls. The majority of neurons (85%) were selective for click rates, and this selectivity remained unchanged over sound levels 10 to 20 dB above threshold. Selective neurons give phasic, tonic, or adapting responses to tone bursts and click trains. Some algorithms that could compute temporally selective receptive fields are described. PMID:21289132

  3. Spatio-temporal credit assignment in neuronal population learning.

    PubMed

    Friedrich, Johannes; Urbanczik, Robert; Senn, Walter

    2011-06-01

    In learning from trial and error, animals need to relate behavioral decisions to environmental reinforcement even though it may be difficult to assign credit to a particular decision when outcomes are uncertain or subject to delays. When considering the biophysical basis of learning, the credit-assignment problem is compounded because the behavioral decisions themselves result from the spatio-temporal aggregation of many synaptic releases. We present a model of plasticity induction for reinforcement learning in a population of leaky integrate and fire neurons which is based on a cascade of synaptic memory traces. Each synaptic cascade correlates presynaptic input first with postsynaptic events, next with the behavioral decisions and finally with external reinforcement. For operant conditioning, learning succeeds even when reinforcement is delivered with a delay so large that temporal contiguity between decision and pertinent reward is lost due to intervening decisions which are themselves subject to delayed reinforcement. This shows that the model provides a viable mechanism for temporal credit assignment. Further, learning speeds up with increasing population size, so the plasticity cascade simultaneously addresses the spatial problem of assigning credit to synapses in different population neurons. Simulations on other tasks, such as sequential decision making, serve to contrast the performance of the proposed scheme to that of temporal difference-based learning. We argue that, due to their comparative robustness, synaptic plasticity cascades are attractive basic models of reinforcement learning in the brain.

  4. Human temporal cortical single neuron activity during working memory maintenance.

    PubMed

    Zamora, Leona; Corina, David; Ojemann, George

    2016-06-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  5. A neuronal learning rule for sub-millisecond temporal coding.

    PubMed

    Gerstner, W; Kempter, R; van Hemmen, J L; Wagner, H

    1996-09-05

    A paradox that exists in auditory and electrosensory neural systems is that they encode behaviorally relevant signals in the range of a few microseconds with neurons that are at least one order of magnitude slower. The importance of temporal coding in neural information processing is not clear yet. A central question is whether neuronal firing can be more precise than the time constants of the neuronal processes involved. Here we address this problem using the auditory system of the barn owl as an example. We present a modelling study based on computer simulations of a neuron in the laminar nucleus. Three observations explain the paradox. First, spiking of an 'integrate-and-fire' neuron driven by excitatory postsynaptic potentials with a width at half-maximum height of 250 micros, has an accuracy of 25 micros if the presynaptic signals arrive coherently. Second, the necessary degree of coherence in the signal arrival times can be attained during ontogenetic development by virtue of an unsupervised hebbian learning rule. Learning selects connections with matching delays from a broad distribution of axons with random delays. Third, the learning rule also selects the correct delays from two independent groups of inputs, for example, from the left and right ear.

  6. A neuronal learning rule for sub-millisecond temporal coding

    NASA Astrophysics Data System (ADS)

    Gerstner, Wulfram; Kempter, Richard; van Hemmen, J. Leo; Wagner, Hermann

    1996-09-01

    A PARADOX that exists in auditory and electrosensory neural systems1,2 is that they encode behaviourally relevant signals in the range of a few microseconds with neurons that are at least one order of magnitude slower. The importance of temporal coding in neural information processing is not clear yet3-8. A central question is whether neuronal firing can be more precise than the time constants of the neuronal processes involved9. Here we address this problem using the auditory system of the barn owl as an example. We present a modelling study based on computer simulations of a neuron in the laminar nucleus. Three observations explain the paradox. First, spiking of an 'integrate-and-fire' neuron driven by excitatory postsynaptic potentials with a width at half-maximum height of 250 μs, has an accuracy of 25 μs if the presynaptic signals arrive coherently. Second, the necessary degree of coherence in the signal arrival times can be attained during ontogenetic development by virtue of an unsupervised hebbian learning rule. Learning selects connections with matching delays from a broad distribution of axons with random delays. Third, the learning rule also selects the correct delays from two independent groups of inputs, for example, from the left and right ear.

  7. On-line, voluntary control of human temporal lobe neurons.

    PubMed

    Cerf, Moran; Thiruvengadam, Nikhil; Mormann, Florian; Kraskov, Alexander; Quiroga, Rodrigo Quian; Koch, Christof; Fried, Itzhak

    2010-10-28

    Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display.

  8. Human Temporal Cortical Single Neuron Activity during Language: A Review

    PubMed Central

    Ojemann, George A.

    2013-01-01

    Findings from recordings of human temporal cortical single neuron activity during several measures of language, including object naming and word reading are reviewed and related to changes in activity in the same neurons during recent verbal memory and verbal associative learning measures, in studies conducted during awake neurosurgery for the treatment of epilepsy. The proportion of neurons changing activity with language tasks was similar in either hemisphere. Dominant hemisphere activity was characterized by relative inhibition, some of which occurred during overt speech, possibly to block perception of one’s own voice. However, the majority seems to represent a dynamic network becoming active with verbal memory encoding and especially verbal learning, but inhibited during performance of overlearned language tasks. Individual neurons are involved in different networks for different aspects of language, including naming or reading and naming in different languages. The majority of the changes in activity were tonic sustained shifts in firing. Patterned phasic activity for specific language items was very infrequently recorded. Human single neuron recordings provide a unique perspective on the biologic substrate for language, for these findings are in contrast to many of the findings from other techniques for investigating this. PMID:24961418

  9. On-line, voluntary control of human temporal lobe neurons

    PubMed Central

    Cerf, Moran; Thiruvengadam, Nikhil; Mormann, Florian; Kraskov, Alexander; Quiroga, Rodrigo Quian; Koch, Christof; Fried, Itzhak

    2010-01-01

    Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition1–4. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons5–9, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display. PMID:20981100

  10. Quercetin Exerts Differential Neuroprotective Effects Against H2O2 and Aβ Aggregates in Hippocampal Neurons: the Role of Mitochondria.

    PubMed

    Godoy, Juan A; Lindsay, Carolina B; Quintanilla, Rodrigo A; Carvajal, Francisco J; Cerpa, Waldo; Inestrosa, Nibaldo C

    2016-10-28

    Amyloid-β peptide (Aβ) is one of the major players in the pathogenesis of Alzheimer's disease (AD). Despite numerous studies, the mechanisms by which Aβ induces neurodegeneration are not completely understood. Oxidative stress is considered a major contributor to the pathogenesis of AD, and accumulating evidence indicates that high levels of reactive oxygen species (ROS) are involved in Aβ-induced neurodegeneration. Moreover, Aβ can induce the deregulation of calcium homeostasis, which also affects mitochondrial function and triggers neuronal cell death. In the present study, we analyzed the effects of quercetin, a plant flavonoid with antioxidant properties, on oxidative stress- and Aβ-induced degeneration. Our results indicate that quercetin efficiently protected against H2O2-induced neuronal toxicity; however, this protection was only partial in rat hippocampal neurons that were treated with Aβ. Treatment with quercetin decreased ROS levels, recovered the normal morphology of mitochondria, and prevented mitochondrial dysfunction in neurons that were treated with H2O2. By contrast, quercetin treatment partially rescued hippocampal neurons from Aβ-induced mitochondrial injury. Most importantly, quercetin treatment prevented the toxic effects that are induced by H2O2 in hippocampal neurons and, to a lesser extent, the Aβ-induced toxicity that is associated with the superoxide anion, which is a precursor of ROS production in mitochondria. Collectively, these results indicate that quercetin exerts differential effects on the prevention of H2O2- and Aβ-induced neurotoxicity in hippocampal neurons and may be a powerful tool for dissecting the molecular mechanisms underlying Aβ neurotoxicity.

  11. Repeated restraint stress exerts different impact on structure of neurons in the lateral and basal nuclei of the amygdala

    PubMed Central

    Padival, Mallika A.; Blume, Shannon R.; Rosenkranz, J. Amiel

    2013-01-01

    Chronic stress exacerbates and can induce symptoms of depression and anxiety disorders. Chronic stress causes amygdala hyperactivity, which may contribute to these detrimental effects. One potential mechanism for amygdala hyperactivity is an increase of excitatory drive after stress. Excitatory inputs to the amygdala predominantly synapse upon dendritic spines, and repeated stress has been demonstrated to increase dendritic spines in the basolateral amygdala (BLA). However, the BLA is comprised of several nuclei, including the lateral nucleus (LAT) and the basal nucleus (BA), which exert functionally distinct roles in amygdala-dependent behaviors. Furthermore, while an increase of dendritic spines can impart significant functional ramifications, a shift of spine distribution can also exert significant impact. However, differences in the effects of repeated stress on LAT and BA have not been examined, nor differential effects on spine distribution. This study examined the effects of repeated restraint stress on dendritic structure of principal neurons from the LAT and BA in Golgi-stained tissue. This study found that repeated stress increased spine number in LAT and BA, but in very distinct patterns, with proximal increases in LAT neurons and non-proximal increases in BA neurons. Furthermore, repeated stress increased dendritic length in the BA, but not the LAT, leading to a global change of spine density in BA, but a focal change in LAT. These distinct effects of repeated stress in the LAT and BA may exert significant functional effects on fear behavior, and may underlie differences in the effects of repeated stress on acquisition, contextual modulation and extinction of fear behavior. PMID:23660193

  12. Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

    PubMed Central

    Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

    2011-01-01

    Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

  13. Intranasally Administered Neuropeptide S (NPS) Exerts Anxiolytic Effects Following Internalization Into NPS Receptor-Expressing Neurons

    PubMed Central

    Ionescu, Irina A; Dine, Julien; Yen, Yi-Chun; Buell, Dominik R; Herrmann, Leonie; Holsboer, Florian; Eder, Matthias; Landgraf, Rainer; Schmidt, Ulrike

    2012-01-01

    Experiments in rodents revealed neuropeptide S (NPS) to constitute a potential novel treatment option for anxiety diseases such as panic and post-traumatic stress disorder. However, both its cerebral target sites and the molecular underpinnings of NPS-mediated effects still remain elusive. By administration of fluorophore-conjugated NPS, we pinpointed NPS target neurons in distinct regions throughout the entire brain. We demonstrated their functional relevance in the hippocampus. In the CA1 region, NPS modulates synaptic transmission and plasticity. NPS is taken up into NPS receptor-expressing neurons by internalization of the receptor–ligand complex as we confirmed by subsequent cell culture studies. Furthermore, we tracked internalization of intranasally applied NPS at the single-neuron level and additionally demonstrate that it is delivered into the mouse brain without losing its anxiolytic properties. Finally, we show that NPS differentially modulates the expression of proteins of the glutamatergic system involved inter alia in synaptic plasticity. These results not only enlighten the path of NPS in the brain, but also establish a non-invasive method for NPS administration in mice, thus strongly encouraging translation into a novel therapeutic approach for pathological anxiety in humans. PMID:22278093

  14. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells

    PubMed Central

    Basile, John R.; Binmadi, Nada O.; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks. PMID:23675320

  15. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells.

    PubMed

    Basile, John R; Binmadi, Nada O; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  16. Temporally Unpredictable Sounds Exert a Context-Dependent Influence on Evaluation of Unrelated Images

    PubMed Central

    Bach, Dominik R.; Seifritz, Erich; Dolan, Raymond J.

    2015-01-01

    Temporally unpredictable stimuli influence murine and human behaviour, as previously demonstrated for sequences of simple sounds with regular or irregular onset. It is unknown whether this influence is mediated by an evaluation of the unpredictable sound sequences themselves, or by an interaction with task context. Here, we find that humans evaluate unrelated neutral pictures as more negative when these are presented together with a temporally unpredictable sound sequence, compared to a predictable sequence. The same is observed for evaluation of neutral, angry and fearful face photographs. Control experiments suggest this effect is specific to interspersed presentation of negative and neutral visual stimuli. Unpredictable sounds presented on their own were evaluated as more activating, but not more aversive, and were preferred over predictable sounds. When presented alone, these sound sequences also did not elicit tonic autonomic arousal or negative mood change. We discuss how these findings might account for previous data on the effects of unpredictable sounds, in humans and rodents. PMID:26098105

  17. Temporal expression of neuronal connexins during hippocampal ontogeny.

    PubMed

    Rozental, R; Srinivas, M; Gökhan, S; Urban, M; Dermietzel, R; Kessler, J A; Spray, D C; Mehler, M F

    2000-04-01

    classes of genes involved in these seminal events: ID (inhibitor of differentiation)-1 and GAS (growth arrest-specific gene)5. When MK31 cells were maintained in an uncommitted state, levels of ID-1 mRNA were high and GAS5 transcripts were essentially undetectable. Application of cytokines that promote neuronal lineage commitment and cell cycle exit resulted in down-regulation of ID-1 and upregulation of GAS5 transcripts, whereas additional cytokine paradigms that promoted terminal neuronal differentiation resulted in the delayed down-regulation of GAS5 mRNA. Stable MK31 transfectants were generated for ID-1 and GAS5. In basal conditions, cellular proliferation was enhanced in the ID-1 transfectants and inhibited in the GAS5 transfectants when compared with control MK31 cells. When cytokine-mediated neurogenesis was examined in these transfected cell lines, constitutive expression of ID-1 inhibited and constitutive expression of GAS5 enhanced initial and terminal stages of neuronal differentiation, with evidence that terminal neuronal maturation in both transfectant lines was associated with decreased cellular viability, possibly due to the presence of conflicting cell cycle-associated developmental signals. These experimental reagents will prove to be valuable experimental tools to help define the functional interrelationships between changing profiles of connexin protein expression and cell cycle regulation during neuronal ontogeny in the mammalian brain. The present review summarizes the current state of research involving the temporal expression of such connexin types in differentiating hippocampal neurons and speculates on the possible role of these intercellular channels in the development and plasticity of the nervous system. In addition, we describe the functional properties and expression pattern of the newly discovered neuronal-specific gap junctional protein, Cx36, in the developing mouse fetal hippocampus and in the rat retina and brain.

  18. Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI

    PubMed Central

    Tomassy, Giulio Srubek; De Leonibus, Elvira; Jabaudon, Denis; Lodato, Simona; Alfano, Christian; Mele, Andrea; Macklis, Jeffrey D.; Studer, Michèle

    2010-01-01

    Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise. PMID:20133588

  19. Inducible and neuronal nitric oxide synthases exert contrasting effects during rat intestinal recovery following fasting.

    PubMed

    Ito, Junta; Uchida, Hiroyuki; Machida, Naomi; Ohtake, Kazuo; Saito, Yuki; Kobayashi, Jun

    2017-04-01

    We investigated the effects of endogenous inducible (iNOS) and neuronal nitric oxide synthase on recovery from intestinal mucosal atrophy caused by fasting-induced apoptosis and decreased cell proliferation during refeeding in rats. Rats were divided into five groups, one of which was fed ad libitum, and four of which underwent 72 h of fasting, followed by refeeding for 0, 6, 24, and 48 h, respectively. iNOS and neuronal nitric oxide synthase mRNA and protein levels in jejunal tissues were measured, and mucosal height was histologically evaluated. Apoptotic indices, interferon-γ (IFN-γ) transcription levels, nitrite levels (as a measure of nitric oxide [NO] production),8-hydroxydeoxyguanosine formation (indicating reactive oxygen species [ROS] levels), crypt cell proliferation, and the motility indices (MI) were also estimated. Associations between mucosal height and NOS protein levels were determined using Spearman's rank correlation test. Notably, we observed significant increases in mucosal height and in neuronal nitric oxide synthase mRNA and protein expression as refeeding time increased. Indeed, there was a significant positive correlation between neuronal nitric oxide synthase protein level and mucosal height during the 48-h refeeding period ( r = 0.725, P < 0.01). Conversely, iNOS mRNA and protein expression decreased according to refeeding time, with a significant negative correlation between iNOS protein level and mucosal height being recorded during the 48-h refeeding period ( r = -0.898, P < 0.01). We also noted a significant negative correlation between jejunal neuronal nitric oxide synthase and iNOS protein concentrations over this same period ( r = -0.734, P < 0.01). Refeeding also restored the decreased jejunal MI caused by fasting. Our finding suggests that refeeding likely repairs fasting-induced jejunal atrophy by suppressing iNOS expression and subsequently inhibiting NO, ROS, and IFN-γ as apoptosis mediators, and by

  20. The endocannabinoid N-arachidonoyldopamine (NADA) exerts neuroprotective effects after excitotoxic neuronal damage via cannabinoid receptor 1 (CB(1)).

    PubMed

    Grabiec, Urszula; Koch, Marco; Kallendrusch, Sonja; Kraft, Robert; Hill, Kerstin; Merkwitz, Claudia; Ghadban, Chalid; Lutz, Beat; Straiker, Alex; Dehghani, Faramarz

    2012-03-01

    Endocannabinoids exert numerous effects in the CNS under physiological and pathological conditions. The aim of the present study was to examine whether the endocannabinoid N-arachidonoyldopamine (NADA) may protect neurons in excitotoxically lesioned organotypic hippocampal slice cultures (OHSC). OHSC were excitotoxically lesioned by application of N-methyl-d-aspartate (NMDA, 50 μM) for 4 h and subsequently treated with different NADA concentrations (0.1 pM-50 μM) alone or in combination with cannabinoid receptor antagonists. NADA protected dentate gyrus granule cells and caused a slight reduction in the number of microglial cells. The number of degenerated neurons significantly decreased between 100 pM and 10 μM NADA (p < 0.05). To identify the responsive receptor type of NADA mediated neuroprotection, we applied the cannabinoid (CB) receptor 1 (CB(1)) inverse agonist/antagonist AM251, CB(2) inverse agonist/antagonist AM630, abnormal-cannabidiol (abn-CBD)-sensitive receptor antagonist O-1918, transient receptor potential channel V1 (TRPV1) antagonist 6-iodonordihydrocapsaicin and A1 (TRPA1) antagonist HC-030031. Neuroprotective properties of low (1 nM) but not high (10 μM) NADA concentrations were solely blocked by AM251 and were absent in CB(1)(-/-) mice. AM630, O-1918, 6-iodonordihydrocapsaicin and HC-030031 showed no effects at all NADA concentrations applied. Our findings demonstrate that NADA protects dentate gyrus granule cells by acting via CB(1). NADA reduced the number of microglial cells at distinct concentrations. TRPV1 and TRPA1 were not involved in NADA mediated neuroprotection. Thus, our data implicate that NADA mediated activation of neuronal CB(1) may serve as a novel pharmacological target to mitigate symptoms of neuronal damage.

  1. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

    PubMed

    Jones, Nicholas A; Glyn, Sarah E; Akiyama, Satoshi; Hill, Thomas D M; Hill, Andrew J; Weston, Samantha E; Burnett, Matthew D A; Yamasaki, Yuki; Stephens, Gary J; Whalley, Benjamin J; Williams, Claire M

    2012-06-01

    Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazole-induced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (≥ 10 mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic-clonic seizures. These results extend the anti-convulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies.

  2. Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease

    PubMed Central

    Boukhzar, Loubna; Hamieh, Abdallah; Cartier, Dorthe; Tanguy, Yannick; Alsharif, Ifat; Castex, Matthieu; Arabo, Arnaud; Hajji, Sana El; Bonnet, Jean-Jacques; Errami, Mohammed; Falluel-Morel, Anthony; Chagraoui, Abdeslam; Lihrmann, Isabelle

    2016-01-01

    Abstract Aims: Oxidative stress is central to the pathogenesis of Parkinson's disease (PD), but the mechanisms involved in the control of this stress in dopaminergic cells are not fully understood. There is increasing evidence that selenoproteins play a central role in the control of redox homeostasis and cell defense, but the precise contribution of members of this family of proteins during the course of neurodegenerative diseases is still elusive. Results: We demonstrated first that selenoprotein T (SelT) whose gene disruption is lethal during embryogenesis, exerts a potent oxidoreductase activity. In the SH-SY5Y cell model of dopaminergic neurons, both silencing and overexpression of SelT affected oxidative stress and cell survival. Treatment with PD-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone triggered SelT expression in the nigrostriatal pathway of wild-type mice, but provoked rapid and severe parkinsonian-like motor defects in conditional brain SelT-deficient mice. This motor impairment was associated with marked oxidative stress and neurodegeneration and decreased tyrosine hydroxylase activity and dopamine levels in the nigrostriatal system. Finally, in PD patients, we report that SelT is tremendously increased in the caudate putamen tissue. Innovation: These results reveal the activity of a novel selenoprotein enzyme that protects dopaminergic neurons against oxidative stress and prevents early and severe movement impairment in animal models of PD. Conclusions: Our findings indicate that selenoproteins such as SelT play a crucial role in the protection of dopaminergic neurons against oxidative stress and cell death, providing insight into the molecular underpinnings of this stress in PD. Antioxid. Redox Signal. 24, 557–574. PMID:26866473

  3. Functional differentiation of macaque visual temporal cortical neurons using a parametric action space.

    PubMed

    Vangeneugden, Joris; Pollick, Frank; Vogels, Rufin

    2009-03-01

    Neurons in the rostral superior temporal sulcus (STS) are responsive to displays of body movements. We employed a parametric action space to determine how similarities among actions are represented by visual temporal neurons and how form and motion information contributes to their responses. The stimulus space consisted of a stick-plus-point-light figure performing arm actions and their blends. Multidimensional scaling showed that the responses of temporal neurons represented the ordinal similarity between these actions. Further tests distinguished neurons responding equally strongly to static presentations and to actions ("snapshot" neurons), from those responding much less strongly to static presentations, but responding well when motion was present ("motion" neurons). The "motion" neurons were predominantly found in the upper bank/fundus of the STS, and "snapshot" neurons in the lower bank of the STS and inferior temporal convexity. Most "motion" neurons showed strong response modulation during the course of an action, thus responding to action kinematics. "Motion" neurons displayed a greater average selectivity for these simple arm actions than did "snapshot" neurons. We suggest that the "motion" neurons code for visual kinematics, whereas the "snapshot" neurons code for form/posture, and that both can contribute to action recognition, in agreement with computation models of action recognition.

  4. Characterization of neurons in the cortical white matter in human temporal lobe epilepsy.

    PubMed

    Richter, Zsófia; Janszky, József; Sétáló, György; Horváth, Réka; Horváth, Zsolt; Dóczi, Tamás; Seress, László; Ábrahám, Hajnalka

    2016-10-01

    The aim of the present work was to characterize neurons in the archi- and neocortical white matter, and to investigate their distribution in mesial temporal sclerosis. Immunohistochemistry and quantification of neurons were performed on surgically resected tissue sections of patients with therapy-resistant temporal lobe epilepsy. Temporal lobe tissues of patients with tumor but without epilepsy and that from autopsy were used as controls. Neurons were identified with immunohistochemistry using antibodies against NeuN, calcium-binding proteins, transcription factor Tbr1 and neurofilaments. We found significantly higher density of neurons in the archi- and neocortical white matter of patients with temporal lobe epilepsy than in that of controls. Based on their morphology and neurochemical content, both excitatory and inhibitory cells were present among these neurons. A subset of neurons in the white matter was Tbr-1-immunoreactive and these neurons coexpressed NeuN and neurofilament marker SMI311R. No colocalization of Tbr1 was observed with the inhibitory neuronal markers, calcium-binding proteins. We suggest that a large population of white matter neurons comprises remnants of the subplate. Furthermore, we propose that a subset of white matter neurons was arrested during migration, highlighting the role of cortical maldevelopment in epilepsy associated with mesial temporal sclerosis. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. The potent inducible nitric oxide synthase inhibitor ONO-1714 inhibits neuronal NOS and exerts antinociception in rats.

    PubMed

    Sekiguchi, Fumiko; Mita, Yoko; Kamanaka, Yoshihisa; Kawao, Naoyuki; Matsuya, Hidekazu; Taga, Chiyomi; Kawabata, Atsufumi

    2004-07-22

    We evaluated if ONO-1714, known as an inducible nitric oxide synthase (iNOS) inhibitor, could inhibit neuronal NOS (nNOS) and exert antinociception. ONO-1714 potently inhibited both crude rat cerebellar NOS and recombinant human nNOS in vitro. Systemic ONO-1714 at 1-10 mg/kg suppressed carrageenan-induced thermal hyperalgesia in rats, an effect being equivalent to the antinociception caused by L-NAME or 7-nitroindazole at 25 mg/kg. The same doses of ONO-1714 also caused hypertension. Intrathecal (i.t.) ONO-1714 potently reduced the hyperalgesia, the effective dose range (0.2-0.6 microg/rat) being much lower than the antinociceptive dose (150 microg/rat) of i.t. L-NAME. Thus, ONO-1714 is considered a potent inhibitor of nNOS in addition to iNOS. The distinct relative antinociceptive activities of systemic and i.t. ONO-1714 are attributable to its possible poor blood-brain barrier permeability.

  6. Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding

    PubMed Central

    Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

    2016-01-01

    Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information. PMID:27304526

  7. Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding.

    PubMed

    Huang, Chao; Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

    2016-06-01

    Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information.

  8. Active engagement improves primary auditory cortical neurons' ability to discriminate temporal modulation.

    PubMed

    Niwa, Mamiko; Johnson, Jeffrey S; O'Connor, Kevin N; Sutter, Mitchell L

    2012-07-04

    The effect of attention on single neuron responses in the auditory system is unresolved. We found that when monkeys discriminated temporally amplitude modulated (AM) from unmodulated sounds, primary auditory cortical (A1) neurons better discriminated those sounds than when the monkeys were not discriminating them. This was observed for both average firing rate and vector strength (VS), a measure of how well neurons temporally follow the stimulus' temporal modulation. When data were separated by nonsynchronized and synchronized responses, the firing rate of nonsynchronized responses best distinguished AM- noise from unmodulated noise, followed by VS for synchronized responses, with firing rate for synchronized neurons providing the poorest AM discrimination. Firing rate-based AM discrimination for synchronized neurons, however, improved most with task engagement, showing that the least sensitive code in the passive condition improves the most with task engagement. Rate coding improved due to larger increases in absolute firing rate at higher modulation depths than for lower depths and unmodulated sounds. Relative to spontaneous activity (which increased with engagement), the response to unmodulated sounds decreased substantially. The temporal coding improvement--responses more precisely temporally following a stimulus when animals were required to attend to it--expands the framework of possible mechanisms of attention to include increasing temporal precision of stimulus following. These findings provide a crucial step to understanding the coding of temporal modulation and support a model in which rate and temporal coding work in parallel, permitting a multiplexed code for temporal modulation, and for a complementary representation of rate and temporal coding.

  9. Pre-learning stress that is temporally removed from acquisition exerts sex-specific effects on long-term memory.

    PubMed

    Zoladz, Phillip R; Warnecke, Ashlee J; Woelke, Sarah A; Burke, Hanna M; Frigo, Rachael M; Pisansky, Julia M; Lyle, Sarah M; Talbot, Jeffery N

    2013-02-01

    We have examined the influence of sex and the perceived emotional nature of learned information on pre-learning stress-induced alterations of long-term memory. Participants submerged their dominant hand in ice cold (stress) or warm (no stress) water for 3 min. Thirty minutes later, they studied 30 words, rated the words for their levels of emotional valence and arousal and were then given an immediate free recall test. Twenty-four hours later, participants' memory for the word list was assessed via delayed free recall and recognition assessments. The resulting memory data were analyzed after categorizing the studied words (i.e., distributing them to "positive-arousing", "positive-non-arousing", "negative-arousing", etc. categories) according to participants' valence and arousal ratings of the words. The results revealed that participants exhibiting a robust cortisol response to stress exhibited significantly impaired recognition memory for neutral words. More interestingly, however, males displaying a robust cortisol response to stress demonstrated significantly impaired recall, overall, and a marginally significant impairment of overall recognition memory, while females exhibiting a blunted cortisol response to stress demonstrated a marginally significant impairment of overall recognition memory. These findings support the notion that a brief stressor that is temporally separated from learning can exert deleterious effects on long-term memory. However, they also suggest that such effects depend on the sex of the organism, the emotional salience of the learned information and the degree to which stress increases corticosteroid levels.

  10. Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals.

    PubMed

    Baker, Christa A; Ma, Lisa; Casareale, Chelsea R; Carlson, Bruce A

    2016-08-24

    In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ∼8-12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. The timing patterns of action potentials, or spikes, play important roles in representing

  11. Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals

    PubMed Central

    Baker, Christa A.; Ma, Lisa; Casareale, Chelsea R.

    2016-01-01

    In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ∼8–12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. SIGNIFICANCE STATEMENT The timing patterns of action potentials, or spikes, play important

  12. Temporal properties of inferior colliculus neurons to photonic stimulation in the cochlea

    PubMed Central

    Tan, Xiaodong; Young, Hunter; Matic, Agnella Izzo; Zirkle, Whitney; Rajguru, Suhrud; Richter, Claus-Peter

    2015-01-01

    Infrared neural stimulation (INS) may be beneficial in auditory prostheses because of its spatially selective activation of spiral ganglion neurons. However, the response properties of single auditory neurons to INS and the possible contributions of its optoacoustic effects are yet to be examined. In this study, the temporal properties of auditory neurons in the central nucleus of the inferior colliculus (ICC) of guinea pigs in response to INS were characterized. Spatial selectivity of INS was observed along the tonotopically organized ICC. Trains of laser pulses and trains of acoustic clicks were used to evoke single unit responses in ICC of normal hearing animals. In response to INS, ICC neurons showed lower limiting rates, longer latencies, and lower firing efficiencies. In deaf animals, ICC neurons could still be stimulated by INS while unresponsive to acoustic stimulation. The site and spatial selectivity of INS both likely shaped the temporal properties of ICC neurons. PMID:26311831

  13. Temporal expectation and spectral expectation operate in distinct fashion on neuronal populations.

    PubMed

    Hsu, Yi-Fang; Hämäläinen, Jarmo A; Waszak, Florian

    2013-11-01

    The formation of temporal expectation (i.e., the prediction of "when") is of prime importance to sensory processing. It can modulate sensory processing at early processing stages probably via the entrainment of low-frequency neuronal oscillations in the brain. However, sensory predictions involve not only temporal expectation but also spectral expectation (i.e., the prediction of "what"). Here we investigated how temporal expectation may interrelate with spectral expectation by explicitly setting up temporal expectation and spectral expectation in a target detection task. We found that reaction time (RT) was shorter when targets were temporally expected than when they were temporally unexpected. The temporal expectation effect was larger with than without spectral expectation. However, this interaction in the behavioural data did not result from an interaction in the electroencephalography (EEG), where we observed independent main effects of temporal expectation and spectral expectation. More precisely, we found that the N1 and P2 event-related potential (ERP) components and the entrainment of low-frequency neuronal oscillations were exclusively modulated by temporal expectation, whilst only the P3 ERP component was modulated by spectral expectation. Our results, thus, support the idea that temporal expectation and spectral expectation operate in distinct fashion on neuronal populations.

  14. Segment-Specific Neuronal Subtype Specification by the Integration of Anteroposterior and Temporal Cues

    PubMed Central

    Karlsson, Daniel; Baumgardt, Magnus; Thor, Stefan

    2010-01-01

    The generation of distinct neuronal subtypes at different axial levels relies upon both anteroposterior and temporal cues. However, the integration between these cues is poorly understood. In the Drosophila central nervous system, the segmentally repeated neuroblast 5–6 generates a unique group of neurons, the Apterous (Ap) cluster, only in thoracic segments. Recent studies have identified elaborate genetic pathways acting to control the generation of these neurons. These insights, combined with novel markers, provide a unique opportunity for addressing how anteroposterior and temporal cues are integrated to generate segment-specific neuronal subtypes. We find that Pbx/Meis, Hox, and temporal genes act in three different ways. Posteriorly, Pbx/Meis and posterior Hox genes block lineage progression within an early temporal window, by triggering cell cycle exit. Because Ap neurons are generated late in the thoracic 5–6 lineage, this prevents generation of Ap cluster cells in the abdomen. Thoracically, Pbx/Meis and anterior Hox genes integrate with late temporal genes to specify Ap clusters, via activation of a specific feed-forward loop. In brain segments, “Ap cluster cells” are present but lack both proper Hox and temporal coding. Only by simultaneously altering Hox and temporal gene activity in all segments can Ap clusters be generated throughout the neuroaxis. This study provides the first detailed analysis, to our knowledge, of an identified neuroblast lineage along the entire neuroaxis, and confirms the concept that lineal homologs of truncal neuroblasts exist throughout the developing brain. We furthermore provide the first insight into how Hox/Pbx/Meis anteroposterior and temporal cues are integrated within a defined lineage, to specify unique neuronal identities only in thoracic segments. This study reveals a surprisingly restricted, yet multifaceted, function of both anteroposterior and temporal cues with respect to lineage control and cell fate

  15. Macaque inferior temporal neurons are selective for three-dimensional boundaries and surfaces.

    PubMed

    Janssen, P; Vogels, R; Liu, Y; Orban, G A

    2001-12-01

    The lower bank of the superior temporal sulcus (TEs), part of the inferior temporal cortex, contains neurons selective for disparity-defined three-dimensional (3-D) shape. The large majority of these TEs neurons respond to the spatial variation of disparity, i.e., are higher-order disparity selective. To determine whether curved boundaries or curved surfaces by themselves are sufficient to elicit 3-D shape selectivity, we recorded the responses of single higher-order disparity-selective TEs neurons to concave and convex 3-D shapes in which the disparity varied either along the boundary of the shape, or only along its surface. For a majority of neurons, a 3-D boundary was sufficient for 3-D shape selectivity. At least as many neurons responded selectively to 3-D surfaces, and a number of neurons exhibited both surface and boundary selectivity. The second aim of this study was to determine whether TEs neurons can represent differences in second-order disparities along the horizontal axis. The results revealed that TEs neurons can also be selective for horizontal 3-D shapes and can code the direction of curvature (vertical or horizontal). Thus, TEs neurons represent both boundaries and surfaces curved in depth and can signal the direction of curvature along a surface. These results show that TEs neurons use not only boundary but also surface information to encode 3-D shape properties.

  16. Passive and active membrane properties contribute to the temporal filtering properties of midbrain neurons in vivo.

    PubMed

    Fortune, E S; Rose, G J

    1997-05-15

    This study examined the contributions of passive and active membrane properties to the temporal selectivities of electrosensory neurons in vivo. The intracellular responses to time-varying (2-30 Hz) electrosensory stimulation and current injection of 27 neurons in the midbrain of the weakly electric fish Eigenmannia were recorded. Each neuron was filled with biocytin to reveal its anatomy. Neurons were divided into two biophysically distinct groups based on their frequency-dependent responses to sinusoidal current injection over the range 2-30 Hz. Fourteen neurons showed low-pass filtering, with a maximum decline in the amplitude of voltage responses of >2.6 dB (X = 4.30 dB, s = 1.10 dB) to sinusoidal current injection. These neurons also showed low-pass filtering of electrosensory information but with larger maximum declines in postsynaptic potential amplitude (X = 9.53 dB, s = 3.34 dB; n = 10). These neurons had broad dendritic arbors and relatively spiny dendrites. Five neurons showed all-pass filtering, having maximum decline in the amplitude of voltage responses of <2.0 dB (X = 1.16 dB, s = 0.61 dB). For electrosensory stimuli, however, these neurons showed low-, band-, or high-pass filtering. These neurons had small dendritic arbors and few or no spines. Voltage-dependent "active" conductances were revealed in eight neurons by using several levels of current clamp. In four of these neurons, the duration of the voltage-dependent conductances decreased in concert with the period of the electrosensory stimulus, whereas in the other four neurons the duration of the voltage-dependent conductances was relatively short (<30 msec) and nearly constant across sensory stimulation frequencies. These conductances enhanced the temporal filtering properties of neurons.

  17. Short-Term Depression, Temporal Summation, and Onset Inhibition Shape Interval Tuning in Midbrain Neurons

    PubMed Central

    Baker, Christa A.

    2014-01-01

    A variety of synaptic mechanisms can contribute to single-neuron selectivity for temporal intervals in sensory stimuli. However, it remains unknown how these mechanisms interact to establish single-neuron sensitivity to temporal patterns of sensory stimulation in vivo. Here we address this question in a circuit that allows us to control the precise temporal patterns of synaptic input to interval-tuned neurons in behaviorally relevant ways. We obtained in vivo intracellular recordings under multiple levels of current clamp from midbrain neurons in the mormyrid weakly electric fish Brienomyrus brachyistius during stimulation with electrosensory pulse trains. To reveal the excitatory and inhibitory inputs onto interval-tuned neurons, we then estimated the synaptic conductances underlying responses. We found short-term depression in excitatory and inhibitory pathways onto all interval-tuned neurons. Short-interval selectivity was associated with excitation that depressed less than inhibition at short intervals, as well as temporally summating excitation. Long-interval selectivity was associated with long-lasting onset inhibition. We investigated tuning after separately nullifying the contributions of temporal summation and depression, and found the greatest diversity of interval selectivity among neurons when both mechanisms were at play. Furthermore, eliminating the effects of depression decreased sensitivity to directional changes in interval. These findings demonstrate that variation in depression and summation of excitation and inhibition helps to establish tuning to behaviorally relevant intervals in communication signals, and that depression contributes to neural coding of interval sequences. This work reveals for the first time how the interplay between short-term plasticity and temporal summation mediates the decoding of temporal sequences in awake, behaving animals. PMID:25339741

  18. Temporal Cohorts of Lineage-Related Neurons Perform Analogous Functions in Distinct Sensorimotor Circuits.

    PubMed

    Wreden, Christopher C; Meng, Julia L; Feng, Weidong; Chi, Wanhao; Marshall, Zarion D; Heckscher, Ellie S

    2017-05-22

    Neuronal stem cell lineages are the fundamental developmental units of the brain, and neuronal circuits are the fundamental functional units of the brain. Determining lineage-circuitry relationships is essential for deciphering the developmental logic of circuit assembly. While the spatial distribution of lineage-related neurons has been investigated in a few brain regions [1-9], an important, but unaddressed question is whether temporal information that diversifies neuronal progeny within a single lineage also impacts circuit assembly. Circuits in the sensorimotor system (e.g., spinal cord) are thought to be assembled sequentially [10-14], making this an ideal brain region for investigating the circuit-level impact of temporal patterning within a lineage. Here, we use intersectional genetics, optogenetics, high-throughput behavioral analysis, single-neuron labeling, connectomics, and calcium imaging to determine how a set of bona fide lineage-related interneurons contribute to sensorimotor circuitry in the Drosophila larva. We show that Even-skipped lateral interneurons (ELs) are sensory processing interneurons. Late-born ELs contribute to a proprioceptive body posture circuit, whereas early-born ELs contribute to a mechanosensitive escape circuit. These data support a model in which a single neuronal stem cell can produce a large number of interneurons with similar functional capacity that are distributed into different circuits based on birth timing. In summary, these data establish a link between temporal specification of neuronal identity and circuit assembly at the single-cell level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The Chronotron: A Neuron That Learns to Fire Temporally Precise Spike Patterns

    PubMed Central

    Florian, Răzvan V.

    2012-01-01

    In many cases, neurons process information carried by the precise timings of spikes. Here we show how neurons can learn to generate specific temporally precise output spikes in response to input patterns of spikes having precise timings, thus processing and memorizing information that is entirely temporally coded, both as input and as output. We introduce two new supervised learning rules for spiking neurons with temporal coding of information (chronotrons), one that provides high memory capacity (E-learning), and one that has a higher biological plausibility (I-learning). With I-learning, the neuron learns to fire the target spike trains through synaptic changes that are proportional to the synaptic currents at the timings of real and target output spikes. We study these learning rules in computer simulations where we train integrate-and-fire neurons. Both learning rules allow neurons to fire at the desired timings, with sub-millisecond precision. We show how chronotrons can learn to classify their inputs, by firing identical, temporally precise spike trains for different inputs belonging to the same class. When the input is noisy, the classification also leads to noise reduction. We compute lower bounds for the memory capacity of chronotrons and explore the influence of various parameters on chronotrons' performance. The chronotrons can model neurons that encode information in the time of the first spike relative to the onset of salient stimuli or neurons in oscillatory networks that encode information in the phases of spikes relative to the background oscillation. Our results show that firing one spike per cycle optimizes memory capacity in neurons encoding information in the phase of firing relative to a background rhythm. PMID:22879876

  20. Frontal Neurons Modulate Memory Retrieval across Widely Varying Temporal Scales

    ERIC Educational Resources Information Center

    Zhang, Wen-Hua; Williams, Ziv M.

    2015-01-01

    Once a memory has formed, it is thought to undergo a gradual transition within the brain from short- to long-term storage. This putative process, however, also poses a unique problem to the memory system in that the same learned items must also be retrieved across broadly varying time scales. Here, we find that neurons in the ventrolateral…

  1. Dysmorphic neurons in patients with temporal lobe epilepsy.

    PubMed

    da Silva, Alexandre Valotta; Houzel, Jean Christophe; Targas Yacubian, Elza Marcia; Carrete, Henrique; Sakamoto, Américo Ceiki; Priel, Margareth Rose; Martins, Heloise Helena; Oliveira, Ivanilson; Garzon, Eliana; Stavale, João Norberto; da Silva Centeno, Ricardo; Machado, Helio; Cavalheiro, Esper Abrão

    2006-02-09

    We studied morphologic characteristics of dysmorphic neurons in the hippocampus of seven patients with medically intractable TLE and compare histological, clinical, and imaging features with ten TLE patients with classical hippocampal sclerosis without abnormal cells. Such dysmorphic neurons were observed in the hilus of the dentate gyrus and were characterized by giant or misshapen cells with abnormal cytoskeletal structure and atypical dendritic processes that resembled the dysmorphic neurons from cortical dysplasias. Specimens with dysmorphic cells also contained other cytoarchitectural abnormalities including bilamination of the dentate granular cell layer (four out seven cases), and the presence of Cajal-Retzius cells in the dentate gyrus or Ammon's horn (five out seven cases). There were no statistically significant differences regarding the age at onset, duration of epilepsy, and hippocampal asymmetry ratio between patients with or without dysmorphic cells. Nevertheless, it is interesting to note that a higher proportion of patients with dysmorphic neurons continued to present auras after surgery, when compared with patients without those cells.

  2. Frontal Neurons Modulate Memory Retrieval across Widely Varying Temporal Scales

    ERIC Educational Resources Information Center

    Zhang, Wen-Hua; Williams, Ziv M.

    2015-01-01

    Once a memory has formed, it is thought to undergo a gradual transition within the brain from short- to long-term storage. This putative process, however, also poses a unique problem to the memory system in that the same learned items must also be retrieved across broadly varying time scales. Here, we find that neurons in the ventrolateral…

  3. Neuronal long-range temporal correlations and avalanche dynamics are correlated with behavioral scaling laws.

    PubMed

    Palva, J Matias; Zhigalov, Alexander; Hirvonen, Jonni; Korhonen, Onerva; Linkenkaer-Hansen, Klaus; Palva, Satu

    2013-02-26

    Scale-free fluctuations are ubiquitous in behavioral performance and neuronal activity. In time scales from seconds to hundreds of seconds, psychophysical dynamics and the amplitude fluctuations of neuronal oscillations are governed by power-law-form long-range temporal correlations (LRTCs). In millisecond time scales, neuronal activity comprises cascade-like neuronal avalanches that exhibit power-law size and lifetime distributions. However, it remains unknown whether these neuronal scaling laws are correlated with those characterizing behavioral performance or whether neuronal LRTCs and avalanches are related. Here, we show that the neuronal scaling laws are strongly correlated both with each other and with behavioral scaling laws. We used source reconstructed magneto- and electroencephalographic recordings to characterize the dynamics of ongoing cortical activity. We found robust power-law scaling in neuronal LRTCs and avalanches in resting-state data and during the performance of audiovisual threshold stimulus detection tasks. The LRTC scaling exponents of the behavioral performance fluctuations were correlated with those of concurrent neuronal avalanches and LRTCs in anatomically identified brain systems. The behavioral exponents also were correlated with neuronal scaling laws derived from a resting-state condition and with a similar anatomical topography. Finally, despite the difference in time scales, the scaling exponents of neuronal LRTCs and avalanches were strongly correlated during both rest and task performance. Thus, long and short time-scale neuronal dynamics are related and functionally significant at the behavioral level. These data suggest that the temporal structures of human cognitive fluctuations and behavioral variability stem from the scaling laws of individual and intrinsic brain dynamics.

  4. Role of synaptic dynamics and heterogeneity in neuronal learning of temporal code

    PubMed Central

    Rotman, Ziv

    2013-01-01

    Temporal codes are believed to play important roles in neuronal representation of information. Neuronal ability to classify and learn temporal spiking patterns is thus essential for successful extraction and processing of information. Understanding neuronal learning of temporal code has been complicated, however, by the intrinsic stochasticity of synaptic transmission. Using a computational model of a learning neuron, the tempotron, we studied the effects of synaptic unreliability and short-term dynamics on the neuron's ability to learn spike timing rules. Our results suggest that such a model neuron can learn to classify spike timing patterns even with unreliable synapses, albeit with a significantly reduced success rate. We explored strategies to improve correct spike timing classification and found that firing clustered spike bursts significantly improves learning performance. Furthermore, rapid activity-dependent modulation of synaptic unreliability, implemented with realistic models of dynamic synapses, further improved classification of different burst properties and spike timing modalities. Neuronal models with only facilitating or only depressing inputs exhibited preference for specific types of spike timing rules, but a mixture of facilitating and depressing synapses permitted much improved learning of multiple rules. We tested applicability of these findings to real neurons by considering neuronal learning models with the naturally distributed input release probabilities found in excitatory hippocampal synapses. Our results suggest that spike bursts comprise several encoding modalities that can be learned effectively with stochastic dynamic synapses, and that distributed release probabilities significantly improve learning performance. Synaptic unreliability and dynamics may thus play important roles in the neuron's ability to learn spike timing rules during decoding. PMID:23926043

  5. Role of synaptic dynamics and heterogeneity in neuronal learning of temporal code.

    PubMed

    Rotman, Ziv; Klyachko, Vitaly A

    2013-11-01

    Temporal codes are believed to play important roles in neuronal representation of information. Neuronal ability to classify and learn temporal spiking patterns is thus essential for successful extraction and processing of information. Understanding neuronal learning of temporal code has been complicated, however, by the intrinsic stochasticity of synaptic transmission. Using a computational model of a learning neuron, the tempotron, we studied the effects of synaptic unreliability and short-term dynamics on the neuron's ability to learn spike timing rules. Our results suggest that such a model neuron can learn to classify spike timing patterns even with unreliable synapses, albeit with a significantly reduced success rate. We explored strategies to improve correct spike timing classification and found that firing clustered spike bursts significantly improves learning performance. Furthermore, rapid activity-dependent modulation of synaptic unreliability, implemented with realistic models of dynamic synapses, further improved classification of different burst properties and spike timing modalities. Neuronal models with only facilitating or only depressing inputs exhibited preference for specific types of spike timing rules, but a mixture of facilitating and depressing synapses permitted much improved learning of multiple rules. We tested applicability of these findings to real neurons by considering neuronal learning models with the naturally distributed input release probabilities found in excitatory hippocampal synapses. Our results suggest that spike bursts comprise several encoding modalities that can be learned effectively with stochastic dynamic synapses, and that distributed release probabilities significantly improve learning performance. Synaptic unreliability and dynamics may thus play important roles in the neuron's ability to learn spike timing rules during decoding.

  6. Temporal synchrony and gamma to theta power conversion in the dendrites of CA1 pyramidal neurons

    PubMed Central

    Vaidya, Sachin P.; Johnston, Daniel

    2014-01-01

    Timing is a crucial aspect of synaptic integration. For pyramidal neurons that integrate thousands of synaptic inputs spread across hundreds of microns, it is thus a challenge to maintain the timing of incoming inputs at the axo-somatic integration site. Here we show that pyramidal neurons in the rodent hippocampus use a gradient of inductance in the form of HCN channels as an active mechanism to counteract location-dependent temporal differences of dendritic inputs at the soma. Using simultaneous multi-site whole cell recordings complemented by computational modeling, we find that this intrinsic biophysical mechanism produces temporal synchrony of rhythmic inputs in the theta and gamma frequency ranges across wide regions of the dendritic tree. While gamma and theta oscillations are known to synchronize activity across space in neuronal networks, our results identify a novel mechanism by which this synchrony extends to activity within single pyramidal neurons with complex dendritic arbors. PMID:24185428

  7. Spatio-temporal feature maps using gated neuronal architecture.

    PubMed

    Chandrasekaran, V; Palaniswami, M; Caelli, T M

    1995-01-01

    In this paper, Kohonen's self-organizing feature map is modified by a novel technique of allowing the neurons in the feature map to compete in a selective manner. The selective competition is achieved by grating the N-dimensional feature space using a spatial frequency and setting a criterion for the neurons to compete based on the region in which the input pattern resides. The spatial grating and selective competition are achieved by introducing a gated neuronal architecture in the feature map. As the selection criterion changes with time, it generates a time sequence of winning node indexes providing more input information and potentially allowing higher classification performance. These time sequences are then used to predict the class label of the input pattern more accurately. Three possible class label prediction algorithms are formulated based on evidential reasoning method and Bayes conditional probability theorem. These are tested on real world 8-class texture and a synthetic 12-class 3D object recognition problems. The classification performance is then compared with the results obtained by using a standard statistical linear discriminant analysis.

  8. Entorhinal-Hippocampal Neuronal Circuits Bridge Temporally Discontiguous Events

    ERIC Educational Resources Information Center

    Kitamura, Takashi; Macdonald, Christopher J.; Tonegawa, Susumu

    2015-01-01

    The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits…

  9. Entorhinal-Hippocampal Neuronal Circuits Bridge Temporally Discontiguous Events

    ERIC Educational Resources Information Center

    Kitamura, Takashi; Macdonald, Christopher J.; Tonegawa, Susumu

    2015-01-01

    The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits…

  10. Playing Well with Others: Extrinsic Cues Regulate Neural Progenitor Temporal Identity to Generate Neuronal Diversity.

    PubMed

    Syed, Mubarak Hussain; Mark, Brandon; Doe, Chris Q

    2017-09-09

    During neurogenesis, vertebrate and Drosophila progenitors change over time as they generate a diverse population of neurons and glia. Vertebrate neural progenitors have long been known to use both progenitor-intrinsic and progenitor-extrinsic cues to regulate temporal patterning. In contrast, virtually all temporal patterning mechanisms discovered in Drosophila neural progenitors (neuroblasts) involve progenitor-intrinsic temporal transcription factor cascades. Recent results, however, have revealed several extrinsic pathways that regulate Drosophila neuroblast temporal patterning: nutritional cues regulate the timing of neuroblast proliferation/quiescence and a steroid hormone cue that is required for temporal transcription factor expression. Here, we discuss newly discovered extrinsic cues regulating neural progenitor temporal identity in Drosophila, highlight conserved mechanisms, and raise open questions for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Impact of Partial Time Delay on Temporal Dynamics of Watts-Strogatz Small-World Neuronal Networks

    NASA Astrophysics Data System (ADS)

    Yan, Hao; Sun, Xiaojuan

    2017-06-01

    In this paper, we mainly discuss effects of partial time delay on temporal dynamics of Watts-Strogatz (WS) small-world neuronal networks by controlling two parameters. One is the time delay τ and the other is the probability of partial time delay pdelay. Temporal dynamics of WS small-world neuronal networks are discussed with the aid of temporal coherence and mean firing rate. With the obtained simulation results, it is revealed that for small time delay τ, the probability pdelay could weaken temporal coherence and increase mean firing rate of neuronal networks, which indicates that it could improve neuronal firings of the neuronal networks while destroying firing regularity. For large time delay τ, temporal coherence and mean firing rate do not have great changes with respect to pdelay. Time delay τ always has great influence on both temporal coherence and mean firing rate no matter what is the value of pdelay. Moreover, with the analysis of spike trains and histograms of interspike intervals of neurons inside neuronal networks, it is found that the effects of partial time delays on temporal coherence and mean firing rate could be the result of locking between the period of neuronal firing activities and the value of time delay τ. In brief, partial time delay could have great influence on temporal dynamics of the neuronal networks.

  12. Learning of anticipatory responses in single neurons of the human medial temporal lobe

    PubMed Central

    Reddy, Leila; Poncet, Marlene; Self, Matthew W.; Peters, Judith C.; Douw, Linda; van Dellen, Edwin; Claus, Steven; Reijneveld, Jaap C.; Baayen, Johannes C.; Roelfsema, Pieter R.

    2015-01-01

    Neuronal processes underlying the formation of new associations in the human brain are not yet well understood. Here human participants, implanted with depth electrodes in the brain, learned arbitrary associations between images presented in an ordered, predictable sequence. During learning we recorded from medial temporal lobe (MTL) neurons that responded to at least one of the pictures in the sequence (the preferred stimulus). We report that as a result of learning, single MTL neurons show asymmetric shifts in activity and start firing earlier in the sequence in anticipation of their preferred stimulus. These effects appear relatively early in learning, after only 11 exposures to the stimulus sequence. The anticipatory neuronal responses emerge while the subjects became faster in reporting the next item in the sequence. These results demonstrate flexible representations that could support learning of new associations between stimuli in a sequence, in single neurons in the human MTL. PMID:26449885

  13. Temporal selectivity in midbrain electrosensory neurons identified by modal variation in active sensing.

    PubMed

    Pluta, Scott R; Kawasaki, Masashi

    2010-07-01

    Mormyrid weakly electric fish actively sense their surroundings by continuously emitting discrete pulses of electricity separated by varying intervals of silence. The temporal pattern of this pulsing behavior is related to context. While resting in the absence of an overt stimulus, baseline interpulse intervals (IPIs) mostly range 200-450 ms, and sequential variation is relatively high. Spontaneously, or following the presentation of a novel stimulus, IPIs transiently shorten during the performance of an electromotor "burst" display. We made intracellular whole cell recordings in vivo from neurons in the lateral nucleus of the torus semicircularis while the fish's dynamic pulsing behavior modified the temporal pattern of stimulation. Stimulation was designed to simulate the spatial patterns of AM that occur during the electrolocation of a resistive object. We discovered that toral neurons selectively respond to stimulation during a particular mode of electromotor activity. Two types of temporally selective neurons were discovered: baseline-selective neurons that displayed significantly higher postsynaptic potential (PSP) amplitude and spike count per electric organ discharge (EOD) during baseline electromotor activity and burst-selective neurons that displayed significantly higher PSP amplitude and spike count per EOD during electromotor burst displays. Interval-dependent changes in the strength of excitation and inhibition contributed to their selectivity.

  14. The superior paraolivary nucleus shapes temporal response properties of neurons in the inferior colliculus

    PubMed Central

    Felix, Richard A.; Magnusson, Anna K.; Berrebi, Albert S.

    2014-01-01

    The mammalian superior paraolivary nucleus (SPON) is a major source of GABAergic inhibition to neurons in the inferior colliculus (IC), a well-studied midbrain nucleus that is the site of convergence and integration for the majority ascending auditory pathways en route to the cortex. Neurons in the SPON and IC exhibit highly precise responses to temporal sound features, which are important perceptual cues for naturally occurring sounds. To determine how inhibitory input from the SPON contributes to the encoding of temporal information in the IC, a reversible inactivation procedure was conducted to silence SPON neurons while recording responses to amplitude-modulated tones and silent gaps between tones in the IC. The results show that SPON-derived inhibition shapes responses of onset and sustained units in the IC via different mechanisms. Onset neurons appear to be driven primarily by excitatory inputs and their responses are shaped indirectly by SPON-derived inhibition, whereas sustained neurons are heavily influenced directly by transient offset inhibition from the SPON. The findings also demonstrate that a more complete dissection of temporal processing pathways is critical for understanding how biologically important sounds are encoded by the brain. PMID:24973970

  15. Flicker adaptation of low-level cortical visual neurons contributes to temporal dilation

    PubMed Central

    Ortega, Laura; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2013-01-01

    Several seconds of adaptation to a flickered stimulus causes a subsequent brief static stimulus to appear longer in duration. Non-sensory factors such as increased arousal and attention have been thought to mediate this flicker-based temporal-dilation aftereffect. Here we provide evidence that adaptation of low-level cortical visual neurons contributes to this aftereffect. The aftereffect was significantly reduced by a 45° change in Gabor orientation between adaptation and test. Because orientation-tuning bandwidths are smaller in lower-level cortical visual areas and are approximately 45° in human V1, the result suggests that flicker adaptation of orientation-tuned V1 neurons contributes to the temporal-dilation aftereffect. The aftereffect was abolished when the adaptor and test stimuli were presented to different eyes. Because eye preferences are strong in V1 but diminish in higher-level visual areas, the eye specificity of the aftereffect corroborates the involvement of low-level cortical visual neurons. Our results thus suggest that flicker adaptation of low-level cortical visual neurons contributes to expanding visual duration. Furthermore, this temporal-dilation aftereffect dissociates from the previously reported temporal-constriction aftereffect on the basis of the differences in their orientation and flicker-frequency selectivity, suggesting that the visual system possesses at least two distinct and potentially complementary mechanisms for adaptively coding perceived duration. PMID:22866761

  16. Development and modulation of intrinsic membrane properties control the temporal precision of auditory brain stem neurons.

    PubMed

    Franzen, Delwen L; Gleiss, Sarah A; Berger, Christina; Kümpfbeck, Franziska S; Ammer, Julian J; Felmy, Felix

    2015-01-15

    Passive and active membrane properties determine the voltage responses of neurons. Within the auditory brain stem, refinements in these intrinsic properties during late postnatal development usually generate short integration times and precise action-potential generation. This developmentally acquired temporal precision is crucial for auditory signal processing. How the interactions of these intrinsic properties develop in concert to enable auditory neurons to transfer information with high temporal precision has not yet been elucidated in detail. Here, we show how the developmental interaction of intrinsic membrane parameters generates high firing precision. We performed in vitro recordings from neurons of postnatal days 9-28 in the ventral nucleus of the lateral lemniscus of Mongolian gerbils, an auditory brain stem structure that converts excitatory to inhibitory information with high temporal precision. During this developmental period, the input resistance and capacitance decrease, and action potentials acquire faster kinetics and enhanced precision. Depending on the stimulation time course, the input resistance and capacitance contribute differentially to action-potential thresholds. The decrease in input resistance, however, is sufficient to explain the enhanced action-potential precision. Alterations in passive membrane properties also interact with a developmental change in potassium currents to generate the emergence of the mature firing pattern, characteristic of coincidence-detector neurons. Cholinergic receptor-mediated depolarizations further modulate this intrinsic excitability profile by eliciting changes in the threshold and firing pattern, irrespective of the developmental stage. Thus our findings reveal how intrinsic membrane properties interact developmentally to promote temporally precise information processing.

  17. The Roles of Human Lateral Temporal Cortical Neuronal Activity in Recent Verbal Memory Encoding

    PubMed Central

    Schoenfield-McNeill, Julie; Corina, David

    2009-01-01

    Activity of 98 single neurons in human lateral temporal cortex was measured during memory encoding for auditory words, text, or pictures and compared with identification of material of the same modality in extracellular recordings during awake neurosurgery for epilepsy. Frequency of activity was divided into early or late epochs or activity sustained throughout both; 44 neurons had significant changes in one or more categories. Polymodal and sustained changes lateralized to dominant hemisphere and late changes to nondominant. The majority of polymodal neurons shifted categories for different modalities. In dominant hemisphere, the timing and nature of changes in activity provide the basis for a model of the roles of temporal cortex in encoding. Superior temporal gyrus excitatory activity was related to the early epoch, when perception and processing occur, and middle gyrus to the late epoch, when semantic labeling occurs. The superior two-thirds of middle gyrus also demonstrated sustained inhibition. In a subset of lateral temporal neurons, memory-encoding activity reflected simultaneous convergence of sustained attentional and early perceptual inputs. PMID:18469317

  18. Temporal properties of inferior colliculus neurons to photonic stimulation in the cochlea.

    PubMed

    Tan, Xiaodong; Young, Hunter; Matic, Agnella Izzo; Zirkle, Whitney; Rajguru, Suhrud; Richter, Claus-Peter

    2015-08-01

    Infrared neural stimulation (INS) may be beneficial in auditory prostheses because of its spatially selective activation of spiral ganglion neurons. However, the response properties of single auditory neurons to INS and the possible contributions of its optoacoustic effects are yet to be examined. In this study, the temporal properties of auditory neurons in the central nucleus of the inferior colliculus (ICC) of guinea pigs in response to INS were characterized. Spatial selectivity of INS was observed along the tonotopically organized ICC. Trains of laser pulses and trains of acoustic clicks were used to evoke single unit responses in ICC of normal hearing animals. In response to INS, ICC neurons showed lower limiting rates, longer latencies, and lower firing efficiencies. In deaf animals, ICC neurons could still be stimulated by INS while unresponsive to acoustic stimulation. The site and spatial selectivity of INS both likely shaped the temporal properties of ICC neurons. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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

    PubMed

    Kamiński, Jan; Sullivan, Shannon; Chung, Jeffrey M; Ross, Ian B; Mamelak, Adam N; Rutishauser, Ueli

    2017-04-01

    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 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.

  20. 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

  1. The Hunchback temporal transcription factor establishes, but is not required to maintain, early-born neuronal identity.

    PubMed

    Hirono, Keiko; Kohwi, Minoree; Clark, Matt Q; Heckscher, Ellie S; Doe, Chris Q

    2017-01-31

    Drosophila and mammalian neural progenitors typically generate a diverse family of neurons in a stereotyped order. Neuronal diversity can be generated by the sequential expression of temporal transcription factors. In Drosophila, neural progenitors (neuroblasts) sequentially express the temporal transcription factors Hunchback (Hb), Kruppel, Pdm, and Castor. Hb is necessary and sufficient to specify early-born neuronal identity in multiple lineages, and is maintained in the post-mitotic neurons produced during each neuroblast expression window. Surprisingly, nothing is currently known about whether Hb acts in neuroblasts or post-mitotic neurons (or both) to specify first-born neuronal identity. Here we selectively remove Hb from post-mitotic neurons, and assay the well-characterized NB7-1 and NB1-1 lineages for defects in neuronal identity and function. We find that loss of Hb from embryonic and larval post-mitotic neurons does not affect neuronal identity. Furthermore, removing Hb from post-mitotic neurons throughout the entire CNS has no effect on larval locomotor velocity, a sensitive assay for motor neuron and pre-motor neuron function. We conclude that Hb functions in progenitors (neuroblasts/GMCs) to establish heritable neuronal identity that is maintained by a Hb-independent mechanism. We suggest that Hb acts in neuroblasts to establish an epigenetic state that is permanently maintained in early-born neurons.

  2. Spatio-temporal regulations and functions of neuronal alternative RNA splicing in developing and adult brains.

    PubMed

    Iijima, Takatoshi; Hidaka, Chiharu; Iijima, Yoko

    2016-08-01

    Alternative pre-mRNA splicing is a fundamental mechanism that generates molecular diversity from a single gene. In the central nervous system (CNS), key neural developmental steps are thought to be controlled by alternative splicing decisions, including the molecular diversity underlying synaptic wiring, plasticity, and remodeling. Significant progress has been made in understanding the molecular mechanisms and functions of alternative pre-mRNA splicing in neurons through studies in invertebrate systems; however, recent studies have begun to uncover the potential role of neuronal alternative splicing in the mammalian CNS. This article provides an overview of recent findings regarding the regulation and function of neuronal alternative splicing. In particular, we focus on the spatio-temporal regulation of neurexin, a synaptic adhesion molecule, by neuronal cell type-specific factors and neuronal activity, which are thought to be especially important for characterizing neural development and function within the mammalian CNS. Notably, there is increasing evidence that implicates the dysregulation of neuronal splicing events in several neurological disorders. Therefore, understanding the detailed mechanisms of neuronal alternative splicing in the mammalian CNS may provide plausible treatment strategies for these diseases.

  3. The impact of orientation filtering on face-selective neurons in monkey inferior temporal cortex.

    PubMed

    Taubert, Jessica; Goffaux, Valerie; Van Belle, Goedele; Vanduffel, Wim; Vogels, Rufin

    2016-02-16

    Faces convey complex social signals to primates. These signals are tolerant of some image transformations (e.g. changes in size) but not others (e.g. picture-plane rotation). By filtering face stimuli for orientation content, studies of human behavior and brain responses have shown that face processing is tuned to selective orientation ranges. In the present study, for the first time, we recorded the responses of face-selective neurons in monkey inferior temporal (IT) cortex to intact and scrambled faces that were filtered to selectively preserve horizontal or vertical information. Guided by functional maps, we recorded neurons in the lateral middle patch (ML), the lateral anterior patch (AL), and an additional region located outside of the functionally defined face-patches (CONTROL). We found that neurons in ML preferred horizontal-passed faces over their vertical-passed counterparts. Neurons in AL, however, had a preference for vertical-passed faces, while neurons in CONTROL had no systematic preference. Importantly, orientation filtering did not modulate the firing rate of neurons to phase-scrambled face stimuli in any recording region. Together these results suggest that face-selective neurons found in the face-selective patches are differentially tuned to orientation content, with horizontal tuning in area ML and vertical tuning in area AL.

  4. 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.

  5. Tyrosol exerts a protective effect against dopaminergic neuronal cell death in in vitro model of Parkinson's disease.

    PubMed

    Dewapriya, Pradeep; Himaya, S W A; Li, Yong-Xin; Kim, Se-Kwon

    2013-11-15

    Experimental evidence suggests that tyrosol [2-(4-hydroxyphenyl)ethanol] exhibits potent protective activities against several pathogeneses. In this study, we evaluated the protective effect of tyrosol against 1-methyl-4-phenylpyridinium (MPP(+))-induced CATH.a neuron cell death. Tyrosol dose-dependently protected CATH.a cells from MPP(+)-induced cell death and the protection was more apparent after prolong incubation (48h). The data showed that tyrosol treatment suppressed the reduction of phospho-tyrosine hydroxylase level in CATH.a cells. Further, the compound repressed MPP(+)-induced depletion of mitochondrial membrane potential (Δψm) and thereby maintained intracellular ATP production in the cell. The cellular signalling pathway studies revealed that tyrosol protected CATH.a cells from MPP(+)-induced apoptotic signalling, most likely via activation of PI3K/Akt signalling pathway along with up-regulation of anti-oxidative enzymes (SOD-1 and SOD-2) and DJ-1 protein in the cell. Collectively, present study demonstrates that tyrosol significantly protects dopaminergic neurons from MPP(+)-induced degradation, and reveals potential neuroprotective mechanism of tyrosol.

  6. Global and fine information coded by single neurons in the temporal visual cortex

    NASA Astrophysics Data System (ADS)

    Sugase, Yasuko; Yamane, Shigeru; Ueno, Shoogo; Kawano, Kenji

    1999-08-01

    When we see a person's face, we can easily recognize their species, individual identity and emotional state. How does the brain represent such complex information? A substantial number of neurons in the macaque temporal cortex respond to faces. However, the neuronal mechanisms underlying the processing ofcomplex information are not yet clear. Here we recorded the activity of single neurons in the temporal cortex of macaque monkeys while presenting visual stimuli consisting of geometric shapes, and monkey and human faces with various expressions. Information theory was used to investigate how well the neuronal responses could categorize the stimuli. We found that single neurons conveyed two different scales of facial information intheir firing patterns, starting at different latencies. Global information, categorizing stimuli as monkey faces, human faces or shapes, was conveyed in the earliest part of the responses. Fineinformation about identity or expression was conveyed later,beginning on average 51ms after global information. We speculate that global information could be used as a `header' to prepare destination areas for receiving more detailed information.

  7. Spatio-temporal characterization imaging of Ca2+ oscillations in rat hippocampal neurons

    NASA Astrophysics Data System (ADS)

    Zhang, Zhihong; Lu, Jinling; Zhou, Wei; Liu, Rengang; Zeng, Shaoqun; Luo, Qingming

    2001-08-01

    Ca2+ is the most common signal transduction element in cells and plays critical rolls in neuronal development and plasticity. Ca2+ signals encode information in their oscillation frequency or amplitude and response time to regular cellular function. In this study, in order to reveal the spatio-temporal characterization of Ca2+ oscillations in rat hippocampal neurons, two kinds of Ca2+ fluorescent probes, yellow cameleons 2.1 (YC2.1) and Fluo-3, were used to monitor the change of the intracellular free Ca2+ concentration (]Ca2+[i). Spontaneous Ca2+ oscillations and glutamate elicited Ca2+ oscillations were observed with multi-photon excitation laser scan microscope (MPELSM) and confocal laser scan microscope (CLSM). The observation showed that the spatio- temporal characterization of either spontaneous or glutamate provoked Ca2+ oscillations had difference between the neurites and somata in individual nerons, especially in some distal end of neurites. The result indicated that Ca2+ oscillations were most important signal transduction pattern in neuronal development and activation. The spatio-temporal characterization of difference of Ca2+ signals between the distal endo of neurites and the somata might be associated with the distribution of ionotropic receptor and metabotropic glutamate receptors, and Ca2+ response mechanism mediated by two kinds of glutamate receptor. Ca2+ signal elicited by glutamate in the distal end of neurites appeared more complex and generated faster than that in the somata. It was suggested that Ca2+ signal in glutamate stimulated hippacamal neurons first generated from the distal end of neurites and then transduted to the somata. The complicated Ca2+ signal characterization in the distal end of neurites might be associated with neuronal activitation, neurotransmitter releasing, and other functions of neurons.

  8. Balance between excitation and inhibition controls the temporal organization of neuronal avalanches.

    PubMed

    Lombardi, F; Herrmann, H J; Perrone-Capano, C; Plenz, D; de Arcangelis, L

    2012-06-01

    Neuronal avalanches, measured in vitro and in vivo, exhibit a robust critical behavior. Their temporal organization hides the presence of correlations. Here we present experimental measurements of the waiting time distribution between successive avalanches in the rat cortex in vitro. This exhibits a nonmonotonic behavior not usually found in other natural processes. Numerical simulations provide evidence that this behavior is a consequence of the alternation between states of high and low activity, named up and down states, leading to a balance between excitation and inhibition controlled by a single parameter. During these periods, both the single neuron state and the network excitability level, keeping memory of past activity, are tuned by homeostatic mechanisms.

  9. Pheromone responsiveness threshold depends on temporal integration by antennal lobe projection neurons

    PubMed Central

    Tabuchi, Masashi; Sakurai, Takeshi; Mitsuno, Hidefumi; Namiki, Shigehiro; Minegishi, Ryo; Shiotsuki, Takahiro; Uchino, Keiro; Sezutsu, Hideki; Tamura, Toshiki; Haupt, Stephan Shuichi; Nakatani, Kei; Kanzaki, Ryohei

    2013-01-01

    The olfactory system of male moths has an extreme sensitivity with the capability to detect and recognize conspecific pheromones dispersed and greatly diluted in the air. Just 170 molecules of the silkmoth (Bombyx mori) sex pheromone bombykol are sufficient to induce sexual behavior in the male. However, it is still unclear how the sensitivity of olfactory receptor neurons (ORNs) is relayed through the brain to generate high behavioral responsiveness. Here, we show that ORN activity that is subthreshold in terms of behavior can be amplified to suprathreshold levels by temporal integration in antennal lobe projection neurons (PNs) if occurring within a specific time window. To control ORN inputs with high temporal resolution, channelrhodopsin-2 was genetically introduced into bombykol-responsive ORNs. Temporal integration in PNs was only observed for weak inputs, but not for strong inputs. Pharmacological dissection revealed that GABAergic mechanisms inhibit temporal integration of strong inputs, showing that GABA signaling regulates PN responses in a stimulus-dependent fashion. Our results show that boosting of the PNs’ responses by temporal integration of olfactory information occurs specifically near the behavioral threshold, effectively defining the lower bound for behavioral responsiveness. PMID:24006366

  10. Neuronal and perceptual differences in the temporal processing of darks and lights.

    PubMed

    Komban, Stanley Jose; Kremkow, Jens; Jin, Jianzhong; Wang, Yushi; Lashgari, Reza; Li, Xiaobing; Zaidi, Qasim; Alonso, Jose-Manuel

    2014-04-02

    Visual information is mediated by two major thalamic pathways that signal light decrements (OFF) and increments (ON) in visual scenes, the OFF pathway being faster than the ON. Here, we demonstrate that this OFF temporal advantage is transferred to visual cortex and has a correlate in human perception. OFF-dominated cortical neurons in cats responded ∼3 ms faster to visual stimuli than ON-dominated cortical neurons, and dark-mediated suppression in ON-dominated neurons peaked ∼14 ms faster than light-mediated suppression in OFF-dominated neurons. Consistent with the neuronal differences, human observers were 6-14 ms faster at detecting darks than lights and better at discriminating dark than light flickers. Neuronal and perceptual differences both vanished if backgrounds were biased toward darks. Our results suggest that the cortical OFF pathway is faster than the ON pathway at increasing and suppressing visual responses, and these differences have parallels in the human visual perception of lights and darks. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Downregulation of gephyrin in temporal lobe epilepsy neurons in humans and a rat model.

    PubMed

    Fang, Min; Shen, Lan; Yin, Huan; Pan, Yu-Min; Wang, Liang; Chen, Dan; Xi, Zhi-Qin; Xiao, Zheng; Wang, Xue-Feng; Zhou, Sheng-Nian

    2011-10-01

    Gephyrin, which is a postsynaptic scaffolding protein participated in clustering GABA(A) receptors at inhibitory synapses, has been reported to be involved in temporal lobe epilepsy (TLE) recently. Here, we investigate gephyrin protein expression in the temporal lobe epileptic foci in epileptic patients and experimental animals in order to explore the probable relationship between gephyrin expression and TLE. Using immunohistochemistry, immunofluorescence, and western blot analysis, gephyrin expression was examined in 30 human temporal neocortex samples from patients who underwent surgery to treat drug-refractory TLE and 10 histological normal temporal neocortex from the controls. Meanwhile, we investigated the gephyrin expression in the hippocampus and adjacent neocortex from experimental rats on 24 h, 48 h, 1 week, 2 weeks, 1 month, and 2 months postseizure and from control rats. Gephyrin protein was mainly expressed in the membrane and cytoplasm of neurons in temporal lobe epileptic foci in humans and experimental rats. Gephyrin expression was significantly lower in the temporal neocortex of TLE patients compared to the controls. In experimental rats, the expression of gephyrin in temporal lobe was downregulated in epileptic groups compared to the control group. Gephyrin expression gradually decreased during the acute period and the latent period, but then began to increase below the levels seen in controls during the chronic phase. Our findings suggest that gephyrin may be involved in the development of TLE.

  12. Sensitivity of temporal excitation properties to the neuronal element activated by extracellular stimulation.

    PubMed

    Miocinovic, Svjetlana; Grill, Warren M

    2004-01-15

    Measurements of the chronaxies and refractory periods with extracellular stimuli have been used to conclude that large diameter axons are responsible for the effects of deep brain stimulation (DBS). We hypothesized that because action potential initiation by extracellular stimulation occurs in the axons of central nervous system (CNS) neurons, the chronaxies and refractory periods determined using extracellular stimulation would be similar for cells and axons. Computer simulation was used to determine the sensitivity of chronaxie and refractory period to the neural element stimulated. The results demonstrate that chronaxies and refractory periods were dependent on the polarity of the extracellular stimulus and the electrode-to-neuron distance, and indicate that there is little systematic difference in either chronaxies or refractory periods between local cells or axons of passage with extracellular stimulation. This finding points out the difficulty in drawing conclusions regarding which neuronal elements are activated based on extracellular measurements of temporal excitation properties.

  13. Two-population model for medial temporal lobe neurons: The vast majority are almost silent

    NASA Astrophysics Data System (ADS)

    Magyar, Andrew; Collins, John

    2015-07-01

    Recordings in the human medial temporal lobe have found many neurons that respond to pictures (and related stimuli) of just one particular person of those presented. It has been proposed that these are concept cells, responding to just a single concept. However, a direct experimental test of the concept cell idea appears impossible, because it would need the measurement of the response of each cell to enormous numbers of other stimuli. Here we propose a new statistical method for analysis of the data that gives a more powerful way to analyze how close data are to the concept-cell idea. Central to the model is the neuronal sparsity, defined as the total fraction of stimuli that elicit an above-threshold response in the neuron. The model exploits the large number of sampled neurons to give sensitivity to situations where the average response sparsity is much less than one response for the number of presented stimuli. We show that a conventional model where a single sparsity is postulated for all neurons gives an extremely poor fit to the data. In contrast, a model with two dramatically different populations gives an excellent fit to data from the hippocampus and entorhinal cortex. In the hippocampus, one population has 7% of the cells with a 2.6% sparsity. But a much larger fraction (93%) respond to only 0.1% of the stimuli. This can result in an extreme bias in the responsiveness of reported neurons compared with a typical neuron. Finally, we show how to allow for the fact that some identified units correspond to multiple neurons and find that our conclusions at the neural level are quantitatively changed but strengthened, with an even stronger difference between the two populations.

  14. Steroid hormone induction of temporal gene expression in Drosophila brain neuroblasts generates neuronal and glial diversity.

    PubMed

    Syed, Mubarak Hussain; Mark, Brandon; Doe, Chris Q

    2017-04-10

    An important question in neuroscience is how stem cells generate neuronal diversity. During Drosophila embryonic development, neural stem cells (neuroblasts) sequentially express transcription factors that generate neuronal diversity; regulation of the embryonic temporal transcription factor cascade is lineage-intrinsic. In contrast, larval neuroblasts generate longer ~50 division lineages, and currently only one mid-larval molecular transition is known: Chinmo/Imp/Lin-28+ neuroblasts transition to Syncrip+ neuroblasts. Here we show that the hormone ecdysone is required to down-regulate Chinmo/Imp and activate Syncrip, plus two late neuroblast factors, Broad and E93. We show that Seven-up triggers Chinmo/Imp to Syncrip/Broad/E93 transition by inducing expression of the Ecdysone receptor in mid-larval neuroblasts, rendering them competent to respond to the systemic hormone ecdysone. Importantly, late temporal gene expression is essential for proper neuronal and glial cell type specification. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors.

  15. Persistent Single-Neuron Activity during Working Memory in the Human Medial Temporal Lobe.

    PubMed

    Kornblith, Simon; Quian Quiroga, Rodrigo; Koch, Christof; Fried, Itzhak; Mormann, Florian

    2017-04-03

    Working memory is an essential component of human cognition. Persistent activity related to working memory has been reported in many brain areas, including the inferior temporal and prefrontal cortex [1-8]. The medial temporal lobe (MTL) contains "concept cells" that respond invariantly to specific individuals or places whether presented as images, text, or speech [9, 10]. It is unknown, however, whether the MTL also participates in working memory processes. We thus sought to determine whether human MTL neurons respond to images held in working memory. We recorded from patients with chronically intractable epilepsy as they performed a task that required them to remember three or four sequentially presented pictures across a brief delay. 48% of visually selective neurons continued to carry image-specific information after image offset, but most ceased to encode previously presented images after a subsequent presentation of a different image. However, 8% of visually selective neurons encoded previously presented images during a final maintenance period, despite presentation of further images in the intervening interval. Population activity of stimulus-selective neurons predicted behavioral outcome in terms of correct and incorrect responses. These findings indicate that the MTL is part of a brain-wide network for working memory.

  16. 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.

  17. Neuronal correlates of functional magnetic resonance imaging in human temporal cortex

    PubMed Central

    Corina, David P.; Corrigan, Neva; Schoenfield-McNeill, Julie; Poliakov, Andrew; Zamora, Leona; Zanos, Stavros

    2010-01-01

    The relationship between changes in functional magnetic resonance imaging and neuronal activity remains controversial. Data collected during awake neurosurgical procedures for the treatment of epilepsy provided a rare opportunity to examine this relationship in human temporal association cortex. We obtained functional magnetic resonance imaging blood oxygen dependent signals, single neuronal activity and local field potentials from 8 to 300 Hz at 13 temporal cortical sites, from nine subjects, during paired associate learning and control measures. The relation between the functional magnetic resonance imaging signal and the electrophysiologic parameters was assessed in two ways: colocalization between significant changes in these signals on the same paired associate-control comparisons and multiple linear regressions of the electrophysiologic measures on the functional magnetic resonance imaging signal, across all tasks. Significant colocalization was present between increased functional magnetic resonance imaging signals and increased local field potentials power in the 50–250 Hz range. Local field potentials power greater than 100 Hz was also a significant regressor for the functional magnetic resonance imaging signal, establishing this local field potentials frequency range as a neuronal correlate of the functional magnetic resonance imaging signal. There was a trend for a relation between power in some low frequency local field potentials frequencies and the functional magnetic resonance imaging signal, for 8–15 Hz increases in the colocalization analysis and 16–23 Hz in the multiple linear regression analysis. Neither analysis provided evidence for an independent relation to frequency of single neuron activity. PMID:19773355

  18. Auditory and Visual Modulation of Temporal Lobe Neurons in Voice-Sensitive and Association Cortices

    PubMed Central

    Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K.

    2014-01-01

    Effective interactions between conspecific individuals can depend upon the receiver forming a coherent multisensory representation of communication signals, such as merging voice and face content. Neuroimaging studies have identified face- or voice-sensitive areas (Belin et al., 2000; Petkov et al., 2008; Tsao et al., 2008), some of which have been proposed as candidate regions for face and voice integration (von Kriegstein et al., 2005). However, it was unclear how multisensory influences occur at the neuronal level within voice- or face-sensitive regions, especially compared with classically defined multisensory regions in temporal association cortex (Stein and Stanford, 2008). Here, we characterize auditory (voice) and visual (face) influences on neuronal responses in a right-hemisphere voice-sensitive region in the anterior supratemporal plane (STP) of Rhesus macaques. These results were compared with those in the neighboring superior temporal sulcus (STS). Within the STP, our results show auditory sensitivity to several vocal features, which was not evident in STS units. We also newly identify a functionally distinct neuronal subpopulation in the STP that appears to carry the area's sensitivity to voice identity related features. Audiovisual interactions were prominent in both the STP and STS. However, visual influences modulated the responses of STS neurons with greater specificity and were more often associated with congruent voice-face stimulus pairings than STP neurons. Together, the results reveal the neuronal processes subserving voice-sensitive fMRI activity patterns in primates, generate hypotheses for testing in the visual modality, and clarify the position of voice-sensitive areas within the unisensory and multisensory processing hierarchies. PMID:24523543

  19. The Temporal Contribution of the Gbx2 Lineage to Cerebellar Neurons

    PubMed Central

    Hagan, Nellwyn; Guarente, Juliana; Ellisor, Debra; Zervas, Mark

    2017-01-01

    The cerebellum (Cb) is an exquisite structure that controls elaborate motor behaviors and is essential for sensory-motor learning. During development, the Cb is derived from rhombomere 1 (r1). Within this embryonic compartment, precursors in r1 are patterned by signaling cues originating from the isthmus organizer (IsO) and subsequently undergo complex morphogenic movements to establish their final position in the mature Cb. The transcription factor Gbx2 is expressed in the developing Cb and is intimately involved in organizing and patterning the Cb. Nevertheless, how precursors expressing Gbx2 at specific embryonic time points contribute to distinct cell types in the adult Cb is unresolved. In this study, we used Genetic Inducible Fate Mapping (GIFM) to mark Gbx2-expressing precursors with fine temporal resolution and to subsequently track this lineage through embryogenesis. We then determined the terminal neuronal fate of the Gbx2 lineage in the adult Cb. Our analysis demonstrates that the Gbx2 lineage contributes to the Cb with marking over the course of five stages: Embryonic day 7.5 (E7.5) through E11.5. The Gbx2 lineage gives rise to Purkinje cells, granule neurons, and deep cerebellar neurons across these marking stages. Notably, the contribution of the Gbx2 lineage shifts as development proceeds with each marking stage producing a distinct profile of mature neurons in the adult Cb. These findings demonstrate the relationship between the temporal expression of Gbx2 and the terminal cell fate of neurons in the Cb. Based on these results, Gbx2 is critical to Cb development, not only for its well-defined role in positioning and maintaining the IsO, but also for guiding the development of Cb precursors and determining the identity of Cb neurons. PMID:28785208

  20. Neuronal activity in dorsomedial and dorsolateral striatum under the requirement for temporal credit assignment.

    PubMed

    Her, Eun Sil; Huh, Namjung; Kim, Jieun; Jung, Min Whan

    2016-06-01

    To investigate neural processes underlying temporal credit assignment in the striatum, we recorded neuronal activity in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively) of rats performing a dynamic foraging task in which a choice has to be remembered until its outcome is revealed for correct credit assignment. Choice signals appeared sequentially, initially in the DMS and then in the DLS, and they were combined with action value and reward signals in the DLS when choice outcome was revealed. Unlike in conventional dynamic foraging tasks, neural signals for chosen value were elevated in neither brain structure. These results suggest that dynamics of striatal neural signals related to evaluating choice outcome might differ drastically depending on the requirement for temporal credit assignment. In a behavioral context requiring temporal credit assignment, the DLS, but not the DMS, might be in charge of updating the value of chosen action by integrating choice, action value, and reward signals together.

  1. Neuronal activity in dorsomedial and dorsolateral striatum under the requirement for temporal credit assignment

    PubMed Central

    Her, Eun Sil; Huh, Namjung; Kim, Jieun; Jung, Min Whan

    2016-01-01

    To investigate neural processes underlying temporal credit assignment in the striatum, we recorded neuronal activity in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively) of rats performing a dynamic foraging task in which a choice has to be remembered until its outcome is revealed for correct credit assignment. Choice signals appeared sequentially, initially in the DMS and then in the DLS, and they were combined with action value and reward signals in the DLS when choice outcome was revealed. Unlike in conventional dynamic foraging tasks, neural signals for chosen value were elevated in neither brain structure. These results suggest that dynamics of striatal neural signals related to evaluating choice outcome might differ drastically depending on the requirement for temporal credit assignment. In a behavioral context requiring temporal credit assignment, the DLS, but not the DMS, might be in charge of updating the value of chosen action by integrating choice, action value, and reward signals together. PMID:27245401

  2. Low dimensional representation of face space by face-selective inferior temporal neurons.

    PubMed

    Salehi, Sina; Dehaqani, Mohammad-Reza A; Esteky, Hossein

    2017-05-01

    The representation of visual objects in primate brain is distributed and multiple neurons are involved in encoding each object. One way to understand the neural basis of object representation is to estimate the number of neural dimensions that are needed for veridical representation of object categories. In this study, the characteristics of the match between physical-shape and neural representational spaces in monkey inferior temporal (IT) cortex were evaluated. Specifically, we examined how the number of neural dimensions, stimulus behavioral saliency and stimulus category selectivity of neurons affected the correlation between shape and neural representational spaces in IT cortex. Single-unit recordings from monkey IT cortex revealed that there was a significant match between face space and its neural representation at lower neural dimensions, whereas the optimal match for the non-face objects was observed at higher neural dimensions. There was a statistically significant match between the face and neural spaces only in the face-selective neurons, whereas a significant match was observed for non-face objects in all neurons regardless of their category selectivity. Interestingly, the face neurons showed a higher match for the non-face objects than for the faces at higher neural dimensions. The optimal representation of face space in the responses of the face neurons was a low dimensional map that emerged early (~150 ms post-stimulus onset) and was followed by a high dimensional and relatively late (~300 ms) map for the non-face stimuli. These results support a multiplexing function for the face neurons in the representation of very similar shape spaces, but with different dimensionality and timing scales. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Enhanced Actions of Adenosine in Medial Entorhinal Cortex Layer II Stellate Neurons in Temporal Lobe Epilepsy are Mediated via A1 Receptor Activation

    PubMed Central

    Hargus, Nicholas J.; Jennings, Conor; Perez-Reyes, Edward; Bertram, Edward H.; Patel, Manoj K.

    2011-01-01

    Summary Purpose The adenosinergic system is known to exert an inhibitory affect in the brain and as such adenosine has been considered an endogenous anticonvulsant. Entorhinal cortex (EC) layer II neurons, which serve as the primary input to the hippocampus, are spared in temporal lobe epilepsy (TLE) and become hyperexcitable. Since these neurons also express adenosine receptors, the activity of these neurons may be controlled by adenosine, specifically during seizure activity when adenosine levels are thought to rise. In light of this, we determined if the actions of adenosine on medial EC (mEC) layer II stellate neurons are augmented in TLE and by which receptor subtype. Methods Horizontal brain slices were prepared from rats exhibiting spontaneous seizures (TLE) induced by electrical stimulation and compared with age matched control rats. mEC layer II stellate neurons were visually identified and action potentials (AP) evoked by either a series of depolarizing current injection steps or via presynaptic stimulation of mEC deep layers. The effects of adenosine were compared with actions of adenosine A1 and A2A receptor-specific agonists (CPA and CGS 21680) and antagonists (DPCPX and ZM241385) respectively. Immunohistochemical and qPCR techniques were also employed to assess relative adenosine A1 receptor message and expression. Key Findings mEC layer II stellate neurons were hyper-excitable in TLE, evoking a higher frequency of AP's when depolarized and generating bursts of AP's when synaptically stimulated. Adenosine reduced AP frequency and synaptically evoked AP's in a dose dependent manner (500 nM – 100 μM); however, in TLE, the inhibitory actions of adenosine occurred at concentrations that were without affect in control neurons. In both cases, the inhibitory actions of adenosine were mediated via activation of the A1 and not the A2A receptor subtype. qPCR and immunohistochemical experiments revealed an up-regulation of the adenosine A1 mRNA and an

  4. Familiarity breeds plasticity: distinct effects of experience on putative excitatory and inhibitory neurons in inferior temporal cortex.

    PubMed

    Freedman, David J

    2012-04-12

    Primates have a remarkable capacity to recognize a vast array of visual objects, an ability that depends on experience. In this issue of Neuron, Woloszyn and Sheinberg (2012) report that putative excitatory and inhibitory neurons in inferior temporal cortex exhibit distinct influences long-term visual experience.

  5. Spatio-temporal skin strain distributions evoke low variability spike responses in cuneate neurons

    PubMed Central

    Hayward, Vincent; Terekhov, Alexander V.; Wong, Sheng-Chao; Geborek, Pontus; Bengtsson, Fredrik; Jörntell, Henrik

    2014-01-01

    A common method to explore the somatosensory function of the brain is to relate skin stimuli to neurophysiological recordings. However, interaction with the skin involves complex mechanical effects. Variability in mechanically induced spike responses is likely to be due in part to mechanical variability of the transformation of stimuli into spiking patterns in the primary sensors located in the skin. This source of variability greatly hampers detailed investigations of the response of the brain to different types of mechanical stimuli. A novel stimulation technique designed to minimize the uncertainty in the strain distributions induced in the skin was applied to evoke responses in single neurons in the cat. We show that exposure to specific spatio-temporal stimuli induced highly reproducible spike responses in the cells of the cuneate nucleus, which represents the first stage of integration of peripheral inputs to the brain. Using precisely controlled spatio-temporal stimuli, we also show that cuneate neurons, as a whole, were selectively sensitive to the spatial and to the temporal aspects of the stimuli. We conclude that the present skin stimulation technique based on localized differential tractions greatly reduces response variability that is exogenous to the information processing of the brain and hence paves the way for substantially more detailed investigations of the brain's somatosensory system. PMID:24451390

  6. Converging Neuronal Activity in Inferior Temporal Cortex during the Classification of Morphed Stimuli

    PubMed Central

    Akrami, Athena; Liu, Yan; Treves, Alessandro

    2009-01-01

    How does the brain dynamically convert incoming sensory data into a representation useful for classification? Neurons in inferior temporal (IT) cortex are selective for complex visual stimuli, but their response dynamics during perceptual classification is not well understood. We studied IT dynamics in monkeys performing a classification task. The monkeys were shown visual stimuli that were morphed (interpolated) between pairs of familiar images. Their ability to classify the morphed images depended systematically on the degree of morph. IT neurons were selected that responded more strongly to one of the 2 familiar images (the effective image). The responses tended to peak ∼120 ms following stimulus onset with an amplitude that depended almost linearly on the degree of morph. The responses then declined, but remained above baseline for several hundred ms. This sustained component remained linearly dependent on morph level for stimuli more similar to the ineffective image but progressively converged to a single response profile, independent of morph level, for stimuli more similar to the effective image. Thus, these neurons represented the dynamic conversion of graded sensory information into a task-relevant classification. Computational models suggest that these dynamics could be produced by attractor states and firing rate adaptation within the population of IT neurons. PMID:18669590

  7. Spectral-temporal receptive fields of nonlinear auditory neurons obtained using natural sounds.

    PubMed

    Theunissen, F E; Sen, K; Doupe, A J

    2000-03-15

    The stimulus-response function of many visual and auditory neurons has been described by a spatial-temporal receptive field (STRF), a linear model that for mathematical reasons has until recently been estimated with the reverse correlation method, using simple stimulus ensembles such as white noise. Such stimuli, however, often do not effectively activate high-level sensory neurons, which may be optimized to analyze natural sounds and images. We show that it is possible to overcome the simple-stimulus limitation and then use this approach to calculate the STRFs of avian auditory forebrain neurons from an ensemble of birdsongs. We find that in many cases the STRFs derived using natural sounds are strikingly different from the STRFs that we obtained using an ensemble of random tone pips. When we compare these two models by assessing their predictions of neural response to the actual data, we find that the STRFs obtained from natural sounds are superior. Our results show that the STRF model is an incomplete description of response properties of nonlinear auditory neurons, but that linear receptive fields are still useful models for understanding higher level sensory processing, as long as the STRFs are estimated from the responses to relevant complex stimuli.

  8. Mesocortical dopamine neurons operate in distinct temporal domains using multimodal signaling.

    PubMed

    Lavin, Antonieta; Nogueira, Lourdes; Lapish, Christopher C; Wightman, R Mark; Phillips, Paul E M; Seamans, Jeremy K

    2005-05-18

    In vivo extracellular recording studies have traditionally shown that dopamine (DA) transiently inhibits prefrontal cortex (PFC) neurons, yet recent biophysical measurements in vitro indicate that DA enhances the evoked excitability of PFC neurons for prolonged periods. Moreover, although DA neurons apparently encode stimulus salience by transient alterations in firing, the temporal properties of the PFC DA signal associated with various behaviors is often extraordinarily prolonged. The present study used in vivo electrophysiological and electrochemical measures to show that the mesocortical system produces a fast non-DA-mediated postsynaptic response in the PFC that appears to be initiated by glutamate. In contrast, short burst stimulation of mesocortical DA neurons that produced transient (<4 s) DA release in the PFC caused a simultaneous reduction in spontaneous firing (consistent with extracellular in vivo recordings) and a form of DA-induced potentiation in which evoked firing was increased for tens of minutes (consistent with in vitro measurements). We suggest that the mesocortical system might transmit fast signals about reward or salience via corelease of glutamate, whereas the simultaneous prolonged DA-mediated modulation of firing biases the long-term processing dynamics of PFC networks.

  9. Neuronal oscillations and speech perception: critical-band temporal envelopes are the essence

    PubMed Central

    Ghitza, Oded; Giraud, Anne-Lise; Poeppel, David

    2013-01-01

    A recent opinion article (Neural oscillations in speech: do not be enslaved by the envelope. Obleser et al., 2012) questions the validity of a class of speech perception models inspired by the possible role of neuronal oscillations in decoding speech (e.g., Ghitza, 2011; Giraud and Poeppel, 2012). The authors criticize, in particular, what they see as an over-emphasis of the role of temporal speech envelope information, and an over-emphasis of entrainment to the input rhythm while neglecting the role of top-down processes in modulating the entrainment of neuronal oscillations. Here we respond to these arguments, referring to the phenomenological model of Ghitza (2011), taken as a representative of the criticized approach. PMID:23316150

  10. Different Neurons Population Distribution correlates with Topologic-Temporal Dynamic Acoustic Information Flow

    NASA Astrophysics Data System (ADS)

    Riofrio, Walter; Angel Aguilar, Luis

    In this study, we will focus on two aspects of neural interconnections. One is the way in which the information flow is produced, and the other has to do with the neural distribution with specific architectural arrangements in the brain. It is very important to realize that both aspects are related, but it is possible to support in the former that the information flow is not only governed by the number of spikes in the neurons, but by a series of other factors as well. Here we show the role played by GABAergic neurons in acoustic information transmission in the Central Nucleus of Inferior Colliculus (CNIC). We report a neural spatial-temporal cluster distribution, associated with each isofrequency region. With these results, we will shed some light onto the emergence of certain mental properties starting from the neural dynamic interactions.

  11. Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory nerve activity

    PubMed Central

    Wang, Grace I.

    2012-01-01

    The spatio-temporal pattern of auditory nerve (AN) activity, representing the relative timing of spikes across the tonotopic axis, contains cues to perceptual features of sounds such as pitch, loudness, timbre, and spatial location. These spatio-temporal cues may be extracted by neurons in the cochlear nucleus (CN) that are sensitive to relative timing of inputs from AN fibers innervating different cochlear regions. One possible mechanism for this extraction is “cross-frequency” coincidence detection (CD), in which a central neuron converts the degree of coincidence across the tonotopic axis into a rate code by preferentially firing when its AN inputs discharge in synchrony. We used Huffman stimuli (Carney LH. J Neurophysiol 64: 437–456, 1990), which have a flat power spectrum but differ in their phase spectra, to systematically manipulate relative timing of spikes across tonotopically neighboring AN fibers without changing overall firing rates. We compared responses of CN units to Huffman stimuli with responses of model CD cells operating on spatio-temporal patterns of AN activity derived from measured responses of AN fibers with the principle of cochlear scaling invariance. We used the maximum likelihood method to determine the CD model cell parameters most likely to produce the measured CN unit responses, and thereby could distinguish units behaving like cross-frequency CD cells from those consistent with same-frequency CD (in which all inputs would originate from the same tonotopic location). We find that certain CN unit types, especially those associated with globular bushy cells, have responses consistent with cross-frequency CD cells. A possible functional role of a cross-frequency CD mechanism in these CN units is to increase the dynamic range of binaural neurons that process cues for sound localization. PMID:22972956

  12. [Neuronal death in the neocortex of drug resistant temporal lobe epilepsy patients].

    PubMed

    Lorigados Pedre, L; Orozco Suárez, S; Morales Chacón, L; García Maeso, I; Estupiñán Diaz, B; Bender del Busto, J E; Pavón Fuentes, N; Paula Piñero, B; Rocha Arrieta, L

    2008-11-01

    Introduction. Participation of apoptotic death mechanisms in drug resistant temporal lobe epilepsy (DRTLE) is currently under great debate. We have investigated if there is neuronal loss and the immunodetection to different markers in neocortical tissue death in eigth patients with DRTLE. The neocortexes of five patients deceased due to non-neurological causes, paired in age and gender were evaluated as control tissue. Methods. The evaluation of neuronal loss was made by means of a stereological study and with immunohistochemical techniques with the synaptophysin marker. Immunopositivity to different apoptotic markers (annexin V, caspase 3 and 8, bcl-2 and p53) and detection of deoxyribonucleic acid (DNA) fragmentation (TUNEL) were analyzed and double labeling with synaptophysin was performed in every case. The results were evaluated with confocal microscope and analyzed with the Zeiss LSM 5 Image Browser Program, 2.80.1113 (Germany). Results. A statistically significant decrease in the total number of cells (p < 0.05) and the synaptophysin cells+ (p<0.01) in the neocortex (layer IV) of the patients with DRTLE when compared with the control tissue was found. No significant differences were found in the apoptotic markers bcl-2, p53, caspase 3 and 8 for any of the neocortex layers while there was a statistically significant increase in the number of TUNEL cells+ (p<0.05) and annexin V+ (p<0.05) in the neocortical layer IV of the patients. Conclusions. This group of evidence speaks in favor of the existence of an effect on the neuronal number in the neocortex layer IV that may be associated with noncaspase dependent apoptotic death process, without being able to rule out death by necrosis. Key words: Drug resistant temporal lobe epilepsy. Apoptosis. Necrosis. Neuronal loss. Neurología 2008;23(9):555-565.

  13. Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production.

    PubMed

    Zeidán-Chuliá, Fares; Gelain, Daniel Pens; Kolling, Eduardo Antônio; Rybarczyk-Filho, José Luiz; Ambrosi, Priscilla; Terra, Silvia Resende; Pires, André Simões; da Rocha, João Batista Teixeira; Behr, Guilherme Antônio; Moreira, José Cláudio Fonseca

    2013-01-01

    To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or "antioxidative stress"), could be a cause of in vitro toxicity induced by these drugs.

  14. Non-associative Potentiation of Perisomatic Inhibition Alters the Temporal Coding of Neocortical Layer 5 Pyramidal Neurons

    PubMed Central

    Lourenço, Joana; Pacioni, Simone; Rebola, Nelson; van Woerden, Geeske M.; Marinelli, Silvia; DiGregorio, David; Bacci, Alberto

    2014-01-01

    In the neocortex, the coexistence of temporally locked excitation and inhibition governs complex network activity underlying cognitive functions, and is believed to be altered in several brain diseases. Here we show that this equilibrium can be unlocked by increased activity of layer 5 pyramidal neurons of the mouse neocortex. Somatic depolarization or short bursts of action potentials of layer 5 pyramidal neurons induced a selective long-term potentiation of GABAergic synapses (LTPi) without affecting glutamatergic inputs. Remarkably, LTPi was selective for perisomatic inhibition from parvalbumin basket cells, leaving dendritic inhibition intact. It relied on retrograde signaling of nitric oxide, which persistently altered presynaptic GABA release and diffused to inhibitory synapses impinging on adjacent pyramidal neurons. LTPi reduced the time window of synaptic summation and increased the temporal precision of spike generation. Thus, increases in single cortical pyramidal neuron activity can induce an interneuron-selective GABAergic plasticity effectively altering the computation of temporally coded information. PMID:25003184

  15. Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations

    PubMed Central

    Klausberger, Thomas; Somogyi, Peter

    2015-01-01

    In the cerebral cortex, diverse types of neurons form intricate circuits and cooperate in time for the processing and storage of information. Recent advances reveal a spatiotemporal division of labor in cortical circuits, as exemplified in the CA1 hippocampal area. In particular, distinct GABAergic (γ-aminobutyric acid–releasing) cell types subdivide the surface of pyramidal cells and act in discrete time windows, either on the same or on different subcellular compartments. They also interact with glutamatergic pyramidal cell inputs in a domain-specific manner and support synaptic temporal dynamics, network oscillations, selection of cell assemblies, and the implementation of brain states. The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior. PMID:18599766

  16. Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice.

    PubMed

    Kim, Young-Cho; Han, Sang-Woo; Alberico, Stephanie L; Ruggiero, Rafael N; De Corte, Benjamin; Chen, Kuan-Hua; Narayanan, Nandakumar S

    2017-01-09

    Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson's disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigated whether these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction. We report three main results. First, both PD patients and mice with ventral tegmental area (VTA) dopamine depletion had attenuated delta activity (1-4 Hz) in the medial frontal cortex (MFC) during interval timing. Second, we found that optogenetically stimulating MFC D1DR neurons could increase ramping activity among MFC neurons. Finally, stimulating MFC D1DR neurons specifically at delta frequencies (2 Hz) compensated for deficits in temporal control of action caused by VTA dopamine depletion. Our results suggest that cortical networks can be targeted by frequency-specific brain stimulation to improve dopamine-dependent cognitive processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Disparity-based coding of three-dimensional surface orientation by macaque middle temporal neurons.

    PubMed

    Nguyenkim, Jerry D; DeAngelis, Gregory C

    2003-08-06

    Gradients of binocular disparity across the visual field provide a potent cue to the three-dimensional (3-D) orientation of surfaces in a scene. Neurons selective for 3-D surface orientation defined by disparity gradients have recently been described in parietal cortex, but little is known about where and how this selectivity arises within the visual pathways. Because the middle temporal area (MT) has previously been implicated in depth perception, we tested whether MT neurons could signal the 3-D orientation (as parameterized by tilt and slant) of planar surfaces that were depicted by random-dot stereograms containing a linear gradient of horizontal disparities. We find that many MT neurons are tuned for 3-D surface orientation, and that tilt and slant generally have independent effects on MT responses. This separable coding of tilt and slant is reminiscent of the joint coding of variables in other areas (e.g., orientation and spatial frequency in V1). We show that tilt tuning remains unchanged when all coherent motion is removed from the visual stimuli, indicating that tilt selectivity is not a byproduct of 3-D velocity coding. Moreover, tilt tuning is typically insensitive to changes in the mean disparity (depth) of gradient stimuli, indicating that tilt tuning cannot be explained by conventional tuning for frontoparallel disparities. Finally, we explore the receptive field mechanisms underlying selectivity for 3-D surface orientation, and we show that tilt tuning arises through heterogeneous disparity tuning within the receptive fields of MT neurons. Our findings show that MT neurons carry high-level signals about 3-D surface structure, in addition to coding retinal image velocities.

  18. Stereological study of pyramidal neurons in the human superior temporal gyrus from childhood to adulthood

    PubMed Central

    Barger, Nicole; Sheley, Matthew F.; Schumann, Cynthia M.

    2014-01-01

    The association cortex of the superior temporal gyrus (STG) is implicated in complex social and linguistic functions. As such, reliable methods for quantifying cellular variation in this region could greatly benefit researchers interested in addressing the cellular correlates of typical and atypical function associated with these critical cognitive abilities. To facilitate this task, we first present a general set of cytoarchitectonic criteria targeted specifically toward stereological analyses of thick, Nissl stained sections for the homotypical cortex of the STG, referred to, here, as BA22/TA. Secondly, we use the optical fractionator to estimate pyramidal neuron number and the nucleator for pyramidal somal and nuclear volume to investigate the influence of age and sex on these parameters and to set a typically developing baseline for future comparisons. In 11 typically developing cases aged 4-48 years, the most distinguishing features of BA22/TA were the presence of distinct granular layers, a prominent, jagged layer IIIc, and a distinctly staining VIa. The average number of neurons was 91 ± 15 million, volume of pyramidal soma, 1,512 μm3, and nuclear volume, 348 μm3. We found no correlation with age and neuron number. In contrast, pyramidal somal and nuclear volume were both negatively correlated and linearly associated with age in regression analyses. We found no significant sex differences. Overall, the data support the idea that postnatal neuron numbers are relatively stable through development but also suggest that neuronal volume may be subject to important developmental variation. Both measures are critical variables in the study of developmental neuropathology. PMID:25556320

  19. Decreased Neuronal Differentiation of Newly Generated Cells Underlies Reduced Hippocampal Neurogenesis in Chronic Temporal Lobe Epilepsy

    PubMed Central

    Hattiangady, Bharathi; Shetty, Ashok K.

    2009-01-01

    Hippocampal neurogenesis declines substantially in chronic temporal lobe epilepsy (TLE). However, it is unclear whether this decline is linked to altered production of new cells and/or diminished survival and neuronal fate-choice decision of newly born cells. We quantified different components of hippocampal neurogenesis in rats exhibiting chronic TLE. Through intraperitoneal administration of 5'-bromodeoxyuridine (BrdU) for 12 days, we measured numbers of newly born cells in the subgranular zone-granule cell layer (SGZ-GCL) at 24 hours and 2.5 months post-BrdU administration. Furthermore, the differentiation of newly added cells into neurons and glia was quantified via dual immunofluorescence for BrdU and various markers of neurons and glia. Addition of new cells to the SGZ-GCL over 12 days was comparable between the chronically epileptic hippocampus and the age-matched intact hippocampus. Furthermore, comparison of BrdU+ cells measured at 24 hours and 2.5 months post-BrdU administration revealed similar survival of newly born cells between the two groups. However, only 4-5% of newly born cells (i.e. BrdU+ cells) differentiated into neurons in the chronically epileptic hippocampus, in comparison to 73-80% of such cells exhibiting neuronal differentiation in the intact hippocampus. Moreover, differentiation of newly born cells into S-100β+ astrocytes or NG2+ oligodendrocyte progenitors increased to ~79% in the chronically epileptic hippocampus from ~25% observed in the intact hippocampus. Interestingly, the extent of proliferation of astrocytes and microglia (identified through Ki-67 & S-100β and Ki-67 & OX-42 dual immunofluorescence) in the SGZ-GCL was similar between the chronically epileptic hippocampus and the age-matched intact hippocampus, implying that the proliferation of neural stem/progenitor cells in the SGZ-GCL of the chronically epileptic hippocampus was not obscured by an increased division of glia. Thus, severely diminished DG neurogenesis in

  20. Species specificity of temporal processing in the auditory midbrain of gray treefrogs: long-interval neurons.

    PubMed

    Hanson, Jessica L; Rose, Gary J; Leary, Christopher J; Graham, Jalina A; Alluri, Rishi K; Vasquez-Opazo, Gustavo A

    2016-01-01

    In recently diverged gray treefrogs (Hyla chrysoscelis and H. versicolor), advertisement calls that differ primarily in pulse shape and pulse rate act as an important premating isolation mechanism. Temporally selective neurons in the anuran inferior colliculus may contribute to selective behavioral responses to these calls. Here we present in vivo extracellular and whole-cell recordings from long-interval-selective neurons (LINs) made during presentation of pulses that varied in shape and rate. Whole-cell recordings revealed that interplay between excitation and inhibition shapes long-interval selectivity. LINs in H. versicolor showed greater selectivity for slow-rise pulses, consistent with the slow-rise pulse characteristics of their calls. The steepness of pulse-rate tuning functions, but not the distributions of best pulse rates, differed between the species in a manner that depended on whether pulses had slow or fast-rise shape. When tested with stimuli representing the temporal structure of the advertisement calls of H. chrysoscelis or H. versicolor, approximately 27 % of LINs in H. versicolor responded exclusively to the latter stimulus type. The LINs of H. chrysoscelis were less selective. Encounter calls, which are produced at similar pulse rates in both species (≈5 pulses/s), are likely to be effective stimuli for the LINs of both species.

  1. Improved two-photon imaging of living neurons in brain tissue through temporal gating

    PubMed Central

    Gautam, Vini; Drury, Jack; Choy, Julian M. C.; Stricker, Christian; Bachor, Hans-A.; Daria, Vincent R.

    2015-01-01

    We optimize two-photon imaging of living neurons in brain tissue by temporally gating an incident laser to reduce the photon flux while optimizing the maximum fluorescence signal from the acquired images. Temporal gating produces a bunch of ~10 femtosecond pulses and the fluorescence signal is improved by increasing the bunch-pulse energy. Gating is achieved using an acousto-optic modulator with a variable gating frequency determined as integral multiples of the imaging sampling frequency. We hypothesize that reducing the photon flux minimizes the photo-damage to the cells. Our results, however, show that despite producing a high fluorescence signal, cell viability is compromised when the gating and sampling frequencies are equal (or effectively one bunch-pulse per pixel). We found an optimum gating frequency range that maintains the viability of the cells while preserving a pre-set fluorescence signal of the acquired two-photon images. The neurons are imaged while under whole-cell patch, and the cell viability is monitored as a change in the membrane’s input resistance. PMID:26504651

  2. Age-related primary cochlear neuronal degeneration in human temporal bones.

    PubMed

    Makary, Chadi A; Shin, Jennifer; Kujawa, Sharon G; Liberman, M Charles; Merchant, Saumil N

    2011-12-01

    In cases of acquired sensorineural hearing loss, death of cochlear neurons is thought to arise largely as a result of sensory-cell loss. However, recent studies of acoustic overexposure report massive degeneration of the cochlear nerve despite complete hair cell survival (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). To assess the primary loss of spiral ganglion cells (SGCs) in human ears, neuronal counts were performed in 100 temporal bones from 100 individuals, aged newborn to 100 years, selected to include only cases with a normal population of inner and outer hair cells. Ganglion cell counts declined at a mean rate of 100 cells per year of life. There were no significant gender or inter-aural differences, and a slight increase in degeneration in the basal turn re upper turns was not statistically significant. The age-related decline in SGCs was significantly less than that in prior studies that included ears with hair cell loss (Otte et al., Laryngoscope 88:1231-1246, 1978), but significantly more than for analogous data on vestibular ganglion cells in cases without vestibular hair cell loss (Velazquez-Villasenor et al., Ann Otol Rhinol Laryngol Suppl 181:14-19, 2000). The age-related decline in SGC counts may contribute to the well-known decline in hearing-in-noise performance, and the data will help in interpretation of histopathological findings from temporal bones with known otologic disease.

  3. Analysis of noise-induced temporal correlations in neuronal spike sequences

    NASA Astrophysics Data System (ADS)

    Reinoso, José A.; Torrent, M. C.; Masoller, Cristina

    2016-11-01

    We investigate temporal correlations in sequences of noise-induced neuronal spikes, using a symbolic method of time-series analysis. We focus on the sequence of time-intervals between consecutive spikes (inter-spike-intervals, ISIs). The analysis method, known as ordinal analysis, transforms the ISI sequence into a sequence of ordinal patterns (OPs), which are defined in terms of the relative ordering of consecutive ISIs. The ISI sequences are obtained from extensive simulations of two neuron models (FitzHugh-Nagumo, FHN, and integrate-and-fire, IF), with correlated noise. We find that, as the noise strength increases, temporal order gradually emerges, revealed by the existence of more frequent ordinal patterns in the ISI sequence. While in the FHN model the most frequent OP depends on the noise strength, in the IF model it is independent of the noise strength. In both models, the correlation time of the noise affects the OP probabilities but does not modify the most probable pattern.

  4. Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity.

    PubMed

    Bernstein, Hans-Gert; Trübner, Kurt; Krebs, Philipp; Dobrowolny, Henrik; Bielau, Hendrik; Steiner, Johann; Bogerts, Bernhard

    2014-01-01

    Heroin is one of the most dangerous drugs of abuse, which may exert various neurotoxic actions on the brain (such as gray matter loss, neuronal apoptosis, mitochondrial dysfunction, synaptic defects, depression of adult neurogenensis, as well as development of spongiform leucoencephalopathy). Some of these toxic effects are probably mediated by the gas nitric oxide (NO). We studied by morphometric analysis the numerical density of neurons expressing neuronal nitric oxide synthase (nNOS) in cortical and hypothalamic areas of eight heroin overdose victims and nine matched controls. Heroin addicts showed significantly increased numerical densities of nNOS immunoreactive cells in the right temporal cortex and the left paraventricular nucleus. Remarkably, in heroin abusers, but not in controls, we observed not only immunostained interneurons, but also cortical pyramidal cells. Given that increased cellular expression of nNOS was accompanied by elevated NO generation in brains of heroin addicts, these elevated levels of NO might have contributed to some of the known toxic effects of heroin (for example, reduced adult neurogenesis, mitochondrial pathology or disturbances in synaptic functioning).

  5. Multiphasic Temporal Dynamics in Responses of Midbrain Dopamine Neurons to Appetitive and Aversive Stimuli

    PubMed Central

    Fiorillo, Christopher D.; Song, Minryung R.; Yun, Sora R.

    2013-01-01

    The transient response of dopamine neurons has been described as reward prediction error (RPE), with activation or suppression by events that are better or worse than expected, respectively. However, at least a minority of neurons are activated by aversive or high-intensity stimuli, casting doubt on the generality of RPE in describing the dopamine signal. To overcome limitations of previous studies, we studied neuronal responses to a wider variety of high-intensity and aversive stimuli, and we quantified and controlled aversiveness through a choice task in which macaques sacrificed juice to avoid aversive stimuli. Whereas most previous work has portrayed the RPE as a single impulse or “phase,” here we demonstrate its multiphasic temporal dynamics. Aversive or high-intensity stimuli evoked a triphasic sequence of activation-suppression-activation extending over a period of 40–700 ms. The initial activation at short latencies (40–120 ms) reflected sensory intensity.The influence of motivational value became dominant between 150 and 250 ms, with activation in the case of appetitive stimuli, and suppression in the case of aversive and neutral stimuli. The previously unreported late activation appeared to be a modest “rebound” after strong suppression. Similarly, strong activation by reward was often followed by suppression. We suggest that these “rebounds” may result from overcompensation by homeostatic mechanisms in some cells. Our results are consistent with a realistic RPE, which evolves over time through a dynamic balance of excitation and inhibition PMID:23486944

  6. Neuronal Injury, Gliosis, and Glial Proliferation in Two Models of Temporal Lobe Epilepsy.

    PubMed

    Loewen, Jaycie L; Barker-Haliski, Melissa L; Dahle, E Jill; White, H Steve; Wilcox, Karen S

    2016-04-01

    It is estimated that 30%-40% of epilepsy patients are refractory to therapy and animal models are useful for the identification of more efficacious therapeutic agents. Various well-characterized syndrome-specific models are needed to assess their relevance to human seizure disorders and their validity for testing potential therapies. The corneal kindled mouse model of temporal lobe epilepsy (TLE) allows for the rapid screening of investigational compounds, but there is a lack of information as to the specific inflammatory pathology in this model. Similarly, the Theiler murine encephalomyelitis virus (TMEV) model of TLE may prove to be useful for screening, but quantitative assessment of hippocampal pathology is also lacking. We used immunohistochemistry to characterize and quantitate acute neuronal injury and inflammatory features in dorsal CA1 and dentate gyrus regions and in the directly overlying posterior parietal cortex at 2 time points in each of these TLE models. Corneal kindled mice were observed to have astrogliosis, but not microgliosis or neuron cell death. In contrast, TMEV-injected mice had astrogliosis, microgliosis, neuron death, and astrocyte and microglial proliferation. Our results suggest that these 2 animal models might be appropriate for evaluation of distinct therapies for TLE.

  7. Causal links between dorsal medial superior temporal area neurons and multisensory heading perception.

    PubMed

    Gu, Yong; Deangelis, Gregory C; Angelaki, Dora E

    2012-02-15

    The dorsal medial superior temporal area (MSTd) in the extrastriate visual cortex is thought to play an important role in heading perception because neurons in this area are tuned to both optic flow and vestibular signals. MSTd neurons also show significant correlations with perceptual judgments during a fine heading direction discrimination task. To test for a causal link with heading perception, we used microstimulation and reversible inactivation techniques to artificially perturb MSTd activity while monitoring behavioral performance. Electrical microstimulation significantly biased monkeys' heading percepts based on optic flow, but did not significantly impact vestibular heading judgments. The latter result may be due to the fact that vestibular heading preferences in MSTd are more weakly clustered than visual preferences and multiunit tuning for vestibular stimuli is weak. Reversible chemical inactivation, however, increased behavioral thresholds when heading judgments were based on either optic flow or vestibular cues, although the magnitude of the effects was substantially stronger for optic flow. Behavioral deficits in a combined visual/vestibular stimulus condition were intermediate between the single-cue effects. Despite deficits in discrimination thresholds, animals were able to combine visual and vestibular cues near optimally, even after large bilateral muscimol injections into MSTd. Simulations show that the overall pattern of results following inactivation is consistent with a mixture of contributions from MSTd and other areas with vestibular-dominant tuning for heading. Our results support a causal link between MSTd neurons and multisensory heading perception but suggest that other multisensory brain areas also contribute.

  8. Integration of visual and auditory information by superior temporal sulcus neurons responsive to the sight of actions.

    PubMed

    Barraclough, Nick E; Xiao, Dengke; Baker, Chris I; Oram, Mike W; Perrett, David I

    2005-03-01

    Processing of complex visual stimuli comprising facial movements, hand actions, and body movements is known to occur in the superior temporal sulcus (STS) of humans and nonhuman primates. The STS is also thought to play a role in the integration of multimodal sensory input. We investigated whether STS neurons coding the sight of actions also integrated the sound of those actions. For 23% of neurons responsive to the sight of an action, the sound of that action significantly modulated the visual response. The sound of the action increased or decreased the visually evoked response for an equal number of neurons. In the neurons whose visual response was increased by the addition of sound (but not those neurons whose responses were decreased), the audiovisual integration was dependent upon the sound of the action matching the sight of the action. These results suggest that neurons in the STS form multisensory representations of observed actions.

  9. Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

    PubMed Central

    Zeidán-Chuliá, Fares; Kolling, Eduardo Antônio; Rybarczyk-Filho, José Luiz; Ambrosi, Priscilla; Resende Terra, Silvia; Pires, André Simões; da Rocha, João Batista Teixeira; Antônio Behr, Guilherme; Fonseca Moreira, José Cláudio

    2013-01-01

    Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125–2 mg/mL), taurine (1–16 mg/mL), and guarana (3.125–50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5–50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or “antioxidative stress”), could be a cause of in vitro toxicity induced by these drugs. PMID:23766861

  10. Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

    PubMed Central

    Deshpande, Aditi; Bergami, Matteo; Ghanem, Alexander; Conzelmann, Karl-Klaus; Lepier, Alexandra; Götz, Magdalena; Berninger, Benedikt

    2013-01-01

    Identifying the connectome of adult-generated neurons is essential for understanding how the preexisting circuitry is refined by neurogenesis. Changes in the pattern of connectivity are likely to control the differentiation process of newly generated neurons and exert an important influence on their unique capacity to contribute to information processing. Using a monosynaptic rabies virus-based tracing technique, we studied the evolving presynaptic connectivity of adult-generated neurons in the dentate gyrus (DG) of the hippocampus and olfactory bulb (OB) during the first weeks of their life. In both neurogenic zones, adult-generated neurons first receive local connections from multiple types of GABAergic interneurons before long-range projections become established, such as those originating from cortical areas. Interestingly, despite fundamental similarities in the overall pattern of evolution of presynaptic connectivity, there were notable differences with regard to the development of cortical projections: although DG granule neuron input originating from the entorhinal cortex could be traced starting only from 3 to 5 wk on, newly generated neurons in the OB received input from the anterior olfactory nucleus and piriform cortex already by the second week. This early glutamatergic input onto newly generated interneurons in the OB was matched in time by the equally early innervations of DG granule neurons by glutamatergic mossy cells. The development of connectivity revealed by our study may suggest common principles for incorporating newly generated neurons into a preexisting circuit. PMID:23487772

  11. How spiking neurons give rise to a temporal-feature map: From synaptic plasticity to axonal selection

    NASA Astrophysics Data System (ADS)

    Leibold, Christian; Kempter, Richard; Hemmen, J. Leo

    2002-05-01

    A temporal-feature map is a topographic neuronal representation of temporal attributes of phenomena or objects that occur in the outside world. We explain the evolution of such maps by means of a spike-based Hebbian learning rule in conjunction with a presynaptically unspecific contribution in that, if a synapse changes, then all other synapses connected to the same axon change by a small fraction as well. The learning equation is solved for the case of an array of Poisson neurons. We discuss the evolution of a temporal-feature map and the synchronization of the single cells' synaptic structures, in dependence upon the strength of presynaptic unspecific learning. We also give an upper bound for the magnitude of the presynaptic interaction by estimating its impact on the noise level of synaptic growth. Finally, we compare the results with those obtained from a learning equation for nonlinear neurons and show that synaptic structure formation may profit from the nonlinearity.

  12. High spatial and temporal resolution wide-field imaging of neuron activity using quantum NV-diamond

    PubMed Central

    Hall, L. T.; Beart, G. C. G.; Thomas, E. A.; Simpson, D. A.; McGuinness, L. P.; Cole, J. H.; Manton, J. H.; Scholten, R. E.; Jelezko, F.; Wrachtrup, Jörg; Petrou, S.; Hollenberg, L. C. L.

    2012-01-01

    A quantitative understanding of the dynamics of biological neural networks is fundamental to gaining insight into information processing in the brain. While techniques exist to measure spatial or temporal properties of these networks, it remains a significant challenge to resolve the neural dynamics with subcellular spatial resolution. In this work we consider a fundamentally new form of wide-field imaging for neuronal networks based on the nanoscale magnetic field sensing properties of optically active spins in a diamond substrate. We analyse the sensitivity of the system to the magnetic field generated by an axon transmembrane potential and confirm these predictions experimentally using electronically-generated neuron signals. By numerical simulation of the time dependent transmembrane potential of a morphologically reconstructed hippocampal CA1 pyramidal neuron, we show that the imaging system is capable of imaging planar neuron activity non-invasively at millisecond temporal resolution and micron spatial resolution over wide-fields. PMID:22574249

  13. Temporal synchrony and gamma-to-theta power conversion in the dendrites of CA1 pyramidal neurons.

    PubMed

    Vaidya, Sachin P; Johnston, Daniel

    2013-12-01

    Timing is a crucial aspect of synaptic integration. For pyramidal neurons that integrate thousands of synaptic inputs spread across hundreds of microns, it is thus a challenge to maintain the timing of incoming inputs at the axo-somatic integration site. Here we show that pyramidal neurons in the rodent hippocampus use a gradient of inductance in the form of hyperpolarization-activated cation-nonselective (HCN) channels as an active mechanism to counteract location-dependent temporal differences of dendritic inputs at the soma. Using simultaneous multi-site whole-cell recordings complemented by computational modeling, we find that this intrinsic biophysical mechanism produces temporal synchrony of rhythmic inputs in the theta and gamma frequency ranges across wide regions of the dendritic tree. While gamma and theta oscillations are known to synchronize activity across space in neuronal networks, our results identify a new mechanism by which this synchrony extends to activity within single pyramidal neurons with complex dendritic arbors.

  14. High spatial and temporal resolution wide-field imaging of neuron activity using quantum NV-diamond.

    PubMed

    Hall, L T; Beart, G C G; Thomas, E A; Simpson, D A; McGuinness, L P; Cole, J H; Manton, J H; Scholten, R E; Jelezko, F; Wrachtrup, Jörg; Petrou, S; Hollenberg, L C L

    2012-01-01

    A quantitative understanding of the dynamics of biological neural networks is fundamental to gaining insight into information processing in the brain. While techniques exist to measure spatial or temporal properties of these networks, it remains a significant challenge to resolve the neural dynamics with subcellular spatial resolution. In this work we consider a fundamentally new form of wide-field imaging for neuronal networks based on the nanoscale magnetic field sensing properties of optically active spins in a diamond substrate. We analyse the sensitivity of the system to the magnetic field generated by an axon transmembrane potential and confirm these predictions experimentally using electronically-generated neuron signals. By numerical simulation of the time dependent transmembrane potential of a morphologically reconstructed hippocampal CA1 pyramidal neuron, we show that the imaging system is capable of imaging planar neuron activity non-invasively at millisecond temporal resolution and micron spatial resolution over wide-fields.

  15. How Does the Sparse Memory “Engram” Neurons Encode the Memory of a Spatial–Temporal Event?

    PubMed Central

    Guan, Ji-Song; Jiang, Jun; Xie, Hong; Liu, Kai-Yuan

    2016-01-01

    Episodic memory in human brain is not a fixed 2-D picture but a highly dynamic movie serial, integrating information at both the temporal and the spatial domains. Recent studies in neuroscience reveal that memory storage and recall are closely related to the activities in discrete memory engram (trace) neurons within the dentate gyrus region of hippocampus and the layer 2/3 of neocortex. More strikingly, optogenetic reactivation of those memory trace neurons is able to trigger the recall of naturally encoded memory. It is still unknown how the discrete memory traces encode and reactivate the memory. Considering a particular memory normally represents a natural event, which consists of information at both the temporal and spatial domains, it is unknown how the discrete trace neurons could reconstitute such enriched information in the brain. Furthermore, as the optogenetic-stimuli induced recall of memory did not depend on firing pattern of the memory traces, it is most likely that the spatial activation pattern, but not the temporal activation pattern of the discrete memory trace neurons encodes the memory in the brain. How does the neural circuit convert the activities in the spatial domain into the temporal domain to reconstitute memory of a natural event? By reviewing the literature, here we present how the memory engram (trace) neurons are selected and consolidated in the brain. Then, we will discuss the main challenges in the memory trace theory. In the end, we will provide a plausible model of memory trace cell network, underlying the conversion of neural activities between the spatial domain and the temporal domain. We will also discuss on how the activation of sparse memory trace neurons might trigger the replay of neural activities in specific temporal patterns. PMID:27601979

  16. Robust temporal coding of contrast by V1 neurons for transient but not for steady-state stimuli.

    PubMed

    Mechler, F; Victor, J D; Purpura, K P; Shapley, R

    1998-08-15

    We show that spike timing adds to the information content of spike trains for transiently presented stimuli but not for comparable steady-state stimuli, even if the latter elicit transient responses. Contrast responses of 22 single neurons in macaque V1 to periodic presentation of steady-state stimuli (drifting sinusoidal gratings) and transient stimuli (drifting edges) of optimal spatiotemporal parameters were recorded extracellularly. The responses were analyzed for contrast-dependent clustering in spaces determined by metrics sensitive to the temporal structure of spike trains. Two types of metrics, cost-based spike time metrics and metrics based on Fourier harmonics of the response, were used. With both families of metrics, temporal coding of contrast is lacking in responses to drifting sinusoidal gratings of most (simple and complex) V1 neurons. However, two-thirds of all neurons, mostly complex cells, displayed significant temporal coding of contrast for edge stimuli. The Fourier metrics indicated that different response harmonics are partially independent, and their combined use increases information about transient stimuli. Our results demonstrate the importance of stimulus transience for temporal coding. This finding is significant for natural vision because moving edges, which are present in moving object boundaries, and saccades induce transients. We think that an abrupt change in the adapted state of the local visual circuitry triggers the temporal structuring of spike trains in V1 neurons.

  17. Temporal sequence learning in winner-take-all networks of spiking neurons demonstrated in a brain-based device

    PubMed Central

    McKinstry, Jeffrey L.; Edelman, Gerald M.

    2013-01-01

    Animal behavior often involves a temporally ordered sequence of actions learned from experience. Here we describe simulations of interconnected networks of spiking neurons that learn to generate patterns of activity in correct temporal order. The simulation consists of large-scale networks of thousands of excitatory and inhibitory neurons that exhibit short-term synaptic plasticity and spike-timing dependent synaptic plasticity. The neural architecture within each area is arranged to evoke winner-take-all (WTA) patterns of neural activity that persist for tens of milliseconds. In order to generate and switch between consecutive firing patterns in correct temporal order, a reentrant exchange of signals between these areas was necessary. To demonstrate the capacity of this arrangement, we used the simulation to train a brain-based device responding to visual input by autonomously generating temporal sequences of motor actions. PMID:23760804

  18. Synaptic diversity enables temporal coding of coincident multi-sensory inputs in single neurons

    PubMed Central

    Chabrol, François P.; Arenz, Alexander; Wiechert, Martin T.; Margrie, Troy W.; DiGregorio, David A.

    2015-01-01

    The ability of the brain to rapidly process information from multiple pathways is critical for reliable execution of complex sensory-motor behaviors, yet the cellular mechanisms underlying a neuronal representation of multimodal stimuli are poorly understood. Here we explored the possibility that the physiological diversity of mossy fiber (MF) to granule cell (GC) synapses within the mouse vestibulocerebellum may contribute to the processing of coincident multisensory information at the level of individual GCs. We found that the strength and short-term dynamics of individual MF-GC synapses can act as biophysical signatures for primary vestibular, secondary vestibular and visual input pathways. The majority of GCs receive inputs from different modalities, which when co-activated, produced enhanced GC firing rates and distinct first spike latencies. Thus, pathway-specific synaptic response properties permit temporal coding of correlated multisensory input by single GCs, thereby enriching sensory representation and facilitating pattern separation. PMID:25821914

  19. Octopaminergic modulation of temporal frequency tuning of a fly visual motion-sensitive neuron depends on adaptation level

    PubMed Central

    Lüders, Janina; Kurtz, Rafael

    2015-01-01

    Several recent studies in invertebrates as well as vertebrates have demonstrated that neuronal response characteristics of sensory neurons can be profoundly affected by an animal’s locomotor activity. The functional consequences of such state-dependent modulation have been a matter of intense debate. In flies, a particularly interesting finding was that tethered walking or flying causes not only general response enhancement of visual motion-sensitive neurons, but also broadens their temporal frequency tuning towards higher values. However, in other studies such state-dependent alterations of neuronal tuning functions were not found. We hypothesize that these discrepancies were due to different adaptation levels of the motion-sensitive neurons, resulting from the use of different stimulation protocols. This is plausible, because the strength of adaptation during ongoing stimulation was shown to be affected by chlordimeform (CDM), an agonist of the insect neuromodulator octopamine, which mediates state-dependent modulation. Our results show that CDM causes broadening of the temporal frequency tuning of the blowfly’s visual motion-sensitive H1 neuron only in the adapted state, but not prior to the presentation of adapting motion. Thus, our study indicates that seemingly conflicting results on the locomotor state-dependence of neuronal tuning functions are consistent when considering the neurons’ adaptation level. Moreover, it demonstrates that stimulation history has to be considered when the significance of state-dependent modulation of sensory processing is interpreted. PMID:26074790

  20. Effects of category learning on the stimulus selectivity of macaque inferior temporal neurons.

    PubMed

    De Baene, Wouter; Ons, Bart; Wagemans, Johan; Vogels, Rufin

    2008-09-01

    Primates can learn to categorize complex shapes, but as yet it is unclear how this categorization learning affects the representation of shape in visual cortex. Previous studies that have examined the effect of categorization learning on shape representation in the macaque inferior temporal (IT) cortex have produced diverse and conflicting results that are difficult to interpret owing to inadequacies in design. The present study overcomes these issues by recording IT responses before and after categorization learning. We used parameterized shapes that varied along two shape dimensions. Monkeys were extensively trained to categorize the shapes along one of the two dimensions. Unlike previous studies, our paradigm counterbalanced the relevant categorization dimension across animals. We found that categorization learning increased selectivity specifically for the category-relevant stimulus dimension (i.e., an expanded representation of the trained dimension), and that the ratio of within-category response similarities to between-category response similarities increased for the relevant dimension (i.e., category tuning). These small effects were only evident when the learned category-related effects were disentangled from the prelearned stimulus selectivity. These results suggest that shape-categorization learning can induce minor category-related changes in the shape tuning of IT neurons in adults, suggesting that learned, category-related changes in neuronal response mainly occur downstream from IT.

  1. Responses of Neurons in Primary and Inferior Temporal Visual Cortices to Natural Scenes

    NASA Astrophysics Data System (ADS)

    Baddeley, Roland; Abbott, L. F.; Booth, Michael C. A.; Sengpiel, Frank; Freeman, Tobe; Wakeman, Edward A.; Rolls, Edmund T.

    1997-12-01

    The primary visual cortex (V1) is the first cortical area to receive visual input, and inferior temporal (IT) areas are among the last along the ventral visual pathway. We recorded, in area V1 of anaesthetized cats and area IT of awake macaque monkeys, responses of neurons to videos of natural scenes. Responses were analysed to test various hypotheses concerning the nature of neural coding in these two regions. A variety of spike-train statistics were measured including spike-count distributions, interspike interval distributions, coefficients of variation, power spectra, Fano factors and different sparseness measures. All statistics showed non-Poisson characteristics and several revealed self-similarity of the spike trains. Spike-count distributions were approximately exponential in both visual areas for eight different videos and for counting windows ranging from 50 ms to 5 seconds. The results suggest that the neurons maximize their information carrying capacity while maintaining a fixed long-term-average firing rate, or equivalently, minimize their average firing rate for a fixed information carrying capacity.

  2. Auditory forebrain neurons track temporal features of time-warped natural stimuli.

    PubMed

    Maddox, Ross K; Sen, Kamal; Billimoria, Cyrus P

    2014-02-01

    A fundamental challenge for sensory systems is to recognize natural stimuli despite stimulus variations. A compelling example occurs in speech, where the auditory system can recognize words spoken at a wide range of speeds. To date, there have been more computational models for time-warp invariance than experimental studies that investigate responses to time-warped stimuli at the neural level. Here, we address this problem in the model system of zebra finches anesthetized with urethane. In behavioral experiments, we found high discrimination accuracy well beyond the observed natural range of song variations. We artificially sped up or slowed down songs (preserving pitch) and recorded auditory responses from neurons in field L, the avian primary auditory cortex homolog. We found that field L neurons responded robustly to time-warped songs, tracking the temporal features of the stimuli over a broad range of warp factors. Time-warp invariance was not observed per se, but there was sufficient information in the neural responses to reliably classify which of two songs was presented. Furthermore, the average spike rate was close to constant over the range of time warps, contrary to recent modeling predictions. We discuss how this response pattern is surprising given current computational models of time-warp invariance and how such a response could be decoded downstream to achieve time-warp-invariant recognition of sounds.

  3. Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1

    PubMed Central

    Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

    2015-01-01

    The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement—there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

  4. Cytoprotective effects of vitamin E homologues against glutamate-induced cell death in immature primary cortical neuron cultures: Tocopherols and tocotrienols exert similar effects by antioxidant function.

    PubMed

    Saito, Yoshiro; Nishio, Keiko; Akazawa, Yoko Ogawa; Yamanaka, Kazunori; Miyama, Akiko; Yoshida, Yasukazu; Noguchi, Noriko; Niki, Etsuo

    2010-11-30

    Glutamate plays a critical role in pathological cell death within the nervous system. Vitamin E is known to protect cells from glutamate cytotoxicity, either by direct antioxidant action or by indirect nonantioxidant action. Further, α-tocotrienol (α-T3) has been reported to be more effective against glutamate-induced cytotoxicity than α-tocopherol (α-T). To shed more light on the function of vitamin E against glutamate toxicity, the protective effects of eight vitamin E homologues and related compounds, 2,2,5,7,8-pentamethyl-6-chromanol (PMC) and 2-carboxy-2,5,7,8-pentamethyl-6-chromanol (Trolox), against glutamate-induced cytotoxicity on immature primary cortical neurons were examined using different protocols. Glutamate induced the depletion of glutathione and generation of reactive oxygen species and lipid hydroperoxides, leading to cell death. α-, β-, γ-, and δ-T and -T3; PMC; and Trolox all exerted cytoprotective effects against glutamate-induced cytotoxicity, and a longer preincubation time increased both the cellular content and the cytoprotective effects of T more significantly than those of T3, the effect of preincubation being relatively small for T3 and PMC. The protective effect of Trolox was less potent than that of PMC. The cytoprotective effects of α-T and α-T3 corresponded to their intracellular content. Further, lipid peroxidation products were measured after reduction with triphenylphosphine followed by saponification with potassium hydroxide. It was found that glutamate treatment increased the formation of hydroxyeicosatetraenoic acid, hydroxyoctadecadienoic acid, and 8-F(2)-isoprostane 2α, which was suppressed by α-T. This study shows that vitamin E protects cells from glutamate-induced toxicity primarily by direct antioxidant action and that the apparent higher capacity of T3 compared to T is ascribed to the faster uptake of T3 compared to T into the cells. It is suggested that, considering the bioavailability, α-T should be more

  5. The study of the Bithorax-complex genes in patterning CCAP neurons reveals a temporal control of neuronal differentiation by Abd-B

    PubMed Central

    Moris-Sanz, M.; Estacio-Gómez, A.; Sánchez-Herrero, E.; Díaz-Benjumea, F. J.

    2015-01-01

    ABSTRACT During development, HOX genes play critical roles in the establishment of segmental differences. In the Drosophila central nervous system, these differences are manifested in the number and type of neurons generated by each neuroblast in each segment. HOX genes can act either in neuroblasts or in postmitotic cells, and either early or late in a lineage. Additionally, they can be continuously required during development or just at a specific stage. Moreover, these features are generally segment-specific. Lately, it has been shown that contrary to what happens in other tissues, where HOX genes define domains of expression, these genes are expressed in individual cells as part of the combinatorial codes involved in cell type specification. In this report we analyse the role of the Bithorax-complex genes – Ultrabithorax, abdominal-A and Abdominal-B – in sculpting the pattern of crustacean cardioactive peptide (CCAP)-expressing neurons. These neurons are widespread in invertebrates, express CCAP, Bursicon and MIP neuropeptides and play major roles in controlling ecdysis. There are two types of CCAP neuron: interneurons and efferent neurons. Our results indicate that Ultrabithorax and Abdominal-A are not necessary for specification of the CCAP-interneurons, but are absolutely required to prevent the death by apoptosis of the CCAP-efferent neurons. Furthermore, Abdominal-B controls by repression the temporal onset of neuropeptide expression in a subset of CCAP-efferent neurons, and a peak of ecdysone hormone at the end of larval life counteracts this repression. Thus, Bithorax complex genes control the developmental appearance of these neuropeptides both temporally and spatially. PMID:26276099

  6. Pyramidal neurons in the septal and temporal CA1 field of the human and hedgehog tenrec hippocampus.

    PubMed

    Liagkouras, Ioannis; Michaloudi, Helen; Batzios, Christos; Psaroulis, Dimitrios; Georgiadis, Marios; Künzle, Heinz; Papadopoulos, Georgios C

    2008-07-07

    The present study examines comparatively the cellular density of disector-counted/Nissl-stained CA1 pyramidal neurons and the morphometric characteristics (dendritic number/length, spine number/density and Sholl-counted dendritic branch points/20 microm) of the basal and apical dendritic systems of Golgi-impregnated CA1 neurons, in the septal and temporal hippocampus of the human and hedgehog tenrec brain. The obtained results indicate that in both hippocampal parts the cellular density of the CA1 pyramidal neurons is lower in human than in tenrec. However, while the human pyramidal cell density is higher in the septal hippocampal part than in the temporal one, in the tenrec the density of these cells is higher in the temporal part. The dendritic tree of the CA1 pyramidal cells, more developed in the septal than in temporal hippocampus in both species studied, is in general more complex in the human hippocampus. The basal and the apical dendritic systems exhibit species related morphometric differences, while dendrites of different orders exhibit differences in their number and length, and in their spine density. Finally, in both species, as well as hippocampal parts and dendritic systems, changes of dendritic morphometric features along ascending dendritic orders fluctuate in a similar way, as do the number of dendritic branch points in relation to the distance from the neuron soma.

  7. Striatal and Tegmental Neurons Code Critical Signals for Temporal-Difference Learning of State Value in Domestic Chicks

    PubMed Central

    Wen, Chentao; Ogura, Yukiko; Matsushima, Toshiya

    2016-01-01

    To ensure survival, animals must update the internal representations of their environment in a trial-and-error fashion. Psychological studies of associative learning and neurophysiological analyses of dopaminergic neurons have suggested that this updating process involves the temporal-difference (TD) method in the basal ganglia network. However, the way in which the component variables of the TD method are implemented at the neuronal level is unclear. To investigate the underlying neural mechanisms, we trained domestic chicks to associate color cues with food rewards. We recorded neuronal activities from the medial striatum or tegmentum in a freely behaving condition and examined how reward omission changed neuronal firing. To compare neuronal activities with the signals assumed in the TD method, we simulated the behavioral task in the form of a finite sequence composed of discrete steps of time. The three signals assumed in the simulated task were the prediction signal, the target signal for updating, and the TD-error signal. In both the medial striatum and tegmentum, the majority of recorded neurons were categorized into three types according to their fitness for three models, though these neurons tended to form a continuum spectrum without distinct differences in the firing rate. Specifically, two types of striatal neurons successfully mimicked the target signal and the prediction signal. A linear summation of these two types of striatum neurons was a good fit for the activity of one type of tegmental neurons mimicking the TD-error signal. The present study thus demonstrates that the striatum and tegmentum can convey the signals critically required for the TD method. Based on the theoretical and neurophysiological studies, together with tract-tracing data, we propose a novel model to explain how the convergence of signals represented in the striatum could lead to the computation of TD error in tegmental dopaminergic neurons. PMID:27877100

  8. mGluR5 Exerts Cell-Autonomous Influences on the Functional and Anatomical Development of Layer IV Cortical Neurons in the Mouse Primary Somatosensory Cortex

    PubMed Central

    Ballester-Rosado, Carlos J.; Sun, Hao; Huang, Jui-Yen

    2016-01-01

    Glutamate neurotransmission refines synaptic connections to establish the precise neural circuits underlying sensory processing. Deleting metabotropic glutamate receptor 5 (mGluR5) in mice perturbs cortical somatosensory map formation in the primary somatosensory (S1) cortex at both functional and anatomical levels. To examine the cell-autonomous influences of mGluR5 signaling in the morphological and functional development of layer IV spiny stellate glutamatergic neurons receiving sensory input, mGluR5 genetic mosaic mice were generated through in utero electroporation. In the S1 cortex of these mosaic brains, we found that most wild-type neurons were located in barrel rings encircling thalamocortical axon (TCA) clusters while mGluR5 knock-out (KO) neurons were placed in the septal area, the cell-sparse region separating barrels. These KO neurons often displayed a symmetrical dendritic morphology with increased dendritic complexity, in contrast to the polarized pattern of wild-type neurons. The dendritic spine density of mGluR5 KO spiny stellate neurons was significantly higher than in wild-type neurons. Whole-cell electrophysiological recordings detected a significant increase in the frequencies of spontaneous and miniature excitatory postsynaptic events in mGluR5 KO neurons compared with neighboring wild-type neurons. Our mosaic analysis provides strong evidence supporting the cell-autonomous influence of mGluR5 signaling on the functional and anatomical development of cortical glutamatergic neurons. Specifically, mGluR5 is required in cortical glutamatergic neurons for the following processes: (1) the placement of cortical glutamatergic neurons close to TCA clusters; (2) the regulation of dendritic complexity and outgrowth toward TCA clusters; (3) spinogenesis; and (4) tuning of excitatory inputs. SIGNIFICANCE STATEMENT Glutamatergic transmission plays a critical role in cortical circuit formation. Its dysfunction has been proposed as a core factor in the

  9. Temporal Lobe Epilepsy Induces Intrinsic Alterations in Na Channel Gating in Layer II Medial Entorhinal Cortex Neurons

    PubMed Central

    Hargus, Nicholas J.; Merrick, Ellen C.; Nigam, Aradhya; Kalmar, Christopher L.; Baheti, Aparna R.; Bertram, Edward H.; Patel, Manoj K.

    2010-01-01

    Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy involving the limbic structures of the temporal lobe. Layer II neurons of the entorhinal cortex (EC) form the major excitatory input into the hippocampus via the perforant path and consist of non-stellate and stellate neurons. These neurons are spared and hyper-excitable in TLE. The basis for the hyper-excitability is likely multifactorial and may include alterations in intrinsic properties. In a rat model of TLE, medial EC (mEC) non-stellate and stellate neurons had significantly higher action potential (AP) firing frequencies than in control. The increase remained in the presence of synaptic blockers, suggesting intrinsic mechanisms. Since sodium (Na) channels play a critical role in AP generation and conduction we sought to determine if Na channel gating parameters and expression levels were altered in TLE. Na channel currents recorded from isolated mEC TLE neurons revealed increased Na channel conductances, depolarizing shifts in inactivation parameters and larger persistent (INaP) and resurgent (INaR) Na currents. Immunofluorescence experiments revealed increased staining of Nav1.6 within the axon initial segment and Nav1.2 within the cell bodies of mEC TLE neurons. These studies provide support for additional intrinsic alterations within mEC layer II neurons in TLE and implicate alterations in Na channel activity and expression, in part, for establishing the profound increase in intrinsic membrane excitability of mEC layer II neurons in TLE. These intrinsic changes, together with changes in the synaptic network, could support seizure activity in TLE. PMID:20946956

  10. The role of GABAergic inhibition in shaping directional selectivity of bat inferior collicular neurons determined with temporally patterned pulse trains.

    PubMed

    Zhou, X M; Jen, P H-S

    2002-11-01

    This study examined the role of GABAergic inhibition in shaping directional selectivity of neurons in the inferior colliculus of the big brown bat, Eptesicus fuscus. When determined with temporally patterned pulse trains at different pulse repetition rates, 93 inferior colliculus neurons displayed three types of directional selectivity curves. A directionally selective curve always showed a maximum to a certain azimuthal angle (the best angle). A hemifield curve showed a maximum to a range of contralateral azimuthal angles. A non-directional curve did not show a maximum to any particular azimuthal angles. Directional selectivity curves of 42% neurons changed from hemifield or non-directional to directionally selective and the best angles of 16-21% neurons shifted toward the midline with increasing pulse repetition rate of pulse trains. Directional selectivity curves of most (74%) neurons that discharged impulses to each pulse of a pulse train also became sharper with increasing pulse repetition rate of pulse trains. Bicuculline application produced more pronounced broadening of directional selective curves of inferior colliculus neurons at higher than at lower pulse repetition rates. As a result, pulse repetition rate-dependent directional selectivity of inferior colliculus neurons was abolished. Possible mechanisms and biological significance of these findings are discussed.

  11. From perception to action: temporal integrative functions of prefrontal and parietal neurons.

    PubMed

    Quintana, J; Fuster, J M

    1999-01-01

    The dorsolateral prefrontal cortex (DPFC) and the posterior parietal cortex (PPC) are anatomically and functionally interconnected, and have been implicated in working memory and the preparation for behavioral action. To substantiate those functions at the neuronal level, we designed a visuomotor task that dissociated the perceptual and executive aspects of the perception-action cycle in both space and time. In that task, the trial-initiating cue (a color) indicated with different degrees of certainty the direction of the correct manual response 12 s later. We recorded extracellular activity from 258 prefrontal and 223 parietal units in two monkeys performing the task. In the DPFC, some units (memory cells) were attuned to the color of the cue, independent of the response-direction it connoted. Their discharge tended to diminish in the course of the delay between cue and response. In contrast, few color-related units were found in PPC, and these did not show decreasing patterns of delay activity. Other units in both cortices (set cells) were attuned to response-direction and tended to accelerate their firing in anticipation of the response and in proportion to the predictability of its direction. A third group of units was related to the determinacy of the act; their firing was attuned to the certainty with which the animal could predict the correct response, whatever its direction. Cells of the three types were found closely intermingled histologically. These findings further support and define the role of DPFC in executive functions and in the temporal closure of the perception-action cycle. The findings also agree with the involvement of PPC in spatial aspects of visuomotor behavior, and add a temporal integrative dimension to that involvement. Together, the results provide physiological evidence for the role of a prefrontal-parietal network in the integration of perception with action across time.

  12. Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice

    PubMed Central

    Tupal, Srinivasan; Huang, Wei-Hsiang; Picardo, Maria Cristina D; Ling, Guang-Yi; Del Negro, Christopher A; Zoghbi, Huda Y; Gray, Paul A

    2014-01-01

    All motor behaviors require precise temporal coordination of different muscle groups. Breathing, for example, involves the sequential activation of numerous muscles hypothesized to be driven by a primary respiratory oscillator, the preBötzinger Complex, and at least one other as-yet unidentified rhythmogenic population. We tested the roles of Atoh1-, Phox2b-, and Dbx1-derived neurons (three groups that have known roles in respiration) in the generation and coordination of respiratory output. We found that Dbx1-derived neurons are necessary for all respiratory behaviors, whereas independent but coupled respiratory rhythms persist from at least three different motor pools after eliminating or silencing Phox2b- or Atoh1-expressing hindbrain neurons. Without Atoh1 neurons, however, the motor pools become temporally disorganized and coupling between independent respiratory oscillators decreases. We propose Atoh1 neurons tune the sequential activation of independent oscillators essential for the fine control of different muscles during breathing. DOI: http://dx.doi.org/10.7554/eLife.02265.001 PMID:24842997

  13. Temporal integration of cholinergic and GABAergic inputs in isolated insect mushroom body neurons exposes pairing-specific signal processing.

    PubMed

    Raccuglia, Davide; Mueller, Uli

    2014-11-26

    GABAergic modulation of neuronal activity plays a crucial role in physiological processes including learning and memory in both insects and mammals. During olfactory learning in honeybees (Apis mellifera) and Drosophila melanogaster the temporal relation between excitatory cholinergic and inhibitory GABAergic inputs critically affects learning. However, the cellular mechanisms of temporal integration of these antagonistic inputs are unknown. To address this question, we use calcium imaging of isolated honeybee and Drosophila Kenyon cells (KCs), which are targets of cholinergic and GABAergic inputs during olfactory learning. In the whole population of honeybee KCs we find that pairing of acetylcholine (ACh) and γ-aminobutyric acid (GABA) Comment: Please use the greek letter for gamma reduces the ACh-induced calcium influx, and depending on their temporal sequence, induces different forms of neuronal plasticity. After ACh-GABA pairing the calcium influx of a subsequent excitatory stimulus is increased, while GABA-ACh pairing affects the decay time leading to elevated calcium levels during the late phase of a subsequent excitatory stimulus. In an exactly defined subset of Drosophila KCs implicated in learning we find similar pairing-specific differences. Specifically the GABA-ACh pairing splits the KCs in two functional subgroups: one is only weakly inhibited by GABA and shows no neuronal plasticity and the other subgroup is strongly inhibited by GABA and shows elevated calcium levels during the late phase of a subsequent excitatory stimulus. Our findings provide evidence that insect KCs are capable of contributing to temporal processing of cholinergic and GABAergic inputs, which provides a neuronal mechanism of the differential temporal role of GABAergic inhibition during learning. Copyright © 2014 the authors 0270-6474/14/3416086-07$15.00/0.

  14. Presynaptic GABA Receptors Mediate Temporal Contrast Enhancement in Drosophila Olfactory Sensory Neurons and Modulate Odor-Driven Behavioral Kinetics

    PubMed Central

    Demir, Mahmut; Gorur-Shandilya, Srinivas; Kunst, Michael; Nitabach, Michael N.

    2016-01-01

    Contrast enhancement mediated by lateral inhibition within the nervous system enhances the detection of salient features of visual and auditory stimuli, such as spatial and temporal edges. However, it remains unclear how mechanisms for temporal contrast enhancement in the olfactory system can enhance the detection of odor plume edges during navigation. To address this question, we delivered to Drosophila melanogaster flies pulses of high odor intensity that induce sustained peripheral responses in olfactory sensory neurons (OSNs). We use optical electrophysiology to directly measure electrical responses in presynaptic terminals and demonstrate that sustained peripheral responses are temporally sharpened by the combined activity of two types of inhibitory GABA receptors to generate contrast-enhanced voltage responses in central OSN axon terminals. Furthermore, we show how these GABA receptors modulate the time course of innate behavioral responses after odor pulse termination, demonstrating an important role for temporal contrast enhancement in odor-guided navigation. PMID:27588305

  15. The Role of Inhibition in a Computational Model of an Auditory Cortical Neuron during the Encoding of Temporal Information

    PubMed Central

    Bendor, Daniel

    2015-01-01

    In auditory cortex, temporal information within a sound is represented by two complementary neural codes: a temporal representation based on stimulus-locked firing and a rate representation, where discharge rate co-varies with the timing between acoustic events but lacks a stimulus-synchronized response. Using a computational neuronal model, we find that stimulus-locked responses are generated when sound-evoked excitation is combined with strong, delayed inhibition. In contrast to this, a non-synchronized rate representation is generated when the net excitation evoked by the sound is weak, which occurs when excitation is coincident and balanced with inhibition. Using single-unit recordings from awake marmosets (Callithrix jacchus), we validate several model predictions, including differences in the temporal fidelity, discharge rates and temporal dynamics of stimulus-evoked responses between neurons with rate and temporal representations. Together these data suggest that feedforward inhibition provides a parsimonious explanation of the neural coding dichotomy observed in auditory cortex. PMID:25879843

  16. Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity

    PubMed Central

    Serita, Tatsurou; Fukushima, Hotaka; Kida, Satoshi

    2017-01-01

    Transcription factor CREB is believed to play essential roles in the formation of long-term memory (LTM), but not in learning and short-term memory (STM). Surprisingly, we previously showed that transgenic mice expressing a dominant active mutant of CREB (DIEDML) in the forebrain (DIEDML mice) demonstrated enhanced STM and LTM in hippocampal-dependent, rapid, one-trial learning tasks. Here we show that constitutive activation of CREB enhances hippocampal-dependent learning of temporal association in trace fear conditioning and delayed matching-to-place tasks. We then show that in DIEDML mice the apical tuft dendrites of hippocampal CA1 pyramidal neurons, required for temporal association learning, display increased spine density, especially of thin spines and of Homer1-negative spines. In contrast, the basal and apical oblique dendrites of CA1 neurons, required for rapid one-trial learning, show increased density of thin, stubby, and mushroom spines and of Homer1-positive spines. Furthermore, DIEDML mice showed increased dendritic complexity in the proximal portion of apical CA1 dendrites to the soma. In contrast, forebrain overexpression of CaMKIV, leading to enhanced LTM but not STM, show normal learning and CA1 neuron morphology. These findings suggest that dendritic region-specific morphological changes in CA1 neurons by constitutive activation of CREB may contribute to improved learning and STM. PMID:28195219

  17. Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity.

    PubMed

    Serita, Tatsurou; Fukushima, Hotaka; Kida, Satoshi

    2017-02-14

    Transcription factor CREB is believed to play essential roles in the formation of long-term memory (LTM), but not in learning and short-term memory (STM). Surprisingly, we previously showed that transgenic mice expressing a dominant active mutant of CREB (DIEDML) in the forebrain (DIEDML mice) demonstrated enhanced STM and LTM in hippocampal-dependent, rapid, one-trial learning tasks. Here we show that constitutive activation of CREB enhances hippocampal-dependent learning of temporal association in trace fear conditioning and delayed matching-to-place tasks. We then show that in DIEDML mice the apical tuft dendrites of hippocampal CA1 pyramidal neurons, required for temporal association learning, display increased spine density, especially of thin spines and of Homer1-negative spines. In contrast, the basal and apical oblique dendrites of CA1 neurons, required for rapid one-trial learning, show increased density of thin, stubby, and mushroom spines and of Homer1-positive spines. Furthermore, DIEDML mice showed increased dendritic complexity in the proximal portion of apical CA1 dendrites to the soma. In contrast, forebrain overexpression of CaMKIV, leading to enhanced LTM but not STM, show normal learning and CA1 neuron morphology. These findings suggest that dendritic region-specific morphological changes in CA1 neurons by constitutive activation of CREB may contribute to improved learning and STM.

  18. Differences in synaptic and intrinsic properties result in topographic heterogeneity of temporal processing of neurons within the inferior colliculus.

    PubMed

    Yassin, Lina; Pecka, Michael; Kajopoulos, Jasmin; Gleiss, Helge; Li, Lu; Leibold, Christian; Felmy, Felix

    2016-11-01

    The identification and characterization of organization principals is essential for the understanding of neural function of brain areas. The inferior colliculus (IC) represents a midbrain nexus involved in numerous aspects of auditory processing. Likewise, neurons throughout the IC are tuned to a diverse range of specific stimulus features. Yet beyond a topographic arrangement of the cochlea-inherited frequency tuning, the functional organization of the IC is not well understood. Particularly, a common principle that links the diverse tuning characteristics is unknown. Here we used in vitro patch clamp recordings combined with laser-uncaging, and in vivo single cell recordings to study the spatial and functional organization principles of the central IC. We identified a topographic bias of ascending synaptic input timing that is balanced between inhibition and excitation and co-varies with in vivo first-spike latency. This bias was paralleled post-synaptically by differences in biophysical membrane properties and firing patterns, with integrating neurons predominantly found in the dorso-medial part, and coincidence-detector neurons biased to the ventro-lateral IC. Importantly, these cellular and network features translated into distinct temporal processing capabilities irrespectively of the neurons' characteristic frequency. Our data therefore imply that heterogeneity of synaptic inputs, intrinsic properties and temporal processing are functional principles that underlie the spatial organization of the central IC.

  19. Representation of retrieval confidence by single neurons in the human medial temporal lobe

    PubMed Central

    Rutishauser, Ueli; Ye, Shengxuan; Koroma, Matthieu; Tudusciuc, Oana; Ross, Ian B.; Chung, Jeffrey M.; Mamelak, Adam N.

    2015-01-01

    Memory-based decisions are often accompanied by an assessment of choice certainty, but the mechanisms of such confidence judgments remain unknown. We studied the response of 1065 individual neurons in the human hippocampus and amygdala while neurosurgical patients made memory retrieval decisions together with a confidence judgment. Combining behavioral, neuronal and computational analysis, we identified a population of memory-selective (MS) neurons whose activity signaled stimulus familiarity and confidence as assessed by subjective report. In contrast, the activity of visually selective (VS) neurons was not sensitive to memory strength. The groups further differed in response latency, tuning, and extracellular waveforms. The information provided by MS neurons was sufficient for a race model to decide stimulus familiarity and retrieval confidence. Together, this demonstrates a trial-by-trial relationship between a specific group of neurons and declared memory strength in humans. We suggest that VS and MS neurons are a substrate for declarative memories. PMID:26053402

  20. Neuronal Pentraxin 2 predicts medial temporal atrophy and memory decline across the Alzheimer's disease spectrum.

    PubMed

    Swanson, Ashley; Willette, A A

    2016-11-01

    Chronic neuroinflammation is thought to potentiate medial temporal lobe (MTL) atrophy and memory decline in Alzheimer's disease (AD). It has become increasingly important to find novel immunological biomarkers of neuroinflammation or other processes that can track AD development and progression. Our study explored which pro- or anti-inflammatory cerebrospinal fluid (CSF) biomarkers best predicted AD neuropathology over 24months. Using Alzheimer's Disease Neuroimaging Initiative data (N=285), CSF inflammatory biomarkers from mass spectrometry and multiplex panels were screened using stepwise regression, followed up with 50%/50% model retests for validation. Neuronal Pentraxin 2 (NPTX2) and Chitinase-3-like-protein-1 (C3LP1), biomarkers of glutamatergic synaptic plasticity and microglial activation respectively, were the only consistently significant biomarkers selected. Once these biomarkers were selected, linear mixed models were used to analyze their baseline and longitudinal associations with bilateral MTL volume, memory decline, global cognition, and established AD biomarkers including CSF amyloid and tau. Higher baseline NPTX2 levels corresponded to less MTL atrophy [R(2)=0.287, p<0.001] and substantially less memory decline [R(2)=0.560, p<0.001] by month 24. Conversely, higher C3LP1 modestly predicted more MTL atrophy [R(2)=0.083, p<0.001], yet did not significantly track memory decline over time. In conclusion, NPTX2 is a novel pro-inflammatory cytokine that predicts AD-related outcomes better than any immunological biomarker to date, substantially accounting for brain atrophy and especially memory decline. C3LP1 as the microglial biomarker, by contrast, performed modestly and did not predict longitudinal memory decline. This research may advance the current understanding of AD etiopathogenesis, while expanding early diagnostic techniques through the use of novel pro-inflammatory biomarkers, such as NPTX2. Future studies should also see if NPTX2 causally

  1. Spatial and Temporal Distribution of Dopaminergic Neurons during Development in Zebrafish.

    PubMed

    Du, Yuchen; Guo, Qiang; Shan, Minghui; Wu, Yongmei; Huang, Sizhou; Zhao, Haixia; Hong, Huarong; Yang, Ming; Yang, Xi; Ren, Liyi; Peng, Jiali; Sun, Jing; Zhou, Hongli; Li, Shurong; Su, Bingyin

    2016-01-01

    As one of the model organisms of Parkinson's disease (PD) research, the zebrafish has its advantages, such as the 87% homology with human genome and transparent embryos which make it possible to observe the development of dopaminergic neurons in real time. However, there is no midbrain dopaminergic system in zebrafish when compared with mammals, and the location and projection of the dopaminergic neurons are seldom reported. In this study, Vmat2:GFP transgenic zebrafish was used to observe the development and distribution of dopaminergic neurons in real time. We found that diencephalons (DC) 2 and DC4 neuronal populations were detected at 24 h post fertilization (hpf). All DC neuronal populations as well as those in locus coeruleus (LC), raphe nuclei (Ra) and telencephalon were detected at 48 hpf. Axons were detected at 72 hpf. At 96 hpf, all the neuronal populations were detected. For the first time we reported axons from the posterior tubercle (PT) of ventral DC projected to subpallium in vivo. However, when compared with results from whole mount tyrosine hydroxylase (TH) immunofluorescence staining in wild type (WT) zebrafish, we found that DC2 and DC4 neuronal populations were mainly dopaminergic, while DC1, DC3, DC5 and DC6 might not. Neurons in pretectum (Pr) and telencephalon were mainly dopaminergic, while neurons in LC and Ra might be noradrenergic. Our study makes some corrections and modifications on the development, localization and distribution of zebrafish dopaminergic neurons, and provides some experimental evidences for the construction of the zebrafish PD model.

  2. Soy Isoflavones Genistein and Daidzein Exert Anti-Apoptotic Actions via a Selective ER-mediated Mechanism in Neurons following HIV-1 Tat1–86 Exposure

    PubMed Central

    Adams, Sheila M.; Aksenova, Marina V.; Aksenov, Michael Y.; Mactutus, Charles F.; Booze, Rosemarie M.

    2012-01-01

    Background HIV-1 viral protein Tat partially mediates the neural dysfunction and neuronal cell death associated with HIV-1 induced neurodegeneration and neurocognitive disorders. Soy isoflavones provide protection against various neurotoxic insults to maintain neuronal function and thus help preserve neurocognitive capacity. Methodology/Principal Findings We demonstrate in primary cortical cell cultures that 17β-estradiol or isoflavones (genistein or daidzein) attenuate Tat1–86-induced expression of apoptotic proteins and subsequent cell death. Exposure of cultured neurons to the estrogen receptor antagonist ICI 182,780 abolished the anti-apoptotic actions of isoflavones. Use of ERα or ERβ specific antagonists determined the involvement of both ER isoforms in genistein and daidzein inhibition of caspase activity; ERβ selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax. The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced apoptotic signaling. Conclusions/Significance Collectively, our results suggest that soy isoflavones represent an adjunctive therapeutic option with combination anti-retroviral therapy (cART) to preserve neuronal functioning and sustain neurocognitive abilities of HIV-1 infected persons. PMID:22629415

  3. Soy isoflavones genistein and daidzein exert anti-apoptotic actions via a selective ER-mediated mechanism in neurons following HIV-1 Tat(1-86) exposure.

    PubMed

    Adams, Sheila M; Aksenova, Marina V; Aksenov, Michael Y; Mactutus, Charles F; Booze, Rosemarie M

    2012-01-01

    HIV-1 viral protein Tat partially mediates the neural dysfunction and neuronal cell death associated with HIV-1 induced neurodegeneration and neurocognitive disorders. Soy isoflavones provide protection against various neurotoxic insults to maintain neuronal function and thus help preserve neurocognitive capacity. We demonstrate in primary cortical cell cultures that 17β-estradiol or isoflavones (genistein or daidzein) attenuate Tat(1-86)-induced expression of apoptotic proteins and subsequent cell death. Exposure of cultured neurons to the estrogen receptor antagonist ICI 182,780 abolished the anti-apoptotic actions of isoflavones. Use of ERα or ERβ specific antagonists determined the involvement of both ER isoforms in genistein and daidzein inhibition of caspase activity; ERβ selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax. The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced apoptotic signaling. Collectively, our results suggest that soy isoflavones represent an adjunctive therapeutic option with combination anti-retroviral therapy (cART) to preserve neuronal functioning and sustain neurocognitive abilities of HIV-1 infected persons.

  4. Temporal correlation between auditory neurons and the hippocampal theta rhythm induced by novel stimulations in awake guinea pigs.

    PubMed

    Liberman, Tamara; Velluti, Ricardo A; Pedemonte, Marisa

    2009-11-17

    The hippocampal theta rhythm is associated with the processing of sensory systems such as touch, smell, vision and hearing, as well as with motor activity, the modulation of autonomic processes such as cardiac rhythm, and learning and memory processes. The discovery of temporal correlation (phase locking) between the theta rhythm and both visual and auditory neuronal activity has led us to postulate the participation of such rhythm in the temporal processing of sensory information. In addition, changes in attention can modify both the theta rhythm and the auditory and visual sensory activity. The present report tested the hypothesis that the temporal correlation between auditory neuronal discharges in the inferior colliculus central nucleus (ICc) and the hippocampal theta rhythm could be enhanced by changes in sensory stimulation. We presented chronically implanted guinea pigs with auditory stimuli that varied over time, and recorded the auditory response during wakefulness. It was observed that the stimulation shifts were capable of producing the temporal phase correlations between the theta rhythm and the ICc unit firing, and they differed depending on the stimulus change performed. Such correlations disappeared approximately 6 s after the change presentation. Furthermore, the power of the hippocampal theta rhythm increased in half of the cases presented with a stimulation change. Based on these data, we propose that the degree of correlation between the unitary activity and the hippocampal theta rhythm varies with--and therefore may signal--stimulus novelty.

  5. Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance.

    PubMed

    Majaj, Najib J; Hong, Ha; Solomon, Ethan A; DiCarlo, James J

    2015-09-30

    To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT ("face patches") did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. Significance statement: We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a

  6. Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates Accurately Predict Human Core Object Recognition Performance

    PubMed Central

    Hong, Ha; Solomon, Ethan A.; DiCarlo, James J.

    2015-01-01

    To go beyond qualitative models of the biological substrate of object recognition, we ask: can a single ventral stream neuronal linking hypothesis quantitatively account for core object recognition performance over a broad range of tasks? We measured human performance in 64 object recognition tests using thousands of challenging images that explore shape similarity and identity preserving object variation. We then used multielectrode arrays to measure neuronal population responses to those same images in visual areas V4 and inferior temporal (IT) cortex of monkeys and simulated V1 population responses. We tested leading candidate linking hypotheses and control hypotheses, each postulating how ventral stream neuronal responses underlie object recognition behavior. Specifically, for each hypothesis, we computed the predicted performance on the 64 tests and compared it with the measured pattern of human performance. All tested hypotheses based on low- and mid-level visually evoked activity (pixels, V1, and V4) were very poor predictors of the human behavioral pattern. However, simple learned weighted sums of distributed average IT firing rates exactly predicted the behavioral pattern. More elaborate linking hypotheses relying on IT trial-by-trial correlational structure, finer IT temporal codes, or ones that strictly respect the known spatial substructures of IT (“face patches”) did not improve predictive power. Although these results do not reject those more elaborate hypotheses, they suggest a simple, sufficient quantitative model: each object recognition task is learned from the spatially distributed mean firing rates (100 ms) of ∼60,000 IT neurons and is executed as a simple weighted sum of those firing rates. SIGNIFICANCE STATEMENT We sought to go beyond qualitative models of visual object recognition and determine whether a single neuronal linking hypothesis can quantitatively account for core object recognition behavior. To achieve this, we designed a

  7. Color-tuned neurons are spatially clustered according to color preference within alert macaque posterior inferior temporal cortex

    PubMed Central

    Conway, Bevil R.; Tsao, Doris Y.

    2009-01-01

    Large islands of extrastriate cortex that are enriched for color-tuned neurons have recently been described in alert macaque using a combination of functional magnetic resonance imaging (fMRI) and single-unit recording. These millimeter-sized islands, dubbed “globs,” are scattered throughout the posterior inferior temporal cortex (PIT), a swath of brain anterior to area V3, including areas V4, PITd, and posterior TEO. We investigated the micro-organization of neurons within the globs. We used fMRI to identify the globs and then used MRI-guided microelectrodes to test the color properties of single glob cells. We used color stimuli that sample the CIELUV perceptual color space at regular intervals to test the color tuning of single units, and make two observations. First, color-tuned neurons of various color preferences were found within single globs. Second, adjacent glob cells tended to have the same color tuning, demonstrating that glob cells are clustered by color preference and suggesting that they are arranged in color columns. Neurons separated by 50 μm, measured parallel to the cortical sheet, had more similar color tuning than neurons separated by 100 μm, suggesting that the scale of the color columns is <100 μm. These results show that color-tuned neurons in PIT are organized by color preference on a finer scale than the scale of single globs. Moreover, the color preferences of neurons recorded sequentially along a given electrode penetration shifted gradually in many penetrations, suggesting that the color columns are arranged according to a chromotopic map reflecting perceptual color space. PMID:19805195

  8. Color-tuned neurons are spatially clustered according to color preference within alert macaque posterior inferior temporal cortex.

    PubMed

    Conway, Bevil R; Tsao, Doris Y

    2009-10-20

    Large islands of extrastriate cortex that are enriched for color-tuned neurons have recently been described in alert macaque using a combination of functional magnetic resonance imaging (fMRI) and single-unit recording. These millimeter-sized islands, dubbed "globs," are scattered throughout the posterior inferior temporal cortex (PIT), a swath of brain anterior to area V3, including areas V4, PITd, and posterior TEO. We investigated the micro-organization of neurons within the globs. We used fMRI to identify the globs and then used MRI-guided microelectrodes to test the color properties of single glob cells. We used color stimuli that sample the CIELUV perceptual color space at regular intervals to test the color tuning of single units, and make two observations. First, color-tuned neurons of various color preferences were found within single globs. Second, adjacent glob cells tended to have the same color tuning, demonstrating that glob cells are clustered by color preference and suggesting that they are arranged in color columns. Neurons separated by 50 microm, measured parallel to the cortical sheet, had more similar color tuning than neurons separated by 100 microm, suggesting that the scale of the color columns is <100 microm. These results show that color-tuned neurons in PIT are organized by color preference on a finer scale than the scale of single globs. Moreover, the color preferences of neurons recorded sequentially along a given electrode penetration shifted gradually in many penetrations, suggesting that the color columns are arranged according to a chromotopic map reflecting perceptual color space.

  9. Temporal patterning in the responses of gracile and cuneate neurones in the cat to cutaneous vibration.

    PubMed Central

    Ferrington, D G; Horniblow, S; Rowe, M J

    1987-01-01

    1. Recordings were made in decerebrate cats from gracile and cuneate neurones responding to vibration-induced inputs from Pacinian corpuscle (P.c.) receptors of the hind-limb and forelimb footpads. The two groups of neurones were compared, in particular for their capacities for responding to cutaneous vibration with phase-locked impulse patterns. 2. In both nuclei the P.c. neurones were most sensitive to vibration in the range 80 to greater than 600 Hz. Stimulus-response relations were similar for the two groups, as were measures derived from these relations such as response levels, absolute thresholds and the dynamic range (defined as the vibration amplitude range over which responses were graded). 3. At frequencies up to 300-400 Hz, responses for some neurones in both nuclei remained well phase locked to the vibration; however, quantitative analysis using a factorial analysis of variance indicated that the phase locking was poorer in gracile than cuneate neurones. 4. In both nuclei there was marked variability from neurone to neurone in measures of phase locking which may reflect variations in the extent of convergence of P.c. fibres upon different target neurones. For neurones in either nucleus that had comparatively tight phase locking of responses to vibration it is proposed that their output is functionally dominated by one or a few of their convergent P.c. input fibres. PMID:3681710

  10. Differential representation of spectral and temporal information by primary auditory cortex neurons in awake cats: relevance to auditory scene analysis.

    PubMed

    Sakai, Masashi; Chimoto, Sohei; Qin, Ling; Sato, Yu

    2009-04-10

    We investigated how the primary auditory cortex (AI) neurons encode the two major requisites for auditory scene analysis, i.e., spectral and temporal information. Single-unit activities in awake cats AI were studied by presenting 0.5-s-long tone bursts and click trains. First of all, the neurons (n=92) were classified into 3 types based on the time-course of excitatory responses to tone bursts: 1) phasic cells (P-cells; 26%), giving only transient responses; 2) tonic cells (T-cells; 34%), giving sustained responses with little or no adaptation; and 3) phasic-tonic cells (PT-cells; 40%), giving sustained responses with some tendency of adaptation. Other tone-response variables differed among cell types. For example, P-cells showed the shortest latency and smallest spiking jitter while T-cells had the sharpest frequency tuning. PT-cells generally fell in the intermediate between the two extremes. Click trains also revealed between-neuron-type differences for the emergent probability of excitatory responses (P-cells>PT-cells>T-cells) and their temporal features. For example, a substantial fraction of P-cells conducted stimulus-locking responses, but none of the T-cells did. f(r)-dependency characteristics of the stimulus locking resembled that reported for "comodulation masking release," a behavioral model of auditory scene analysis. Each type neurons were omnipresent throughout the AI and none of them showed intrinsic oscillation. These findings suggest that: 1) T-cells preferentially encode spectral information with a rate-place code and 2) P-cells preferentially encode acoustic transients with a temporal code whereby rate-place coded information is potentially bound for scene analysis.

  11. Ability of primary auditory cortical neurons to detect amplitude modulation with rate and temporal codes: neurometric analysis

    PubMed Central

    Johnson, Jeffrey S.; Yin, Pingbo; O'Connor, Kevin N.

    2012-01-01

    Amplitude modulation (AM) is a common feature of natural sounds, and its detection is biologically important. Even though most sounds are not fully modulated, the majority of physiological studies have focused on fully modulated (100% modulation depth) sounds. We presented AM noise at a range of modulation depths to awake macaque monkeys while recording from neurons in primary auditory cortex (A1). The ability of neurons to detect partial AM with rate and temporal codes was assessed with signal detection methods. On average, single-cell synchrony was as or more sensitive than spike count in modulation detection. Cells are less sensitive to modulation depth if tested away from their best modulation frequency, particularly for temporal measures. Mean neural modulation detection thresholds in A1 are not as sensitive as behavioral thresholds, but with phase locking the most sensitive neurons are more sensitive, suggesting that for temporal measures the lower-envelope principle cannot account for thresholds. Three methods of preanalysis pooling of spike trains (multiunit, similar to convergence from a cortical column; within cell, similar to convergence of cells with matched response properties; across cell, similar to indiscriminate convergence of cells) all result in an increase in neural sensitivity to modulation depth for both temporal and rate codes. For the across-cell method, pooling of a few dozen cells can result in detection thresholds that approximate those of the behaving animal. With synchrony measures, indiscriminate pooling results in sensitive detection of modulation frequencies between 20 and 60 Hz, suggesting that differences in AM response phase are minor in A1. PMID:22422997

  12. Combined extrinsic and intrinsic manipulations exert complementary neuronal enrichment in embryonic rat neural precursor cultures: an in vitro and in vivo analysis.

    PubMed

    Furmanski, Orion; Gajavelli, Shyam; Lee, Jeung Woon; Collado, Maria E; Jergova, Stanislava; Sagen, Jacqueline

    2009-07-01

    Numerous central nervous system (CNS) disorders share a common pathology in dysregulation of gamma-aminobutyric acid (GABA) inhibitory signaling. Transplantation of GABA-releasing cells at the site of disinhibition holds promise for alleviating disease symptoms with fewer side effects than traditional drug therapies. We manipulated fibroblast growth factor (FGF)-2 deprivation and mammalian achaete-scute homolog (MASH)1 transcription factor levels in an attempt to amplify the default GABAergic neuronal fate in cultured rat embryonic neural precursor cells (NPCs) for use in transplantation studies. Naïve and MASH1 lentivirus-transduced NPCs were maintained in FGF-2 or deprived of FGF-2 for varying lengths of time. Immunostaining and quantitative analysis showed that GABA- and beta-III-tubulin-immunoreactive cells generally decreased through successive passages, suggesting a loss of neurogenic potential in rat neurospheres expanded in vitro. However, FGF-2 deprivation resulted in a small, but significantly increased population of GABAergic cells derived from passaged neurospheres. In contrast to naïve and GFP lentivirus-transduced clones, MASH1 transduction resulted in increased bromodeoxyuridine (BrdU) incorporation and clonal colony size. Western blotting showed that MASH1 overexpression and FGF-2 deprivation additively increased beta-III-tubulin and decreased cyclic nucleotide phosphodiesterase (CNPase) expression, whereas FGF-2 deprivation alone attenuated glial fibrillary acidic protein (GFAP) expression. These results suggest that low FGF-2 signaling and MASH1 activity can operate in concert to enrich NPC cultures for a GABA neuronal phenotype. When transplanted into the adult rat spinal cord, this combination also yielded GABAergic neurons. These findings indicate that, even for successful utilization of the default GABAergic neuronal precursor fate, a combination of both extrinsic and intrinsic manipulations will likely be necessary to realize the full

  13. Neuronal cell fate specification by the molecular convergence of different spatio-temporal cues on a common initiator terminal selector gene

    PubMed Central

    Stratmann, Johannes

    2017-01-01

    The extensive genetic regulatory flows underlying specification of different neuronal subtypes are not well understood at the molecular level. The Nplp1 neuropeptide neurons in the developing Drosophila nerve cord belong to two sub-classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1 neurons are specified by spatial cues; the Hox homeotic network and GATA factor grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp neurons that activate a common terminal selector feedforward cascade of col -> ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1 neurons, and find that the cis-regulatory organization of col functions as an integratory node for the different spatio-temporal combinatorial codes. These findings may provide a logical framework for addressing spatio-temporal control of neuronal sub-type specification in other systems. PMID:28414802

  14. Spatial and Temporal Distribution of Dopaminergic Neurons during Development in Zebrafish

    PubMed Central

    Du, Yuchen; Guo, Qiang; Shan, Minghui; Wu, Yongmei; Huang, Sizhou; Zhao, Haixia; Hong, Huarong; Yang, Ming; Yang, Xi; Ren, Liyi; Peng, Jiali; Sun, Jing; Zhou, Hongli; Li, Shurong; Su, Bingyin

    2016-01-01

    As one of the model organisms of Parkinson’s disease (PD) research, the zebrafish has its advantages, such as the 87% homology with human genome and transparent embryos which make it possible to observe the development of dopaminergic neurons in real time. However, there is no midbrain dopaminergic system in zebrafish when compared with mammals, and the location and projection of the dopaminergic neurons are seldom reported. In this study, Vmat2:GFP transgenic zebrafish was used to observe the development and distribution of dopaminergic neurons in real time. We found that diencephalons (DC) 2 and DC4 neuronal populations were detected at 24 h post fertilization (hpf). All DC neuronal populations as well as those in locus coeruleus (LC), raphe nuclei (Ra) and telencephalon were detected at 48 hpf. Axons were detected at 72 hpf. At 96 hpf, all the neuronal populations were detected. For the first time we reported axons from the posterior tubercle (PT) of ventral DC projected to subpallium in vivo. However, when compared with results from whole mount tyrosine hydroxylase (TH) immunofluorescence staining in wild type (WT) zebrafish, we found that DC2 and DC4 neuronal populations were mainly dopaminergic, while DC1, DC3, DC5 and DC6 might not. Neurons in pretectum (Pr) and telencephalon were mainly dopaminergic, while neurons in LC and Ra might be noradrenergic. Our study makes some corrections and modifications on the development, localization and distribution of zebrafish dopaminergic neurons, and provides some experimental evidences for the construction of the zebrafish PD model. PMID:27965546

  15. Glycinergic tonic inhibition of hippocampal neurons with depolarizing GABAergic transmission elicits histopathological signs of temporal lobe epilepsy

    PubMed Central

    Eichler, Sabrina A; Kirischuk, Sergei; Jüttner, René; Schafermeier, Philipp K; Legendre, Pascal; Lehmann, Thomas-Nicolas; Gloveli, Tengis; Grantyn, Rosemarie; Meier, Jochen C

    2008-01-01

    An increasing number of epilepsy patients are afflicted with drug-resistant temporal lobe epilepsy (TLE) and require alternative therapeutic approaches. High-affinity glycine receptors (haGlyRs) are functionally adapted to tonic inhibition due to their response to hippocampal ambient glycine, and their synthesis is activity-dependent. Therefore, in our study, we scanned TLE hippocampectomies for expression of haGlyRs and characterized the effects mediated by these receptors using primary hippocampal neurons. Increased haGlyR expression occurred in TLE hippocampi obtained from patients with a severe course of disease. Furthermore, in TLE patients, haGlyR and potassium chloride cotransporter 2 (KCC2) expressions were inversely regulated. To examine this potential causal relationship with respect to TLE histopathology, we established a hippocampal cell culture system utilising tonic inhibition mediated by haGlyRs in response to hippocam-pal ambient glycine and in the context of a high Cl equilibrium potential, as is the case in TLE hippocampal neurons. We showed that hypoactive neurons increase their ratio between glutamatergic and GABAergic synapses, reduce their dendrite length and finally undergo excitotoxicity. Pharmacological dissection of the underlying processes revealed ionotropic glutamate and TrkB receptors as critical mediators between neuronal hypoactivity and the emergence of these TLE-characteristic histopathological signs. Moreover, our results indicate a beneficial role for KCC2, because decreasing the Cl− equilibrium potential by KCC2 expression also rescued hypoactive hippocampal neurons. Thus, our data support a causal relationship between increased haGlyR expression and the emergence of histopathological TLE-characteristic signs, and they establish a pathophysiological role for neuronal hypoactivity in the context of a high Cl− equilibrium potential. PMID:19210758

  16. Unpredictable chronic mild stress exerts anxiogenic-like effects and activates neurons in the dorsal and caudal region and in the lateral wings of the dorsal raphe nucleus.

    PubMed

    Lopes, Danielle A; Lemes, Jéssica A; Melo-Thomas, Liana; Schor, Herbert; de Andrade, José S; Machado, Carla M; Horta-Júnior, José A C; Céspedes, Isabel C; Viana, Milena B

    2016-01-15

    In previous studies, we verified that exposure to unpredictable chronic mild stress (UCMS) facilitates avoidance responses in the elevated T-maze (ETM) and increased Fos-immunoreactivity in different brain structures involved in the regulation of anxiety, including the dorsal raphe (DR). Since, it has been shown that the DR is composed of distinct subpopulations of serotonergic and non-serotonergic neurons, the present study investigated the pattern of activation of these different subnuclei of the region in response to this stress protocol. Male Wistar rats were either unstressed or exposed to the UCMS procedure for two weeks and, subsequently, analyzed for Fos-immunoreactivity (Fos-ir) in serotonergic cells of the DR. To verify if the anxiogenic effects observed in the ETM could be generalized to other anxiety models, a group of animals was also tested in the light/dark transition test after UCMS exposure. Results showed that the UCMS procedure decreased the number of transitions and increased the number of stretched attend postures in the model, an anxiogenic effect. UCMS exposure also increased Fos-ir and the number of double-labeled neurons in the mid-rostral subdivision of the dorsal part of the DR and in the mid-caudal region of the lateral wings. In the caudal region of the DR there was a significant increase in the number of Fos-ir. No significant effects were found in the other DR subnuclei. These results corroborate the idea that neurons of specific subnuclei of the DR regulate anxiety responses and are differently activated by chronic stress exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. The temporal pattern of stimulation determines the extent and duration of MAPK activation in a Caenorhabditis elegans sensory neuron.

    PubMed

    Tomida, Taichiro; Oda, Shigekazu; Takekawa, Mutsuhiro; Iino, Yuichi; Saito, Haruo

    2012-10-16

    The Caenorhabditis elegans ASER sensory neuron is excited when environmental NaCl concentration is decreased. The mitogen-activated protein kinase (MAPK) MPK-1, a homolog of ERK (extracellular signal-regulated kinase), is activated during excitation of ASER sensory neurons. We created and expressed a fluorescence resonance energy transfer (FRET)-based MAPK activity probe in ASER neurons and then exposed the worms to various cyclic patterns of stimulation (changes in NaCl concentration) to monitor the dynamics of MPK-1 activity. We found that the intensity and duration of MPK-1 activity were determined by the temporal pattern of stimulation, namely, a combination of stimulation period length, stimulation duration, and time between stimuli. The complex, nonlinear relationship between stimulation and MPK-1 activation was explained by the properties of intracellular calcium responses upstream of MPK-1. Thus, we visualized the dynamics of MAPK activation in a sensory neuron in living nematodes in response to complex stimuli and present a reporter that can be used in higher eukaryotes to test in silico predictions regarding the MAPK pathway.

  18. Neuronal cell fate diversification controlled by sub-temporal action of Kruppel

    PubMed Central

    Stratmann, Johannes; Gabilondo, Hugo; Benito-Sipos, Jonathan; Thor, Stefan

    2016-01-01

    During Drosophila embryonic nervous system development, neuroblasts express a programmed cascade of five temporal transcription factors that govern the identity of cells generated at different time-points. However, these five temporal genes fall short of accounting for the many distinct cell types generated in large lineages. Here, we find that the late temporal gene castor sub-divides its large window in neuroblast 5–6 by simultaneously activating two cell fate determination cascades and a sub-temporal regulatory program. The sub-temporal program acts both upon itself and upon the determination cascades to diversify the castor window. Surprisingly, the early temporal gene Kruppel acts as one of the sub-temporal genes within the late castor window. Intriguingly, while the temporal gene castor activates the two determination cascades and the sub-temporal program, spatial cues controlling cell fate in the latter part of the 5–6 lineage exclusively act upon the determination cascades. DOI: http://dx.doi.org/10.7554/eLife.19311.001 PMID:27740908

  19. Emergence of oscillations and spatio-temporal coherence states in a continuum-model of excitatory and inhibitory neurons.

    PubMed

    Sabatini, Silvio P; Solari, Fabio; Secchi, Luca

    2005-01-01

    A neural field model of the reaction-diffusion type for the emergence of oscillatory phenomena in visual cortices is proposed. To investigate the joint spatio-temporal oscillatory dynamics in a continuous distribution of excitatory and inhibitory neurons, the coupling among oscillators is modelled as a diffusion process, combined with non-linear point interactions. The model exhibits cooperative activation properties in both time and space, by reacting to volleys of activations at multiple cortical sites with ordered spatio-temporal oscillatory states, similar to those found in the physiological experiments on slow-wave field potentials. The possible use of the resulting spatial distributions of coherent states, as a flexible medium to establish feature association, is discussed.

  20. Presynaptic mitochondria in functionally different motor neurons exhibit similar affinities for Ca2+ but exert little influence as Ca2+ buffers at nerve firing rates in situ

    PubMed Central

    Chouhan, Amit K.; Zhang, Jinhui; Zinsmaier, Konrad E.; Macleod, Gregory T.

    2010-01-01

    Mitochondria accumulate within nerve terminals and support synaptic function, most notably through ATP production. They can also sequester Ca2+ during nerve stimulation, but it is unknown whether this limits presynaptic Ca2+ levels at physiological nerve firing rates. Similarly, it is unclear whether mitochondrial Ca2+ sequestration differs between functionally different nerve terminals. We addressed these questions using a combination of synthetic and genetically-encoded Ca2+ indicators (GECIs) to examine cytosolic and mitochondrial Ca2+ levels in presynaptic terminals of tonic (MN13-Ib) and phasic (MNSNb/d-Is) motor neurons in Drosophila, which, as we determined, fire during fictive locomotion at ∼42 Hz and ∼8 Hz, respectively. Mitochondrial Ca2+ sequestration starts in both terminals at ∼250 nM, exhibits a similar Ca2+-uptake affinity (∼410 nM), and does not require Ca2+ release from the endoplasmic reticulum. Nonetheless, mitochondrial Ca2+ uptake in type-Is terminals is more responsive to low frequency nerve stimulation and this is due to higher cytosolic Ca2+ levels. Since type-Ib terminals have a higher mitochondrial density than Is terminals, it seemed possible that greater mitochondrial Ca2+ sequestration may be responsible for the lower cytosolic Ca2+ levels in Ib terminals. However, genetic and pharmacological manipulations of mitochondrial Ca2+ uptake did not significantly alter nerve-stimulated elevations in cytosolic Ca2+ levels in either terminal type within physiologically relevant rates of stimulation. Our findings indicate that presynaptic mitochondria have a similar affinity for Ca2+ in functionally different nerve terminals, but do not limit cytosolic Ca2+ levels within the range of motor neuron firing rates in situ. PMID:20130196

  1. Presynaptic mitochondria in functionally different motor neurons exhibit similar affinities for Ca2+ but exert little influence as Ca2+ buffers at nerve firing rates in situ.

    PubMed

    Chouhan, Amit K; Zhang, Jinhui; Zinsmaier, Konrad E; Macleod, Gregory T

    2010-02-03

    Mitochondria accumulate within nerve terminals and support synaptic function, most notably through ATP production. They can also sequester Ca(2+) during nerve stimulation, but it is unknown whether this limits presynaptic Ca(2+) levels at physiological nerve firing rates. Similarly, it is unclear whether mitochondrial Ca(2+) sequestration differs between functionally different nerve terminals. We addressed these questions using a combination of synthetic and genetically encoded Ca(2+) indicators to examine cytosolic and mitochondrial Ca(2+) levels in presynaptic terminals of tonic (MN13-Ib) and phasic (MNSNb/d-Is) motor neurons in Drosophila, which, as we determined, fire during fictive locomotion at approximately 42 Hz and approximately 8 Hz, respectively. Mitochondrial Ca(2+) sequestration starts in both terminals at approximately 250 nM, exhibits a similar Ca(2+)-uptake affinity (approximately 410 nM), and does not require Ca(2+) release from the endoplasmic reticulum. Nonetheless, mitochondrial Ca(2+) uptake in type Is terminals is more responsive to low-frequency nerve stimulation and this is due to higher cytosolic Ca(2+) levels. Since type Ib terminals have a higher mitochondrial density than Is terminals, it seemed possible that greater mitochondrial Ca(2+) sequestration may be responsible for the lower cytosolic Ca(2+) levels in Ib terminals. However, genetic and pharmacological manipulations of mitochondrial Ca(2+) uptake did not significantly alter nerve-stimulated elevations in cytosolic Ca(2+) levels in either terminal type within physiologically relevant rates of stimulation. Our findings indicate that presynaptic mitochondria have a similar affinity for Ca(2+) in functionally different nerve terminals, but do not limit cytosolic Ca(2+) levels within the range of motor neuron firing rates in situ.

  2. Visual motion integration by neurons in the middle temporal area of a New World monkey, the marmoset.

    PubMed

    Solomon, Selina S; Tailby, Chris; Gharaei, Saba; Camp, Aaron J; Bourne, James A; Solomon, Samuel G

    2011-12-01

    The middle temporal area (MT/V5) is an anatomically distinct region of primate visual cortex that is specialized for the processing of image motion. It is generally thought that some neurons in area MT are capable of signalling the motion of complex patterns, but this has only been established in the macaque monkey. We made extracellular recordings from single units in area MT of anaesthetized marmosets, a New World monkey. We show through quantitative analyses that some neurons (35 of 185; 19%) are capable of signalling pattern motion ('pattern cells'). Across several dimensions, the visual response of pattern cells in marmosets is indistinguishable from that of pattern cells in macaques. Other neurons respond to the motion of oriented contours in a pattern ('component cells') or show intermediate properties. In addition, we encountered a subset of neurons (22 of 185; 12%) insensitive to sinusoidal gratings but very responsive to plaids and other two-dimensional patterns and otherwise indistinguishable from pattern cells. We compared the response of each cell class to drifting gratings and dot fields. In pattern cells, directional selectivity was similar for gratings and dot fields; in component cells, directional selectivity was weaker for dot fields than gratings. Pattern cells were more likely to have stronger suppressive surrounds, prefer lower spatial frequencies and prefer higher speeds than component cells. We conclude that pattern motion sensitivity is a feature of some neurons in area MT of both New and Old World monkeys, suggesting that this functional property is an important stage in motion analysis and is likely to be conserved in humans.

  3. GABAergic inhibition modulates intensity sensitivity of temporally patterned pulse trains in the inferior collicular neurons in big brown bats.

    PubMed

    Luan, Rui-Hong; Wu, Fei-Jian; Jen, Philip H-S; Sun, Xin-De

    2007-12-25

    The echolocating big brown bats (Eptesicus fuscus) emit trains of frequency-modulated (FM) biosonar signals with duration, amplitude, repetition rate, and sweep structure changing systematically during interception of their prey. In the present study, the sound stimuli of temporally patterned pulse trains at three different pulse repetition rates (PRRs) were used to mimic the sounds received during search, approach, and terminal stages of echolocation. Electrophysiological method was adopted in recordings from the inferior colliculus (IC) of midbrain. By means of iontophoretic application of bicuculline, the effect of GABAergic inhibition on the intensity sensitivity of IC neurons responding to three different PRRs of 10, 30 and 90 pulses per second (pps) was examined. The rate-intensity functions (RIFs) were acquired. The dynamic range (DR) of RIFs was considered as a criterion of intensity sensitivity. Comparing the average DR of RIFs at different PRRs, we found that the intensity sensitivity of some neurons improved, but that of other neurons decayed when repetition rate of stimulus trains increased from 10 to 30 and 90 pps. During application of bicuculline, the number of impulses responding to the different pulse trains increased under all stimulating conditions, while the DR differences of RIFs at different PRRs were abolished. The results indicate that GABAergic inhibition was involved in modulating the intensity sensitivity of IC neurons responding to pulse trains at different PRRs. Before and during bicuculline application, the percentage of changes in responses was maximal in lower stimulus intensity near to the minimum threshold (MT), and decreased gradually with the increment of stimulus intensity. This observation suggests that GABAergic inhibition contributes more effectively to the intensity sensitivity of the IC neurons responding to pulse trains at lower sound level.

  4. Temporal Requirement of the Alternative Splicing Factor Sfrs1 for the Survival of Retinal Neurons

    PubMed Central

    Kanadia, Rahul N; Clark, Victoria E; Punzo, Claudio; Trimarchi, Jeffrey M; Cepko, Constance L

    2013-01-01

    Alternative splicing (AS) is the primary mechanism by which a limited number of protein coding genes can generate the proteome diversity. We have investigated the role of an alternative splicing factor (ASF), Sfrs1, an arginine/serine (SR) rich-protein family member, during retinal development. Here we report that loss of Sfrs1 function during embryonic retinal development had a profound effect such that it led to a small retina at birth. In addition, the retina underwent further degeneration in the postnatal period. Loss of Sfrs1 function resulted in the death of retinal neurons that were born during early and mid-embryonic development. Ganglion cells, cone photoreceptors, horizontal cells and amacrine cells were produced and initiated differentiation. However, these neurons subsequently underwent cell death through apoptosis. In contrast, Sfrs1 was not required for the survival of the neurons generated later, including later born amacrine cells, rod photoreceptors, bipolar cells and Müller glia. Our results highlight the requirement of Sfrs1-mediated AS for the survival of retinal neurons, with sensitivity defined by the window of time in which the neuron was generated. In all, this is the first description addressing the function of an ASF in vertebrate retinal development. PMID:18987029

  5. Attenuation of long-range temporal correlations in the amplitude dynamics of alpha and beta neuronal oscillations in patients with schizophrenia.

    PubMed

    Nikulin, Vadim V; Jönsson, Erik G; Brismar, Tom

    2012-05-15

    Although schizophrenia was previously associated with affected spatial neuronal synchronization, surprisingly little is known about the temporal dynamics of neuronal oscillations in this disease. However, given that the coordination of neuronal processes in time represents an essential aspect of practically all cognitive operations, it might be strongly affected in patients with schizophrenia. In the present study we aimed at quantifying long-range temporal correlations (LRTC) in patients (18 with schizophrenia; 3 with schizoaffective disorder) and 28 healthy control subjects matched for age and gender. Ongoing neuronal oscillations were recorded with multi-channel EEG at rest condition. LRTC in the range 5-50s were analyzed with Detrended Fluctuation Analysis. The amplitude of neuronal oscillations in alpha and beta frequency ranges did not differ between patients and control subjects. However, LRTC were strongly attenuated in patients with schizophrenia in both alpha and beta frequency ranges. Moreover, the cross-frequency correlation between LRTC belonging to alpha and beta oscillations was stronger for patients than healthy controls, indicating that similar neurophysiological processes affect neuronal dynamics in both frequency ranges. We believe that the attenuation of LRTC is most likely due to the increased variability in neuronal activity, which was previously hypothesized to underlie an excessive switching between the neuronal states in patients with schizophrenia. Attenuated LRTC might allow for more random associations between neuronal activations, which in turn might relate to the occurrence of thought disorders in schizophrenia.

  6. Temporal integration by a slowly inactivating K+ current in hippocampal neurons.

    PubMed

    Storm, J F

    1988-11-24

    A central aspect of neuronal function is how each nerve cell translated synaptic input into a sequence of action potentials that carry information along the axon, coded as spike frequency. When transduction from a graded depolarizing input to spikes is studied by injecting a depolarizing current, there is often a remarkably long delay to the first action potential, both in mammalian and molluscan neurons. Here, I report that the delayed excitation in rat hippocampal neurons is due to a slowly inactivating potassium current, ID. ID co-exists with other voltage-gated K+ currents, including a fast A current and a slow delayed rectifier current. As ID activates in the subthreshold range, and takes tens of seconds to recover from inactivation, it enables the cell to integrate separate depolarizing inputs over long times. ID also makes the encoding properties of the cell exceedingly sensitive to the prevailing membrane potential.

  7. Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children.

    PubMed

    Silva, Vernon Furtado da; Calomeni, Mauricio Rocha; Nunes, Rodolfo Alkmim Moreira; Pimentel, Carlos Elias; Martins, Gabriela Paes; Oliveira, Patrícia da Cruz Araruna; Silva, Patrícia Bagno; Silva, Alair Pedro Ribeiro de Souza E

    2016-08-01

    This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

  8. Abnormal expression of netrin-G2 in temporal lobe epilepsy neurons in humans and a rat model.

    PubMed

    Pan, Yumin; Liu, Guangwei; Fang, Min; Shen, Lan; Wang, Liang; Han, Yanbing; Shen, Dinglie; Wang, Xuefeng

    2010-08-01

    The membrane-bound axon guidance molecule netrin-g2 is preferentially expressed in the central nervous system and plays a role in synapse formation and maintenance. Using immunohistochemistry, immunofluorescence, and Western blotting, we investigated the possible correlation between netrin-g2 expression and intractable epilepsy (IE) using surgical samples from epilepsy patients. We used 35 samples of temporal neocortex from patients undergoing surgery for drug-refractory epilepsy and 15 autopsy samples from individuals who died in traffic accidents (i.e., samples of normal human brain). We also examined netrin-g2 expression in the hippocampus and adjacent cortex of rats with temporal lobe epilepsy (lithium chloride-pilocarpine model). Netrin-g2 was expressed in the membrane and cytoplasm of neurons from control specimens, and expression was higher in tissue from patients with intractable epilepsy. Western blotting of rat brain tissue showed that netrin-g2 was upregulated starting at 6h after kindling. Maximal expression was seen around 2 days, and relatively high expression was maintained until 30 days. Expression then returned to normal levels at 60 days, which was consistent with the immunohistochemical and immunofluorescence results. These data implicate netrin-g2 in the pathophysiology of epilepsy and are consistent with the hypothesis that this protein may participate in the abnormal development of synapses and in neuron migration.

  9. Optogenetic Manipulation of Activity and Temporally Controlled Cell-Specific Ablation Reveal a Role for MCH Neurons in Sleep/Wake Regulation

    PubMed Central

    Tsunematsu, Tomomi; Ueno, Takafumi; Tabuchi, Sawako; Inutsuka, Ayumu; Tanaka, Kenji F.; Hasuwa, Hidetoshi; Kilduff, Thomas S.; Terao, Akira

    2014-01-01

    Melanin-concentrating hormone (MCH) is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Recent studies have reported that MCH neurons are active during rapid eye movement (REM) sleep, but their physiological role in the regulation of sleep/wakefulness is not fully understood. To determine the physiological role of MCH neurons, newly developed transgenic mouse strains that enable manipulation of the activity and fate of MCH neurons in vivo were generated using the recently developed knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction system. The activity of these cells was controlled by optogenetics by expressing channelrhodopsin2 (E123T/T159C) or archaerhodopsin-T in MCH neurons. Acute optogenetic activation of MCH neurons at 10 Hz induced transitions from non-REM (NREM) to REM sleep and increased REM sleep time in conjunction with decreased NREM sleep. Activation of MCH neurons while mice were in NREM sleep induced REM sleep, but activation during wakefulness was ineffective. Acute optogenetic silencing of MCH neurons using archaerhodopsin-T had no effect on any vigilance states. Temporally controlled ablation of MCH neurons by cell-specific expression of diphtheria toxin A increased wakefulness and decreased NREM sleep duration without affecting REM sleep. Together, these results indicate that acute activation of MCH neurons is sufficient, but not necessary, to trigger the transition from NREM to REM sleep and that MCH neurons also play a role in the initiation and maintenance of NREM sleep. PMID:24828644

  10. Species-specificity of temporal processing in the auditory midbrain of gray treefrogs: interval-counting neurons.

    PubMed

    Rose, Gary J; Hanson, Jessica L; Leary, Christopher J; Graham, Jalina A; Alluri, Rishi K; Vasquez-Opazo, Gustavo A

    2015-05-01

    Interval-counting neurons (ICNs) respond after a threshold number of sound pulses have occurred with specific intervals; a single aberrant interval can reset the counting process. Female gray treefrogs, Hyla chrysoscelis and H. versicolor, discriminate against synthetic 'calls' possessing a single interpulse interval 2-3 three times the optimal value, suggesting that ICNs are important for call recognition. The calls of H. versicolor consist of pulses that are longer in duration, rise more slowly in amplitude and are repeated at a slower rate than those of H. chrysoscelis. Results of recordings from midbrain auditory neurons in these species include: (1) ICNs were found in both species and their temporal selectivity appeared to result from interplay between excitation and inhibition; (2) band-pass cells in H. versicolor were tuned to slower pulse rates than those in H. chrysoscelis; (3) ICNs that were selective for slow-rise pulse shape were found almost exclusively in H. versicolor, but fast-rise-selective neurons were found in both species, and (4) band-suppression ICNs in H. versicolor showed response minima at higher pulse rates than those in H. chrysoscelis. Selectivity of midbrain ICNs for pulse rise time and repetition rate thus correlate well with discriminatory abilities of these species that promote reproductive isolation.

  11. Temporal profile of apoptotic-like changes in neurons and astrocytes following controlled cortical impact injury in the rat.

    PubMed

    Newcomb, J K; Zhao, X; Pike, B R; Hayes, R L

    1999-07-01

    Apoptotic cell death has been observed in both neurodegenerative diseases and acute neurological traumas such as ischemia, spinal cord injury, and traumatic brain injury (TBI). Recent studies employing different models of TBI have described morphological and biochemical changes characteristic of apoptosis following injury. However, no study has examined the temporal profile of apoptosis following controlled cortical impact (CCI) injury in the rat. In addition, the relative frequency of apoptotic profiles in different cell types (neurons versus glia) following CCI has yet to be investigated. In the present experiments, injured cortex was subjected to DNA electrophoresis, and serial sections from the contusion area were stained with hematoxylin and eosin or Hoechst 33258 or double-labeled with TUNEL and neuronal or glial markers. The results of the present study indicate that CCI produces a substantial amount of DNA damage associated with both apoptotic-like and necrotic-like cell death phenotypes primarily at the site of cortical impact and focal contusion. DNA damage, as measured by TUNEL and DNA electrophoresis, was most apparent 1 day following injury and absent by 14 days post-TBI. However, quantitative analysis showed that the majority of TUNEL-positive cells failed to exhibit apoptotic-like morphology and were probably undergoing necrosis. In addition, apoptotic-like morphology was predominantly observed in neurons compared to astrocytes. The present study provides further evidence that apoptosis is involved in the pathology of TBI and could contribute to some of the ensuing cell death following injury.

  12. Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction

    PubMed Central

    Lincoln, Barron L.; Alabsi, Sahar H.; Frendo, Nicholas; Freund, Robert; Keller, Lani C.

    2015-01-01

    Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments. PMID:26512206

  13. Evaluation of the adaptogenic potential exerted by ginsenosides Rb1 and Rg1 against oxidative stress-mediated neurotoxicity in an in vitro neuronal model.

    PubMed

    Fernández-Moriano, Carlos; González-Burgos, Elena; Iglesias, Irene; Lozano, Rafael; Gómez-Serranillos, M Pilar

    2017-01-01

    Ginseng (Panax sp.) is a drug with multiple pharmacological actions that has been largely used in traditional medicines for the treatment of many health problems. In the therapy of neurodegenerative disorders, it has been employed due to its capacity to strengthen mental processes by enhancing cognitive performance and psychological function. Current work aimed at evaluating the adaptogenic potential of Rb1 and Rg1 against oxidative-stress mediated degeneration in a model of nervous cells. Oxidative stress and mitochondrial dysfunction were achieved by exposing SH-SY5Y cells to the mitochondrial complex I inhibitor rotenone. The cytoprotective activity of pre-treatments with ginsenosides Rb1 and Rg1 against rotenone was assessed by determining biochemical markers regarding oxidative stress (ROS scavenging, glutathione and lipid peroxidation levels, SOD activity and Nrf2 activation) and apoptosis-related alterations (mitochondrial membrane potential, calcium levels, aconitase activity and pro/antiapoptotic proteins). Their capacity to cross the blood brain barrier was also estimated. At their optimal doses, ginsenosides Rb1 and Rg1 significantly ameliorated redox status within the cells; they reduced ROS and TBARS levels and improved the glutathione system, as well as they enhanced SOD activity and Nrf2 pathway activation. They protected neuronal cells against MMP loss, calcium homeostasis disruption and aconitase inhibition. Consequently, apoptotic cell death was attenuated by the pre-treatment with ginsenosides, as evidenced by the reduction in caspase-3 and Bax, and the increase in Bcl-2 expressions; also, lower levels of cytochrome C were found in the cytosol. Poor BBB permeation was demonstrated for both ginsenosides. In conclusion, ginsenosides Rb1 and Rg1 exhibit neuroprotective potential which is achieved, at least in part, via mitochondrial protection and the plausible involvement of Nrf2 pathway activation. Our results contribute to validate the

  14. Evaluation of the adaptogenic potential exerted by ginsenosides Rb1 and Rg1 against oxidative stress-mediated neurotoxicity in an in vitro neuronal model

    PubMed Central

    Iglesias, Irene; Lozano, Rafael

    2017-01-01

    Background Ginseng (Panax sp.) is a drug with multiple pharmacological actions that has been largely used in traditional medicines for the treatment of many health problems. In the therapy of neurodegenerative disorders, it has been employed due to its capacity to strengthen mental processes by enhancing cognitive performance and psychological function. Current work aimed at evaluating the adaptogenic potential of Rb1 and Rg1 against oxidative-stress mediated degeneration in a model of nervous cells. Methods Oxidative stress and mitochondrial dysfunction were achieved by exposing SH-SY5Y cells to the mitochondrial complex I inhibitor rotenone. The cytoprotective activity of pre-treatments with ginsenosides Rb1 and Rg1 against rotenone was assessed by determining biochemical markers regarding oxidative stress (ROS scavenging, glutathione and lipid peroxidation levels, SOD activity and Nrf2 activation) and apoptosis-related alterations (mitochondrial membrane potential, calcium levels, aconitase activity and pro/antiapoptotic proteins). Their capacity to cross the blood brain barrier was also estimated. Results At their optimal doses, ginsenosides Rb1 and Rg1 significantly ameliorated redox status within the cells; they reduced ROS and TBARS levels and improved the glutathione system, as well as they enhanced SOD activity and Nrf2 pathway activation. They protected neuronal cells against MMP loss, calcium homeostasis disruption and aconitase inhibition. Consequently, apoptotic cell death was attenuated by the pre-treatment with ginsenosides, as evidenced by the reduction in caspase-3 and Bax, and the increase in Bcl-2 expressions; also, lower levels of cytochrome C were found in the cytosol. Poor BBB permeation was demonstrated for both ginsenosides. Conclusions In conclusion, ginsenosides Rb1 and Rg1 exhibit neuroprotective potential which is achieved, at least in part, via mitochondrial protection and the plausible involvement of Nrf2 pathway activation. Our

  15. Two-photon imaging of spatially extended neuronal network dynamics with high temporal resolution.

    PubMed

    Lillis, Kyle P; Eng, Alfred; White, John A; Mertz, Jerome

    2008-07-30

    We describe a simple two-photon fluorescence imaging strategy, called targeted path scanning (TPS), to monitor the dynamics of spatially extended neuronal networks with high spatiotemporal resolution. Our strategy combines the advantages of mirror-based scanning, minimized dead time, ease of implementation, and compatibility with high-resolution low-magnification objectives. To demonstrate the performance of TPS, we monitor the calcium dynamics distributed across an entire juvenile rat hippocampus (>1.5mm), at scan rates of 100 Hz, with single cell resolution and single action potential sensitivity. Our strategy for fast, efficient two-photon microscopy over spatially extended regions provides a particularly attractive solution for monitoring neuronal population activity in thick tissue, without sacrificing the signal-to-noise ratio or high spatial resolution associated with standard two-photon microscopy. Finally, we provide the code to make our technique generally available.

  16. The dynamical response properties of neocortical neurons to temporally modulated noisy inputs in vitro.

    PubMed

    Köndgen, Harold; Geisler, Caroline; Fusi, Stefano; Wang, Xiao-Jing; Lüscher, Hans-Rudolf; Giugliano, Michele

    2008-09-01

    Cortical neurons are often classified by current-frequency relationship. Such a static description is inadequate to interpret neuronal responses to time-varying stimuli. Theoretical studies suggested that single-cell dynamical response properties are necessary to interpret ensemble responses to fast input transients. Further, it was shown that input-noise linearizes and boosts the response bandwidth, and that the interplay between the barrage of noisy synaptic currents and the spike-initiation mechanisms determine the dynamical properties of the firing rate. To test these model predictions, we estimated the linear response properties of layer 5 pyramidal cells by injecting a superposition of a small-amplitude sinusoidal wave and a background noise. We characterized the evoked firing probability across many stimulation trials and a range of oscillation frequencies (1-1000 Hz), quantifying response amplitude and phase-shift while changing noise statistics. We found that neurons track unexpectedly fast transients, as their response amplitude has no attenuation up to 200 Hz. This cut-off frequency is higher than the limits set by passive membrane properties (approximately 50 Hz) and average firing rate (approximately 20 Hz) and is not affected by the rate of change of the input. Finally, above 200 Hz, the response amplitude decays as a power-law with an exponent that is independent of voltage fluctuations induced by the background noise.

  17. Effects of Category Learning on the Stimulus Selectivity of Macaque Inferior Temporal Neurons

    ERIC Educational Resources Information Center

    De Baene, Wouter; Ons, Bart; Wagemans, Johan; Vogels, Rufin

    2008-01-01

    Primates can learn to categorize complex shapes, but as yet it is unclear how this categorization learning affects the representation of shape in visual cortex. Previous studies that have examined the effect of categorization learning on shape representation in the macaque inferior temporal (IT) cortex have produced diverse and conflicting results…

  18. The Role of Short Term Synaptic Plasticity in Temporal Coding of Neuronal Networks

    ERIC Educational Resources Information Center

    Chandrasekaran, Lakshmi

    2008-01-01

    Short term synaptic plasticity is a phenomenon which is commonly found in the central nervous system. It could contribute to functions of signal processing namely, temporal integration and coincidence detection by modulating the input synaptic strength. This dissertation has two parts. First, we study the effects of short term synaptic plasticity…

  19. The Role of Short Term Synaptic Plasticity in Temporal Coding of Neuronal Networks

    ERIC Educational Resources Information Center

    Chandrasekaran, Lakshmi

    2008-01-01

    Short term synaptic plasticity is a phenomenon which is commonly found in the central nervous system. It could contribute to functions of signal processing namely, temporal integration and coincidence detection by modulating the input synaptic strength. This dissertation has two parts. First, we study the effects of short term synaptic plasticity…

  20. Flicker Adaptation of Low-Level Cortical Visual Neurons Contributes to Temporal Dilation

    ERIC Educational Resources Information Center

    Ortega, Laura; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2012-01-01

    Several seconds of adaptation to a flickered stimulus causes a subsequent brief static stimulus to appear longer in duration. Nonsensory factors, such as increased arousal and attention, have been thought to mediate this flicker-based temporal-dilation aftereffect. In this study, we provide evidence that adaptation of low-level cortical visual…

  1. Effects of Category Learning on the Stimulus Selectivity of Macaque Inferior Temporal Neurons

    ERIC Educational Resources Information Center

    De Baene, Wouter; Ons, Bart; Wagemans, Johan; Vogels, Rufin

    2008-01-01

    Primates can learn to categorize complex shapes, but as yet it is unclear how this categorization learning affects the representation of shape in visual cortex. Previous studies that have examined the effect of categorization learning on shape representation in the macaque inferior temporal (IT) cortex have produced diverse and conflicting results…

  2. Flicker Adaptation of Low-Level Cortical Visual Neurons Contributes to Temporal Dilation

    ERIC Educational Resources Information Center

    Ortega, Laura; Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Suzuki, Satoru

    2012-01-01

    Several seconds of adaptation to a flickered stimulus causes a subsequent brief static stimulus to appear longer in duration. Nonsensory factors, such as increased arousal and attention, have been thought to mediate this flicker-based temporal-dilation aftereffect. In this study, we provide evidence that adaptation of low-level cortical visual…

  3. Predicting conceptual processing capacity from spontaneous neuronal activity of the left middle temporal gyrus.

    PubMed

    Wei, Tao; Liang, Xia; He, Yong; Zang, Yufeng; Han, Zaizhu; Caramazza, Alfonso; Bi, Yanchao

    2012-01-11

    Conceptual processing is a crucial brain function for humans. Past research using neuropsychological and task-based functional brain-imaging paradigms indicates that widely distributed brain regions are related to conceptual processing. Here, we explore the potential contribution of intrinsic or spontaneous brain activity to conceptual processing by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals can account for individual differences in the conceptual processing efficiencies of healthy individuals. We acquired rs-fMRI and behavioral data on object conceptual processing tasks. We found that the regional amplitude of spontaneous low-frequency fluctuations in the blood oxygen level-dependent signal in the left (posterior) middle temporal gyrus (LMTG) was highly correlated with participants' semantic processing efficiency. Furthermore, the strength of the functional connectivity between the LMTG and a series of brain regions-the left inferior frontal gyrus, bilateral anterior temporal lobe, bilateral medial temporal lobe, posterior cingulate gyrus, and ventromedial and dorsomedial prefrontal cortices-also significantly predicted conceptual behavior. The regional amplitude of low-frequency fluctuations and functionally relevant connectivity strengths of LMTG together accounted for 74% of individual variance in object conceptual performance. This semantic network, with the LMTG as its core component, largely overlaps with the regions reported in previous conceptual/semantic task-based fMRI studies. We conclude that the intrinsic or spontaneous activity of the human brain reflects the processing efficiency of the semantic system.

  4. Parameter-sweeping techniques for temporal dynamics of neuronal systems: case study of Hindmarsh-Rose model

    PubMed Central

    2011-01-01

    Background Development of effective and plausible numerical tools is an imperative task for thorough studies of nonlinear dynamics in life science applications. Results We have developed a complementary suite of computational tools for two-parameter screening of dynamics in neuronal models. We test a ‘brute-force’ effectiveness of neuroscience plausible techniques specifically tailored for the examination of temporal characteristics, such duty cycle of bursting, interspike interval, spike number deviation in the phenomenological Hindmarsh-Rose model of a bursting neuron and compare the results obtained by calculus-based tools for evaluations of an entire spectrum of Lyapunov exponents broadly employed in studies of nonlinear systems. Conclusions We have found that the results obtained either way agree exceptionally well, and can identify and differentiate between various fine structures of complex dynamics and underlying global bifurcations in this exemplary model. Our future planes are to enhance the applicability of this computational suite for understanding of polyrhythmic bursting patterns and their functional transformations in small networks. PMID:22656867

  5. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study

    PubMed Central

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-01-01

    Abstract The spatial pattern of Na+ channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na+ channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (Vm imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  6. Temporal redistribution of inhibition over neuronal subcellular domains underlies state-dependent rhythmic change of excitability in the hippocampus.

    PubMed

    Somogyi, Peter; Katona, Linda; Klausberger, Thomas; Lasztóczi, Bálint; Viney, Tim J

    2014-02-05

    The behaviour-contingent rhythmic synchronization of neuronal activity is reported by local field potential oscillations in the theta, gamma and sharp wave-related ripple (SWR) frequency ranges. In the hippocampus, pyramidal cell assemblies representing temporal sequences are coordinated by GABAergic interneurons selectively innervating specific postsynaptic domains, and discharging phase locked to network oscillations. We compare the cellular network dynamics in the CA1 and CA3 areas recorded with or without anaesthesia. All parts of pyramidal cells, except the axon initial segment, receive GABA from multiple interneuron types, each with distinct firing dynamics. The axon initial segment is exclusively innervated by axo-axonic cells, preferentially firing after the peak of the pyramidal layer theta cycle, when pyramidal cells are least active. Axo-axonic cells are inhibited during SWRs, when many pyramidal cells fire synchronously. This dual inverse correlation demonstrates the key inhibitory role of axo-axonic cells. Parvalbumin-expressing basket cells fire phase locked to field gamma activity in both CA1 and CA3, and also strongly increase firing during SWRs, together with dendrite-innervating bistratified cells, phasing pyramidal cell discharge. Subcellular domain-specific GABAergic innervation probably developed for the coordination of multiple glutamatergic inputs on different parts of pyramidal cells through the temporally distinct activity of GABAergic interneurons, which differentially change their firing during different network states.

  7. A Computational Model Based on Multi-Regional Calcium Imaging Represents the Spatio-Temporal Dynamics in a Caenorhabditis elegans Sensory Neuron

    PubMed Central

    Kuramochi, Masahiro; Doi, Motomichi

    2017-01-01

    Due to the huge number of neuronal cells in the brain and their complex circuit formation, computer simulation of neuronal activity is indispensable to understanding whole brain dynamics. Recently, various computational models have been developed based on whole-brain calcium imaging data. However, these analyses monitor only the activity of neuronal cell bodies and treat the cells as point unit. This point-neuron model is inexpensive in computational costs, but the model is unrealistically simplistic at representing intact neural activities in the brain. Here, we describe a novel three-unit Ordinary Differential Equation (ODE) model based on the neuronal responses derived from a Caenorhabditis elegans salt-sensing neuron. We recorded calcium responses in three regions of the ASER neuron using a simple downstep of NaCl concentration. Our simple ODE model generated from a single recording can adequately reproduce and predict the temporal responses of each part of the neuron to various types of NaCl concentration changes. Our strategy which combines a simple recording data and an ODE mathematical model may be extended to realistically understand whole brain dynamics by computational simulation. PMID:28072834

  8. A Computational Model Based on Multi-Regional Calcium Imaging Represents the Spatio-Temporal Dynamics in a Caenorhabditis elegans Sensory Neuron.

    PubMed

    Kuramochi, Masahiro; Doi, Motomichi

    2017-01-01

    Due to the huge number of neuronal cells in the brain and their complex circuit formation, computer simulation of neuronal activity is indispensable to understanding whole brain dynamics. Recently, various computational models have been developed based on whole-brain calcium imaging data. However, these analyses monitor only the activity of neuronal cell bodies and treat the cells as point unit. This point-neuron model is inexpensive in computational costs, but the model is unrealistically simplistic at representing intact neural activities in the brain. Here, we describe a novel three-unit Ordinary Differential Equation (ODE) model based on the neuronal responses derived from a Caenorhabditis elegans salt-sensing neuron. We recorded calcium responses in three regions of the ASER neuron using a simple downstep of NaCl concentration. Our simple ODE model generated from a single recording can adequately reproduce and predict the temporal responses of each part of the neuron to various types of NaCl concentration changes. Our strategy which combines a simple recording data and an ODE mathematical model may be extended to realistically understand whole brain dynamics by computational simulation.

  9. Progesterone Sharpens Temporal Response Profiles of Sensory Cortical Neurons in Animals Exposed to Traumatic Brain Injury.

    PubMed

    Allitt, Benjamin J; Johnstone, Victoria P A; Richards, Katrina L; Yan, Edwin B; Rajan, Ramesh

    2017-07-01

    Traumatic brain injury (TBI) initiates a cascade of pathophysiological changes that are both complex and difficult to treat. Progesterone (P4) is a neuroprotective treatment option that has shown excellent preclinical benefits in the treatment of TBI, but these benefits have not translated well in the clinic. We have previously shown that P4 exacerbates the already hypoactive upper cortical responses in the short-term post-TBI and does not reduce upper cortical hyperactivity in the long term, and we concluded that there is no tangible benefit to sensory cortex firing strength. Here we examined the effects of P4 treatment on temporal coding resolution in the rodent sensory cortex in both the short term (4 d) and long term (8 wk) following impact-acceleration-induced TBI. We show that in the short-term postinjury, TBI has no effect on sensory cortex temporal resolution and that P4 also sharpens the response profile in all cortical layers in the uninjured brain and all layers other than layer 2 (L2) in the injured brain. In the long term, TBI broadens the response profile in all cortical layers despite firing rate hyperactivity being localized to upper cortical layers and P4 sharpens the response profile in TBI animals in all layers other than L2 and has no long-term effect in the sham brain. These results indicate that P4 has long-term effects on sensory coding that may translate to beneficial perceptual outcomes. The effects seen here, combined with previous beneficial preclinical data, emphasize that P4 is still a potential treatment option in ameliorating TBI-induced disorders.

  10. Progesterone sharpens temporal response profiles of sensory cortical neurons in animals exposed to traumatic brain injury.

    PubMed

    J Allitt, Benjamin; P A Johnstone, Victoria; L Richards, Katrina; B Yan, Edwin; Rajan, Ramesh

    2016-12-07

    Traumatic brain injury (TBI) initiates a cascade of pathophysiological changes that are both complex and difficult to treat. Progesterone (P4) is a neuroprotective treatment option that has shown excellent preclinical benefits in the treatment of TBI but these benefits have not translated well in the clinic. We have previously shown that P4 exacerbates the already hypoactive upper cortical responses in the short-term post-TBI and does not reduce upper cortical hyper-activity in the long-term, and we concluded that there is no tangible benefit to sensory cortex firing strength. Here we examined the effects of P4 treatment on temporal coding resolution in the rodent sensory cortex in both the short-term (4 days) and long-term (8 weeks) following impact acceleration-induced TBI. We show that; in the short-term post-injury TBI has no effect on sensory cortex temporal resolution and that P4 also sharpens the response profile in all cortical layers in the uninjured brain and all layers other than layer 2 in the injured brain. In the long-term TBI broadens the response profile in all cortical layers despite firing rate hyperactivity being localised to upper cortical layers and P4 sharpens the response profile in TBI animals in all layers other than L2 and has no long-term effect in the Sham brain. These results indicate that P4 has long-term effects on sensory coding that may translate to beneficial perceptual outcomes. The effects seen here, combined with previous beneficial pre-clinical data, emphasise that P4 is still a potential treatment option in ameliorating TBI induced disorders.

  11. Targeting deficiencies in mitochondrial respiratory complex I and functional uncoupling exerts anti-seizure effects in a genetic model of temporal lobe epilepsy and in a model of acute temporal lobe seizures.

    PubMed

    Simeone, Kristina A; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Timothy A

    2014-01-01

    Mitochondria actively participate in neurotransmission by providing energy (ATP) and maintaining normative concentrations of reactive oxygen species (ROS) in both presynaptic and postsynaptic elements. In human and animal epilepsies, ATP-producing respiratory rates driven by mitochondrial respiratory complex (MRC) I are reduced, antioxidant systems are attenuated and oxidative damage is increased. We report that MRCI-driven respiration and functional uncoupling (an inducible antioxidant mechanism) are reduced and levels of H2O2 are elevated in mitochondria isolated from KO mice. Experimental impairment of MRCI in WT hippocampal slices via rotenone reduces paired-pulse ratios (PPRs) at mossy fiber-CA3 synapses (resembling KO PPRs), and exacerbates seizure-like events in vitro. Daily treatment with AATP [a combination therapy composed of ascorbic acid (AA), alpha-tocopherol (T), sodium pyruvate (P) designed to synergistically target mitochondrial impairments] improved mitochondrial functions, mossy fiber PPRs, and reduced seizure burden index (SBI) scores and seizure incidence in KO mice. AATP pretreatment reduced severity of KA-induced seizures resulting in 100% protection from the severe tonic-clonic seizures in WT mice. These data suggest that restoration of bioenergetic homeostasis in the brain may represent a viable anti-seizure target for temporal lobe epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. A Temporal Association between Accumulated Petrol (Gasoline) Lead Emissions and Motor Neuron Disease in Australia.

    PubMed

    Laidlaw, Mark A S; Rowe, Dominic B; Ball, Andrew S; Mielke, Howard W

    2015-12-19

    The age standardised death rate from motor neuron disease (MND) has increased from 1.29 to 2.74 per 100,000, an increase of 112.4% between 1959 and 2013. It is clear that genetics could not have played a causal role in the increased rate of MND deaths over such a short time span. We postulate that environmental factors are responsible for this rate increase. We focus on lead additives in Australian petrol as a possible contributing environmental factor. The associations between historical petrol lead emissions and MND death trends in Australia between 1962 and 2013 were examined using linear regressions. Regression results indicate best fit correlations between a 20 year lag of petrol lead emissions and age-standardised female death rate (R² = 0.86, p = 4.88 × 10(-23)), male age standardised death rate (R² = 0.86, p = 9.4 × 10(-23)) and percent all cause death attributed to MND (R² = 0.98, p = 2.6 × 10(-44)). Legacy petrol lead emissions are associated with increased MND death trends in Australia. Further examination of the 20 year lag between exposure to petrol lead and the onset of MND is warranted.

  13. A Temporal Association between Accumulated Petrol (Gasoline) Lead Emissions and Motor Neuron Disease in Australia

    PubMed Central

    Laidlaw, Mark A. S.; Rowe, Dominic B.; Ball, Andrew S.; Mielke, Howard W.

    2015-01-01

    Background: The age standardised death rate from motor neuron disease (MND) has increased from 1.29 to 2.74 per 100,000, an increase of 112.4% between 1959 and 2013. It is clear that genetics could not have played a causal role in the increased rate of MND deaths over such a short time span. We postulate that environmental factors are responsible for this rate increase. We focus on lead additives in Australian petrol as a possible contributing environmental factor. Methods: The associations between historical petrol lead emissions and MND death trends in Australia between 1962 and 2013 were examined using linear regressions. Results: Regression results indicate best fit correlations between a 20 year lag of petrol lead emissions and age-standardised female death rate (R2 = 0.86, p = 4.88 × 10−23), male age standardised death rate (R2 = 0.86, p = 9.4 × 10−23) and percent all cause death attributed to MND (R2 = 0.98, p = 2.6 × 10−44). Conclusion: Legacy petrol lead emissions are associated with increased MND death trends in Australia. Further examination of the 20 year lag between exposure to petrol lead and the onset of MND is warranted. PMID:26703636

  14. Spatio-Temporal Dynamics of Impulse Responses to Figure Motion in Optic Flow Neurons

    PubMed Central

    Lee, Yu-Jen; Jönsson, H. Olof; Nordström, Karin

    2015-01-01

    White noise techniques have been used widely to investigate sensory systems in both vertebrates and invertebrates. White noise stimuli are powerful in their ability to rapidly generate data that help the experimenter decipher the spatio-temporal dynamics of neural and behavioral responses. One type of white noise stimuli, maximal length shift register sequences (m-sequences), have recently become particularly popular for extracting response kernels in insect motion vision. We here use such m-sequences to extract the impulse responses to figure motion in hoverfly lobula plate tangential cells (LPTCs). Figure motion is behaviorally important and many visually guided animals orient towards salient features in the surround. We show that LPTCs respond robustly to figure motion in the receptive field. The impulse response is scaled down in amplitude when the figure size is reduced, but its time course remains unaltered. However, a low contrast stimulus generates a slower response with a significantly longer time-to-peak and half-width. Impulse responses in females have a slower time-to-peak than males, but are otherwise similar. Finally we show that the shapes of the impulse response to a figure and a widefield stimulus are very similar, suggesting that the figure response could be coded by the same input as the widefield response. PMID:25955416

  15. Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices

    NASA Technical Reports Server (NTRS)

    Hof, P. R.; Nimchinsky, E. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The neurochemical characteristics of the neuronal subsets that furnish different types of corticocortical connections have been only partially determined. In recent years, several cytoskeletal proteins have emerged as reliable markers to distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In particular, previous studies using an antibody to nonphosphorylated neurofilament protein (SMI-32) have revealed a consistent degree of regional and laminar specificity in the distribution of a subpopulation of pyramidal cells in the primate cerebral cortex. The density of neurofilament protein-immunoreactive neurons was shown to vary across corticocortical pathways in macaque monkeys. In the present study, we have used the antibody SMI-32 to examine further and to quantify the distribution of a subset of corticocortically projecting neurons in a series of long ipsilateral corticocortical pathways in comparison to short corticocortical, commissural, and limbic connections. The results demonstrate that the long association pathways interconnecting the frontal, parietal, and temporal neocortex have a high representation of neurofilament protein-enriched pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic pathways are characterized by much lower numbers of such neurons (4-35%). These data suggest that different types of corticocortical connections have differential representation of highly specific neuronal subsets that share common neurochemical characteristics, thereby determining regional and laminar cortical patterns of morphological and molecular heterogeneity. These differences in neuronal neurochemical phenotype among corticocortical circuits may have considerable influence on cortical processing and may be directly related to the type of integrative function subserved by each cortical pathway. Finally, it is worth noting that neurofilament protein-immunoreactive neurons are dramatically affected in the course of

  16. Neurochemical phenotype of corticocortical connections in the macaque monkey: quantitative analysis of a subset of neurofilament protein-immunoreactive projection neurons in frontal, parietal, temporal, and cingulate cortices

    NASA Technical Reports Server (NTRS)

    Hof, P. R.; Nimchinsky, E. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The neurochemical characteristics of the neuronal subsets that furnish different types of corticocortical connections have been only partially determined. In recent years, several cytoskeletal proteins have emerged as reliable markers to distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In particular, previous studies using an antibody to nonphosphorylated neurofilament protein (SMI-32) have revealed a consistent degree of regional and laminar specificity in the distribution of a subpopulation of pyramidal cells in the primate cerebral cortex. The density of neurofilament protein-immunoreactive neurons was shown to vary across corticocortical pathways in macaque monkeys. In the present study, we have used the antibody SMI-32 to examine further and to quantify the distribution of a subset of corticocortically projecting neurons in a series of long ipsilateral corticocortical pathways in comparison to short corticocortical, commissural, and limbic connections. The results demonstrate that the long association pathways interconnecting the frontal, parietal, and temporal neocortex have a high representation of neurofilament protein-enriched pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic pathways are characterized by much lower numbers of such neurons (4-35%). These data suggest that different types of corticocortical connections have differential representation of highly specific neuronal subsets that share common neurochemical characteristics, thereby determining regional and laminar cortical patterns of morphological and molecular heterogeneity. These differences in neuronal neurochemical phenotype among corticocortical circuits may have considerable influence on cortical processing and may be directly related to the type of integrative function subserved by each cortical pathway. Finally, it is worth noting that neurofilament protein-immunoreactive neurons are dramatically affected in the course of

  17. Enhancement of temporal coherence via time-periodic coupling strength in a scale-free network of stochastic Hodgkin-Huxley neurons

    NASA Astrophysics Data System (ADS)

    Yilmaz, Ergin; Baysal, Veli; Ozer, Mahmut

    2015-08-01

    We investigate the effects of time-periodic coupling strength on the temporal coherence or firing regularity of a scale-free network consisting of stochastic Hodgkin-Huxley (H-H) neurons. The temporal coherence exhibits a resonance-like behavior depending on the cell size or the channel noise intensity. The best temporal coherence requires an optimal channel noise intensity, and this coherence can be significantly increased by time-periodic coupling strength when its frequency matches the integer multiples of the intrinsic subthreshold oscillation frequency of H-H neuron. Particularly, we find the multiple-coherence resonance depending on frequency of time-periodic coupling strength at the optimal noise intensity. We also obtain a resonance-like dependence of temporal coherence on the amplitude of time-periodic coupling strength. Additionally, we investigate the effects of average degree on the temporal coherence and find that the temporal coherence exhibits a resonance-like behavior with respect to the network average degree, indicating that the best regularity requires an optimal average degree.

  18. Exercise intensity influences the temporal profile of growth factors involved in neuronal plasticity following focal ischemia.

    PubMed

    Ploughman, Michelle; Granter-Button, Shirley; Chernenko, Garry; Attwood, Zachary; Tucker, Budd A; Mearow, Karen M; Corbett, Dale

    2007-05-30

    Exercise increases brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response-element binding protein (pCREB), insulin-like growth factor (IGF-I) and synapsin-I, each of which has been implicated in neuroplastic processes underlying recovery from ischemia. In this study we examined the temporal profile (0, 30, 60 and 120 min following exercise) of these proteins in the hippocampus and sensorimotor cortex following both motorized (60 min) and voluntary (12 h) running, 2 weeks after focal ischemia. Our goal was to identify the optimal training paradigms (intensity, duration and frequency) needed to integrate endurance exercise in stroke rehabilitation. Therefore we utilized telemetry to measure changes in heart rate with both exercise methods. Our findings show that although the more intense, motorized running exercise induced a rapid increase in BDNF, the elevation was more short-lived than with voluntary running. Motorized running was also associated with higher levels of synapsin-I in several brain regions but simultaneously, a more pronounced increase in the stress hormone, corticosterone. Furthermore, both forms of exercise resulted in decreased phosphorylation of CREB and downregulation of synapsin-I in hippocampus beginning 30 to 60 min after the exercise bout. This phenomenon was more robust after motorized running, the method that generated higher heart rate and serum corticosterone levels. This immediate stress response is likely specific to acute exercise and may diminish with repeated exercise exposure. The present data illustrate a complex interaction between different forms of exercise and proteins implicated in neuroplasticity. For clinical application, frequent lower intensity exercise episodes (as in voluntary running wheels), which may be safer to provide to patients with stroke, has a delayed but sustained effect on BDNF that may support brain remodeling after stroke.

  19. Slow temporal filtering may largely explain the transformation of stick insect (Carausius morosus) extensor motor neuron activity into muscle movement.

    PubMed

    Hooper, Scott L; Guschlbauer, Christoph; von Uckermann, Géraldine; Büschges, Ansgar

    2007-09-01

    Understanding how nervous systems generate behavior requires understanding how muscles transform neural input into movement. The stick insect extensor tibiae muscle is an excellent system in which to study this issue because extensor motor neuron activity is highly variable during single leg walking and extensor muscles driven with this activity produce highly variable movements. We showed earlier that spike number, not frequency, codes for extensor amplitude during contraction rises, which implies the muscle acts as a slow filter on the time scale of burst interspike intervals (5-10 ms). We examine here muscle response to spiking variation over entire bursts, a time scale of hundreds of milliseconds, and directly measure muscle time constants. Muscle time constants differ during contraction and relaxation, and contraction time constants, although variable, are always extremely slow (200-700 ms). Models using these data show that extremely slow temporal filtering alone can explain much of the observed transform properties. This work also revealed an unexpected (to us) ability of slow filtering to transform steadily declining inputs into constant amplitude outputs. Examination of the effects of time constant variability on model output showed that variation within an SD primarily altered output amplitude, but variation across the entire range also altered contraction shape. These substantial changes suggest that understanding the basis of this variation is central to predicting extensor activity and that the animal could theoretically vary muscle time constant to match extensor response to changing behavioral need.

  20. Adult newborn neurons are involved in learning acquisition and long-term memory formation: the distinct demands on temporal neurogenesis of different cognitive tasks.

    PubMed

    Suárez-Pereira, Irene; Canals, Santiago; Carrión, Angel M

    2015-01-01

    There is evidence that adult hippocampal neurogenesis influences hippocampal function, although the role these neurons fulfill in learning and consolidation processes remains unclear. Using a novel fast X-ray ablation protocol to deplete neurogenic cells, we demonstrate that immature adult hippocampal neurons are required for hippocampal learning and long-term memory formation. Moreover, we found that long-term memory formation in the object recognition and passive avoidance tests, two paradigms that involve circuits with distinct emotional components, had different temporal demands on hippocampal neurogenesis. These results reveal new and unexpected aspects of neurogenesis in cognitive processes. © 2014 Wiley Periodicals, Inc.

  1. Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

    2014-01-01

    Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

  2. Chronic Exertional Compartment Syndrome

    MedlinePlus

    ... through the pain; that can lead to permanent muscle or nerve damage. Sometimes chronic exertional compartment syndrome is mistaken for shin splints, a more common cause of leg pain in young people who do a lot of vigorous weight- ...

  3. Morphology and kainate-receptor immunoreactivity of identified neurons within the entorhinal cortex projecting to superior temporal sulcus in the cynomolgus monkey

    NASA Technical Reports Server (NTRS)

    Good, P. F.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de No (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.

  4. Ecdysterone protects gerbil brain from temporal global cerebral ischemia/reperfusion injury via preventing neuron apoptosis and deactivating astrocytes and microglia cells.

    PubMed

    Wang, Wei; Wang, Tao; Feng, Wan-Yu; Wang, Zhan-You; Cheng, Mao-Sheng; Wang, Yun-Jie

    2014-01-01

    Ecdysterone (EDS), a common derivative of ecdysteroid, has shown its effects on alleviating cognitive impairment and improving the cognition and memory. However, the mechanisms remain unknown. Using temporal global forebrain ischemia and reperfusion-induced brain injury as a model system, we investigated the roles of EDS in improving cognitive impairment in gerbil. Our results demonstrated that intraperitoneal injection of EDS obviously increased the number of surviving neuron cells by Nissl and neuronal nuclei (NeuN) staining. Indeed, the protecting effects of EDS are because of its ability to prevent the apoptosis of neuron cells as evidenced by TUNEL staining and caspase-3 deactivation in the brain of temporal global forebrain ischemia/reperfusion-treated gerbil. Moreover, EDS administration suppressed the ischemia stimulated activity of astrocytes and microglia cells by inhibiting the production of tumor necrosis alpha (TNF-α) in the brain of gerbil. More importantly, these actions of neurons and astrocytes/microglia cells in response to EDS treatment played pivotal roles in ameliorating the cognitive impairment in the ischemia/reperfusion-injured gerbil. In view of these observations, we not only decipher the mechanisms of EDS in reducing the syndrome of ischemia, but also provide novel perspectives to combat ischemic stroke.

  5. Organization and trade-off of spectro-temporal tuning properties of duration-tuned neurons in the mammalian inferior colliculus

    PubMed Central

    Morrison, James A.; Farzan, Faranak; Fremouw, Thane; Sayegh, Riziq; Covey, Ellen

    2014-01-01

    Neurons throughout the mammalian central auditory pathway respond selectively to stimulus frequency and amplitude, and some are also selective for stimulus duration. First found in the auditory midbrain or inferior colliculus (IC), these duration-tuned neurons (DTNs) provide a potential neural mechanism for encoding temporal features of sound. In this study, we investigated how having an additional neural response filter, one selective to the duration of an auditory stimulus, influences frequency tuning and neural organization by recording single-unit responses and measuring the dorsal-ventral position and spectral-temporal tuning properties of auditory DTNs from the IC of the awake big brown bat (Eptesicus fuscus). Like other IC neurons, DTNs were tonotopically organized and had either V-shaped, U-shaped, or O-shaped frequency tuning curves (excitatory frequency response areas). We hypothesized there would be an interaction between frequency and duration tuning in DTNs, as electrical engineering theory for resonant filters dictates a trade-off in spectral-temporal resolution: sharp tuning in the frequency domain results in poorer resolution in the time domain and vice versa. While the IC is a more complex signal analyzer than an electrical filter, a similar operational trade-off could exist in the responses of DTNs. Our data revealed two patterns of spectro-temporal sensitivity and spatial organization within the IC: DTNs with sharp frequency tuning and broad duration tuning were located in the dorsal IC, whereas cells with wide spectral tuning and narrow temporal tuning were found in the ventral IC. PMID:24572091

  6. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward

    PubMed Central

    Calipari, Erin S.; Bagot, Rosemary C.; Purushothaman, Immanuel; Davidson, Thomas J.; Yorgason, Jordan T.; Peña, Catherine J.; Walker, Deena M.; Pirpinias, Stephen T.; Guise, Kevin G.; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J.

    2016-01-01

    The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context–reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse. PMID:26831103

  7. A million-plus neuron model of the hippocampal dentate gyrus: Dependency of spatio-temporal network dynamics on topography.

    PubMed

    Hendrickson, Phillip J; Yu, Gene J; Song, Dong; Berger, Theodore W

    2015-01-01

    This paper describes a million-plus granule cell compartmental model of the rat hippocampal dentate gyrus, including excitatory, perforant path input from the entorhinal cortex, and feedforward and feedback inhibitory input from dentate interneurons. The model includes experimentally determined morphological and biophysical properties of granule cells, together with glutamatergic AMPA-like EPSP and GABAergic GABAA-like IPSP synaptic excitatory and inhibitory inputs, respectively. Each granule cell was composed of approximately 200 compartments having passive and active conductances distributed throughout the somatic and dendritic regions. Modeling excitatory input from the entorhinal cortex was guided by axonal transport studies documenting the topographical organization of projections from subregions of the medial and lateral entorhinal cortex, plus other important details of the distribution of glutamatergic inputs to the dentate gyrus. Results showed that when medial and lateral entorhinal cortical neurons maintained Poisson random firing, dentate granule cells expressed, throughout the million-cell network, a robust, non-random pattern of spiking best described as spatiotemporal "clustering". To identify the network property or properties responsible for generating such firing "clusters", we progressively eliminated from the model key mechanisms such as feedforward and feedback inhibition, intrinsic membrane properties underlying rhythmic burst firing, and/or topographical organization of entorhinal afferents. Findings conclusively identified topographical organization of inputs as the key element responsible for generating a spatio-temporal distribution of clustered firing. These results uncover a functional organization of perforant path afferents to the dentate gyrus not previously recognized: topography-dependent clusters of granule cell activity as "functional units" that organize the processing of entorhinal signals.

  8. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward.

    PubMed

    Calipari, Erin S; Bagot, Rosemary C; Purushothaman, Immanuel; Davidson, Thomas J; Yorgason, Jordan T; Peña, Catherine J; Walker, Deena M; Pirpinias, Stephen T; Guise, Kevin G; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J

    2016-03-08

    The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context-reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse.

  9. Multifaceted role of nitric oxide in an in vitro mouse neuronal injury model: transcriptomic profiling defines the temporal recruitment of death signalling cascades

    PubMed Central

    Peng, Zhao Feng; Chen, Minghui Jessica; Manikandan, Jayapal; Melendez, Alirio J; Shui, Guanghou; Russo-Marie, Françoise; Whiteman, Matthew; Beart, Philip M; Moore, Philip K; Cheung, Nam Sang

    2012-01-01

    Abstract Nitric oxide is implicated in the pathogenesis of various neuropathologies characterized by oxidative stress. Although nitric oxide has been reported to be involved in the exacerbation of oxidative stress observed in several neuropathologies, existent data fail to provide a holistic description of how nitrergic pathobiology elicits neuronal injury. Here we provide a comprehensive description of mechanisms contributing to nitric oxide induced neuronal injury by global transcriptomic profiling. Microarray analyses were undertaken on RNA from murine primary cortical neurons treated with the nitric oxide generator DETA-NONOate (NOC-18, 0.5 mM) for 8–24 hrs. Biological pathway analysis focused upon 3672 gene probes which demonstrated at least a ±1.5-fold expression in a minimum of one out of three time-points and passed statistical analysis (one-way anova, P < 0.05). Numerous enriched processes potentially determining nitric oxide mediated neuronal injury were identified from the transcriptomic profile: cell death, developmental growth and survival, cell cycle, calcium ion homeostasis, endoplasmic reticulum stress, oxidative stress, mitochondrial homeostasis, ubiquitin-mediated proteolysis, and GSH and nitric oxide metabolism. Our detailed time-course study of nitric oxide induced neuronal injury allowed us to provide the first time a holistic description of the temporal sequence of cellular events contributing to nitrergic injury. These data form a foundation for the development of screening platforms and define targets for intervention in nitric oxide neuropathologies where nitric oxide mediated injury is causative. PMID:21352476

  10. Emphasis of spatial cues in the temporal fine structure during the rising segments of amplitude-modulated sounds II: single-neuron recordings

    PubMed Central

    Marquardt, Torsten; Stange, Annette; Pecka, Michael; Grothe, Benedikt; McAlpine, David

    2014-01-01

    Recently, with the use of an amplitude-modulated binaural beat (AMBB), in which sound amplitude and interaural-phase difference (IPD) were modulated with a fixed mutual relationship (Dietz et al. 2013b), we demonstrated that the human auditory system uses interaural timing differences in the temporal fine structure of modulated sounds only during the rising portion of each modulation cycle. However, the degree to which peripheral or central mechanisms contribute to the observed strong dominance of the rising slope remains to be determined. Here, by recording responses of single neurons in the medial superior olive (MSO) of anesthetized gerbils and in the inferior colliculus (IC) of anesthetized guinea pigs to AMBBs, we report a correlation between the position within the amplitude-modulation (AM) cycle generating the maximum response rate and the position at which the instantaneous IPD dominates the total neural response. The IPD during the rising segment dominates the total response in 78% of MSO neurons and 69% of IC neurons, with responses of the remaining neurons predominantly coding the IPD around the modulation maximum. The observed diversity of dominance regions within the AM cycle, especially in the IC, and its comparison with the human behavioral data suggest that only the subpopulation of neurons with rising slope dominance codes the sound-source location in complex listening conditions. A comparison of two models to account for the data suggests that emphasis on IPDs during the rising slope of the AM cycle depends on adaptation processes occurring before binaural interaction. PMID:24554782

  11. Stereological analysis of GluR2-immunoreactive hilar neurons in the pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Jiao, Yiqun; Nadler, J. Victor

    2007-01-01

    Mossy fiber sprouting and the genesis of ectopic granule cells contribute to reverberating excitation in the dentate gyrus of epileptic brain. This study determined whether the extent of sprouting after status epilepticus in rats correlates with the seizure-induced degeneration of GluR2-immunoreactive (GluR2+) hilar neurons (presumptive mossy cells) and also quantitated granule cell-like GluR2-immunoreactive hilar neurons. Stereological cell counting indicated that GluR2+ neurons account for 57% of the total hilar neuron population. Prolonged pilocarpine-induced status epilepticus killed 95% of these cells. A smaller percentage of GluR2+ neurons (74%) was killed when status epilepticus was interrupted after 1-3.5 h with a single injection of phenobarbital, and the number of residual GluR2+ neurons varied among animals by a factor of 6.2. GluR2+ neurons were not necessarily more vulnerable than other hilar neurons. In rats administered phenobarbital, the extent of recurrent mossy fiber growth varied inversely and linearly with the number of GluR2+ hilar neurons that remained intact (P = 0.0001). Thus the loss of each GluR2+ neuron was associated with roughly the same amount of sprouting. These findings support the hypothesis that mossy fiber sprouting is driven largely by the degeneration of and/or loss of innervation from mossy cells. Granule cell-like GluR2-immunoreactive neurons were rarely encountered in the hilus of control rats, but increased 6- to 140-fold after status epilepticus. Their number did not correlate with the extent of hilar cell death or mossy fiber sprouting in the same animal. The morphology, number, and distribution of these neurons suggested that they were hilar ectopic granule cells. PMID:17475251

  12. The chemosensory basis for behavioral divergence involved in sympatric host shifts II: olfactory receptor neuron sensitivity and temporal firing pattern to individual key host volatiles.

    PubMed

    Olsson, Shannon B; Linn, Charles E; Roelofs, Wendell L

    2006-03-01

    The Rhagoletis species complex has been a key player in the sympatric speciation debate for much of the last 50 years. Studies indicate that differences in olfactory preference for host fruit volatiles could be important in reproductively isolating flies infesting each type of fruit via premating barriers to gene flow. Single sensillum electrophysiology was used to compare the response characteristics of olfactory receptor neurons from apple, hawthorn, and flowering dogwood-origin populations of R. pomonella, as well as from the blueberry maggot, R. mendax (an outgroup). Eleven volatiles were selected as stimuli from behavioral/electroantennographic studies of the three R. pomonella host populations. Previously, we reported that differences in preference for host fruit volatile blends are not a function of alterations in the general class of receptor neurons tuned to key host volatiles. In the present study, population comparisons involving dose-response trials with the key volatiles revealed significant variability in olfactory receptor neuron sensitivity and temporal firing pattern both within and among Rhagoletis populations. It is concluded that such variability in peripheral sensitivity and temporal firing pattern could influence host preference and contribute to host fidelity and sympatric host shifts in the Rhagoletis complex.

  13. Exertional Rhabdomyolysis after Spinning

    PubMed Central

    Jeong, Youjin; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

    2016-01-01

    Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24–48 hours after attending a spinning class at a local gymnasium. Paired with key laboratory findings, her symptoms were suggestive of rhabdomyolysis. She required hospital admission to sustain renal function through fluid resuscitation therapy and fluid balance monitoring. Because exertional rhabdomyolysis may occur in any unfit but otherwise healthy individual who indulges in stationary cycling, the potential health risks of this activity must be considered. PMID:27900075

  14. Exertional Rhabdomyolysis after Spinning.

    PubMed

    Jeong, Youjin; Kweon, Hyuk-Jung; Oh, Eun-Jung; Ahn, Ah-Leum; Choi, Jae-Kyung; Cho, Dong-Yung

    2016-11-01

    Any strenuous muscular exercise may trigger rhabdomyolysis. We report an episode of clinically manifested exertional rhabdomyolysis due to stationary cycling, commonly known as spinning. Reports of spinning-related rhabdomyolysis are rare in the English literature, and the current case appears to be the first such case reported in South Korea. A previously healthy 21-year-old Asian woman presented with severe thigh pain and reddish-brown urinary discoloration 24-48 hours after attending a spinning class at a local gymnasium. Paired with key laboratory findings, her symptoms were suggestive of rhabdomyolysis. She required hospital admission to sustain renal function through fluid resuscitation therapy and fluid balance monitoring. Because exertional rhabdomyolysis may occur in any unfit but otherwise healthy individual who indulges in stationary cycling, the potential health risks of this activity must be considered.

  15. RELN-expressing Neuron Density in Layer I of the Superior Temporal Lobe is Similar in Human Brains with Autism and in Age-Matched Controls

    PubMed Central

    Camacho, Jasmin; Ejaz, Ehsan; Ariza, Jeanelle; Noctor, Stephen C.; Martínez-Cerdeño, Verónica

    2015-01-01

    Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in layer I, and by pyramidal cells and GABAergic interneurons in deeper cortical layers. It is widely believed that decreased RELN in layer I of the cerebral cortex of subjects with autism may result from a decrease in the density of RELN expressing neurons in layer I; however, this hypothesis has not been tested. We examined RELN expression in layer I of the adult human cortex and found that 70% of cells express RELN in both control and autistic subjects. We quantified the density of neurons in layer I of the superior temporal cortex of subjects with autism and age-matched control subjects. Our data show that there is no change in the density of neurons in layer I of the cortex of subjects with autism, and therefore suggest that reduced RELN expression in the cerebral cortex of subjects with autism is not a consequence of decreased numbers of RELN-expressing neurons in layer I. Instead reduced RELN may result from abnormal RELN processing, or a decrease in the number of other RELN-expressing neuronal cell types. PMID:25067827

  16. RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls.

    PubMed

    Camacho, Jasmin; Ejaz, Ehsan; Ariza, Jeanelle; Noctor, Stephen C; Martínez-Cerdeño, Verónica

    2014-09-05

    Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in layer I, and by pyramidal cells and GABAergic interneurons in deeper cortical layers. It is widely believed that decreased RELN in layer I of the cerebral cortex of subjects with autism may result from a decrease in the density of RELN expressing neurons in layer I; however, this hypothesis has not been tested. We examined RELN expression in layer I of the adult human cortex and found that 70% of cells express RELN in both control and autistic subjects. We quantified the density of neurons in layer I of the superior temporal cortex of subjects with autism and age-matched control subjects. Our data show that there is no change in the density of neurons in layer I of the cortex of subjects with autism, and therefore suggest that reduced RELN expression in the cerebral cortex of subjects with autism is not a consequence of decreased numbers of RELN-expressing neurons in layer I. Instead reduced RELN may result from abnormal RELN processing, or a decrease in the number of other RELN-expressing neuronal cell types. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease.

    PubMed

    Armstrong, Richard A; Gearing, Marla; Bigio, Eileen H; Cruz-Sanchez, Felix F; Duyckaerts, Charles; Mackenzie, Ian R A; Perry, Robert H; Skullerud, Kari; Yokoo, Hedeaki; Cairns, Nigel J

    2011-02-01

    Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of familial amyotrophic lateral sclerosis with FUS mutation, NIFID, basophilic inclusion body disease, and atypical FTLD with ubiquitin-immunoreactive inclusions (aFTLD-U). To further characterize FUS proteinopathy in NIFID, and to determine whether the pathology revealed by FUS immunohistochemistry (IHC) is more extensive than α-internexin, we have undertaken a quantitative assessment of ten clinically and neuropathologically well-characterized cases using FUS IHC. The densities of NCI were greatest in the dentate gyrus (DG) and in sectors CA1/2 of the hippocampus. Anti-FUS antibodies also labeled glial inclusions (GI), neuronal intranuclear inclusions (NII), and dystrophic neurites (DN). Vacuolation was extensive across upper and lower cortical layers. Significantly greater densities of abnormally enlarged neurons and glial cell nuclei were present in the lower compared with the upper cortical laminae. FUS IHC revealed significantly greater numbers of NCI in all brain regions especially the DG. Our data suggest: (1) significant densities of FUS-immunoreactive NCI in NIFID especially in the DG and CA1/2; (2) infrequent FUS-immunoreactive GI, NII, and DN; (3) widely distributed vacuolation across the cortex, and (4) significantly more NCI revealed by FUS than α-internexin IHC.

  18. Functional profile of the giant metacerebral neuron of Helix aspersa: temporal and spatial dynamics of electrical activity in situ

    PubMed Central

    Antic, Srdjan; Wuskell, Joseph P; Loew, Leslie; Zecevic, Dejan

    2000-01-01

    Understanding the biophysical properties of single neurons and how they process information is fundamental to understanding how the brain works. However, action potential initiation and the preceding integration of the synaptic signals in neuronal processes of individual cells are complex and difficult to understand in the absence of detailed, spatially resolved measurements. Multi-site optical recording with voltage-sensitive dyes from individual neurons in situ was used to provide these kinds of measurements. We analysed in detail the pattern of initiation and propagation of spikes evoked synaptically in an identified snail (Helix aspersa) neuron in situ. Two main spike trigger zones were identified. The trigger zones were activated selectively by different sets of synaptic inputs which also produced different spike propagation patterns. Synaptically evoked action potentials did not always invade all parts of the neuron. The conduction of the axonal spike was regularly blocked at particular locations on neuronal processes. The propagating spikes in some axonal branches consistently reversed direction at certain branch points, a phenomenon known as reflection. These experimental results, when linked to a computer model, could allow a new level of analysis of the electrical structure of single neurons. PMID:10944170

  19. Synaptic plasticity in neuronal network models can explain patterns of bursting activity seen in temporal lobe epileptic seizures.

    PubMed

    Kudela, Pawel; Franszczuk, Piotr J; Bergey, Gregory K

    2004-01-01

    High-resolution time-frequency analyses of ictal EEG allow for identification and characterization of ictal patterns. These patterns reflect alterations in the brain network synchrony. It is not clear why seizures undergo these dynamical changes and what mechanisms contribute to or cause these changes. In this work we use neural modeling studies to address these issues. We investigate the role of synaptic plasticity and nonsynaptic neuronal plasticity (firing frequency adaptation) in regulating pattern of neuronal network synchrony. We show that nonsynaptic neuronal plasticity (i.e. calcium dependent afterhyperpolarization in neurons) can regulate the frequency of the dominant rhythm in EEG while synaptic potentiation may be responsible for irregular bursting prior to seizure termination.

  20. Chronic Exertional Compartment Syndrome.

    PubMed

    Braver, Richard T

    2016-04-01

    Increased tissue pressure within a fascial compartment may be the result from any increase in volume within its contents, or any decrease in size of the fascial covering or its distensibility. This may lead to symptoms of leg tightness, pain or numbness brought about by exercise. There are multiple differential diagnoses of exercise induced leg pain and the proper diagnoses of chronic exertional compartment syndrome (CECS) is made by a careful history and by exclusion of other maladies and confirmed by compartment syndrome testing as detailed in this text. Surgical fasciotomies for the anterior, lateral, superficial and deep posterior compartments are described in detail along with ancillary procedures for chronic shin splints that should allow the athlete to return to competitive activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Frequent globular neuronal cytoplasmic inclusions in the medial temporal region as a possible characteristic feature in multiple system atrophy with dementia.

    PubMed

    Homma, Taku; Mochizuki, Yoko; Komori, Takashi; Isozaki, Eiji

    2016-10-01

    Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha-synuclein-related multisystem neurodegeneration, so-called alpha-synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy-proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA-D). Compared with MSA cases without dementia, MSA-D cases had frequent globular NCIs (G-NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA-D cases could be divided into two types; MSA-D with distinct fronto-temporal lobar degeneration (FTLD type) and without distinct fronto-temporal lobar degeneration (non-FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G-NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA-D, even when a case with MSA-D reveals no significant cerebral atrophy.

  2. Early mechanisms of pathobiology are revealed by transcriptional temporal dynamics in hippocampal CA1 neurons of prion infected mice.

    PubMed

    Majer, Anna; Medina, Sarah J; Niu, Yulian; Abrenica, Bernard; Manguiat, Kathy J; Frost, Kathy L; Philipson, Clark S; Sorensen, Debra L; Booth, Stephanie A

    2012-01-01

    Prion diseases typically have long pre-clinical incubation periods during which time the infectious prion particle and infectivity steadily propagate in the brain. Abnormal neuritic sprouting and synaptic deficits are apparent during pre-clinical disease, however, gross neuronal loss is not detected until the onset of the clinical phase. The molecular events that accompany early neuronal damage and ultimately conclude with neuronal death remain obscure. In this study, we used laser capture microdissection to isolate hippocampal CA1 neurons and determined their pre-clinical transcriptional response during infection. We found that gene expression within these neurons is dynamic and characterized by distinct phases of activity. We found that a major cluster of genes is altered during pre-clinical disease after which expression either returns to basal levels, or alternatively undergoes a direct reversal during clinical disease. Strikingly, we show that this cluster contains a signature highly reminiscent of synaptic N-methyl-D-aspartic acid (NMDA) receptor signaling and the activation of neuroprotective pathways. Additionally, genes involved in neuronal projection and dendrite development were also altered throughout the disease, culminating in a general decline of gene expression for synaptic proteins. Similarly, deregulated miRNAs such as miR-132-3p, miR-124a-3p, miR-16-5p, miR-26a-5p, miR-29a-3p and miR-140-5p follow concomitant patterns of expression. This is the first in depth genomic study describing the pre-clinical response of hippocampal neurons to early prion replication. Our findings suggest that prion replication results in the persistent stimulation of a programmed response that is mediated, at least in part, by synaptic NMDA receptor activity that initially promotes cell survival and neurite remodelling. However, this response is terminated prior to the onset of clinical symptoms in the infected hippocampus, seemingly pointing to a critical juncture in

  3. Information Accumulation over Time in Monkey Inferior Temporal Cortex Neurons Explains Pattern Recognition Reaction Time under Visual Noise.

    PubMed

    Kuboki, Ryosuke; Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Richmond, Barry J; Shidara, Munetaka

    2016-01-01

    We recognize objects even when they are partially degraded by visual noise. We studied the relation between the amount of visual noise (5, 10, 15, 20, or 25%) degrading 8 black-and-white stimuli and stimulus identification in 2 monkeys performing a sequential delayed match-to-sample task. We measured the accuracy and speed with which matching stimuli were identified. The performance decreased slightly (errors increased) as the amount of visual noise increased for both monkeys. The performance remained above 80% correct, even with 25% noise. However, the reaction times markedly increased as the noise increased, indicating that the monkeys took progressively longer to decide what the correct response would be as the amount of visual noise increased, showing that the monkeys trade time to maintain accuracy. Thus, as time unfolds the monkeys act as if they are accumulating the information and/or testing hypotheses about whether the test stimulus is likely to be a match for the sample being held in short-term memory. We recorded responses from 13 single neurons in area TE of the 2 monkeys. We found that stimulus-selective information in the neuronal responses began accumulating when the match stimulus appeared. We found that the greater the amount of noise obscuring the test stimulus, the more slowly stimulus-related information by the 13 neurons accumulated. The noise induced slowing was about the same for both behavior and information. These data are consistent with the hypothesis that area TE neuron population carries information about stimulus identity that accumulates over time in such a manner that it progressively overcomes the signal degradation imposed by adding visual noise.

  4. Information Accumulation over Time in Monkey Inferior Temporal Cortex Neurons Explains Pattern Recognition Reaction Time under Visual Noise

    PubMed Central

    Kuboki, Ryosuke; Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Richmond, Barry J.; Shidara, Munetaka

    2017-01-01

    We recognize objects even when they are partially degraded by visual noise. We studied the relation between the amount of visual noise (5, 10, 15, 20, or 25%) degrading 8 black-and-white stimuli and stimulus identification in 2 monkeys performing a sequential delayed match-to-sample task. We measured the accuracy and speed with which matching stimuli were identified. The performance decreased slightly (errors increased) as the amount of visual noise increased for both monkeys. The performance remained above 80% correct, even with 25% noise. However, the reaction times markedly increased as the noise increased, indicating that the monkeys took progressively longer to decide what the correct response would be as the amount of visual noise increased, showing that the monkeys trade time to maintain accuracy. Thus, as time unfolds the monkeys act as if they are accumulating the information and/or testing hypotheses about whether the test stimulus is likely to be a match for the sample being held in short-term memory. We recorded responses from 13 single neurons in area TE of the 2 monkeys. We found that stimulus-selective information in the neuronal responses began accumulating when the match stimulus appeared. We found that the greater the amount of noise obscuring the test stimulus, the more slowly stimulus-related information by the 13 neurons accumulated. The noise induced slowing was about the same for both behavior and information. These data are consistent with the hypothesis that area TE neuron population carries information about stimulus identity that accumulates over time in such a manner that it progressively overcomes the signal degradation imposed by adding visual noise. PMID:28127279

  5. Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy

    PubMed Central

    Do Val-da Silva, Raquel A.; Peixoto-Santos, Jose E.; Kandratavicius, Ludmyla; De Ross, Jana B.; Esteves, Ingrid; De Martinis, Bruno S.; Alves, Marcela N. R.; Scandiuzzi, Renata C.; Hallak, Jaime E. C.; Zuardi, Antonio W.; Crippa, Jose A.; Leite, Joao P.

    2017-01-01

    The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5–4 Hz) and theta (4–10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders. PMID:28367124

  6. Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy.

    PubMed

    Do Val-da Silva, Raquel A; Peixoto-Santos, Jose E; Kandratavicius, Ludmyla; De Ross, Jana B; Esteves, Ingrid; De Martinis, Bruno S; Alves, Marcela N R; Scandiuzzi, Renata C; Hallak, Jaime E C; Zuardi, Antonio W; Crippa, Jose A; Leite, Joao P

    2017-01-01

    The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5-4 Hz) and theta (4-10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders.

  7. A novel function for Wnt signaling modulating neuronal firing activity and the temporal structure of spontaneous oscillation in the entorhinal-hippocampal circuit.

    PubMed

    Oliva, Carolina A; Inestrosa, Nibaldo C

    2015-07-01

    circuital activity has dominated. In summary, the amount of Wnt that is being released can exert a fine tuning of the physiological output, modulating firing activity, improving reliability of communication between neurons, and maintaining a continuous self-regulatory cycle of synaptic structure-function that can be present during all postnatal life. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Integration of synchronous synaptic input in CA1 pyramidal neuron depends on spatial and temporal distributions of the input.

    PubMed

    Tigerholm, Jenny; Migliore, Michele; Fransén, Erik

    2013-01-01

    Highly synchronized neural firing has been discussed in relation to learning and memory, for instance sharp-wave activity in hippocampus. We were interested to study how a postsynaptic CA1 pyramidal neuron would integrate input of different levels of synchronicity. In previous work using computational modeling we studied how the integration depends on dendritic conductances. We found that the transient A-type potassium channel K(A) was able to selectively suppress input of high synchronicity. In recent years, compartmentalization of dendritic integration has been shown. We were therefore interested to study the influence of localization and pattern of synaptic input over the dendritic tree of the CA1 pyramidal neuron. We find that the selective suppression increases when synaptic inputs are placed on oblique dendrites further out from the soma. The suppression also increases along the radial axis from the apical trunk out to the end of oblique dendrites. We also find that the K(A) channel suppresses the occurrence of dendritic spikes. Moreover, recent studies have shown interaction between synaptic inputs. We therefore studied the influence of apical tuft input on the integration studied above. We find that excitatory input provides a modulatory influence reducing the capacity of K(A) to suppress synchronized activity, thus facilitating the excitatory drive of oblique dendritic input. Conversely, inhibitory tuft input increases the suppression by K(A) providing a larger control of oblique depolarizing factors on the CA1 pyramidal neuron in terms of what constitutes the most effective level of synchronicity. Furthermore, we show that the selective suppression studied above depends on the conductance of the K(A) channel. K(A) , as several other potassium channels, is modulated by several neuromodulators, for instance acetylcholine and dopamine, both of which have been discussed in relation to learning and memory. We suggest that dendritic conductances and their

  9. Patterns of proteins synthesized in the R15 neuron of Aplysia. Temporal studies and evidence for processing

    PubMed Central

    1976-01-01

    The time-course of changes in the pattern of newly synthesized proteins in the R15 neuron of the parietovisceral ganglion of Aplysia californica has been studied at 14 degrees C. 5% polyacrylamide gels containing sodium dodecyl sulfate (SDS) have been used to separate newly synthesized (leucine-labeled) proteins from the neuron. We have demonstrated that the pattern of newly synthesized proteins from the R15 neuron does not change significantly if 5-h pulses of labeled leucine are given during the first 72 h of in vitro incubation of the excised ganglion. However, the level of leucine incorporation begins to decline somewhere between 17 and 43 h after the ganglion is isolated; at 43 and 69 h the levels of incorporation fell to 29 and 10% of the initial level, respectively. A number of conclusions have been drawn from the use of a sequential, double-label type of experiment in the same cell. There is processing of SDS-soluble, 12,000-dalton (12k) material to 6,000-9,000-dalton (6-9k) material. These materials are the two major peaks on gels after long labeling periods and together account for about 35% of all newly synthesized proteins. After synthesis of 12k material, there is a gradual disappearance of 12k (half-life about 8 h) and simultaneous appearance of 6-9k material on the gels, as the postsynthesis "chase" period of ganglia incubation is increased. The processing of 12k to 6-9k material occurs even in the presence of anisomycin, a protein syntehsis inhibitor, during the chase period. While the rate of 12k to 6-9k conversion can vary from cell to cell, it appears to remain consistent within, and is characteristic of, any individual R15. We detect no circadian rhythm in either the rate of 12k synthesis or the rate of 12k to 6-9k processing with 5-h label periods. These results are discussed in relation to the roles of 12k and 6-9k material in the R15 neuron. PMID:932671

  10. Repeating Spatial-Temporal Motifs of CA3 Activity Dependent on Engineered Inputs from Dentate Gyrus Neurons in Live Hippocampal Networks

    PubMed Central

    Bhattacharya, Aparajita; Desai, Harsh; DeMarse, Thomas B.; Wheeler, Bruce C.; Brewer, Gregory J.

    2016-01-01

    Anatomical and behavioral studies, and in vivo and slice electrophysiology of the hippocampus suggest specific functions of the dentate gyrus (DG) and the CA3 subregions, but the underlying activity dynamics and repeatability of information processing remains poorly understood. To approach this problem, we engineered separate living networks of the DG and CA3 neurons that develop connections through 51 tunnels for axonal communication. Growing these networks on top of an electrode array enabled us to determine whether the subregion dynamics were separable and repeatable. We found spontaneous development of polarized propagation of 80% of the activity in the native direction from DG to CA3 and different spike and burst dynamics for these subregions. Spatial-temporal differences emerged when the relationships of target CA3 activity were categorized with to the number and timing of inputs from the apposing network. Compared to times of CA3 activity when there was no recorded tunnel input, DG input led to CA3 activity bursts that were 7× more frequent, increased in amplitude and extended in temporal envelope. Logistic regression indicated that a high number of tunnel inputs predict CA3 activity with 90% sensitivity and 70% specificity. Compared to no tunnel input, patterns of >80% tunnel inputs from DG specified different patterns of first-to-fire neurons in the CA3 target well. Clustering dendrograms revealed repeating motifs of three or more patterns at up to 17 sites in CA3 that were importantly associated with specific spatial-temporal patterns of tunnel activity. The number of these motifs recorded in 3 min was significantly higher than shuffled spike activity and not seen above chance in control networks in which CA3 was apposed to CA3 or DG to DG. Together, these results demonstrate spontaneous input-dependent repeatable coding of distributed activity in CA3 networks driven by engineered inputs from DG networks. These functional configurations at measured times

  11. Gene Regulatory Mechanisms Underlying the Spatial and Temporal Regulation of Target-Dependent Gene Expression in Drosophila Neurons.

    PubMed

    Berndt, Anthony J E; Tang, Jonathan C Y; Ridyard, Marc S; Lian, Tianshun; Keatings, Kathleen; Allan, Douglas W

    2015-12-01

    Neuronal differentiation often requires target-derived signals from the cells they innervate. These signals typically activate neural subtype-specific genes, but the gene regulatory mechanisms remain largely unknown. Highly restricted expression of the FMRFa neuropeptide in Drosophila Tv4 neurons requires target-derived BMP signaling and a transcription factor code that includes Apterous. Using integrase transgenesis of enhancer reporters, we functionally dissected the Tv4-enhancer of FMRFa within its native cellular context. We identified two essential but discrete cis-elements, a BMP-response element (BMP-RE) that binds BMP-activated pMad, and a homeodomain-response element (HD-RE) that binds Apterous. These cis-elements have low activity and must be combined for Tv4-enhancer activity. Such combinatorial activity is often a mechanism for restricting expression to the intersection of cis-element spatiotemporal activities. However, concatemers of the HD-RE and BMP-RE cis-elements were found to independently generate the same spatiotemporal expression as the Tv4-enhancer. Thus, the Tv4-enhancer atypically combines two low-activity cis-elements that confer the same output from distinct inputs. The activation of target-dependent genes is assumed to 'wait' for target contact. We tested this directly, and unexpectedly found that premature BMP activity could not induce early FMRFa expression; also, we show that the BMP-insensitive HD-RE cis-element is activated at the time of target contact. This led us to uncover a role for the nuclear receptor, seven up (svp), as a repressor of FMRFa induction prior to target contact. Svp is normally downregulated immediately prior to target contact, and we found that maintaining Svp expression prevents cis-element activation, whereas reducing svp gene dosage prematurely activates cis-element activity. We conclude that the target-dependent FMRFa gene is repressed prior to target contact, and that target-derived BMP signaling directly

  12. Gene Regulatory Mechanisms Underlying the Spatial and Temporal Regulation of Target-Dependent Gene Expression in Drosophila Neurons

    PubMed Central

    Ridyard, Marc S.; Lian, Tianshun; Keatings, Kathleen; Allan, Douglas W.

    2015-01-01

    Neuronal differentiation often requires target-derived signals from the cells they innervate. These signals typically activate neural subtype-specific genes, but the gene regulatory mechanisms remain largely unknown. Highly restricted expression of the FMRFa neuropeptide in Drosophila Tv4 neurons requires target-derived BMP signaling and a transcription factor code that includes Apterous. Using integrase transgenesis of enhancer reporters, we functionally dissected the Tv4-enhancer of FMRFa within its native cellular context. We identified two essential but discrete cis-elements, a BMP-response element (BMP-RE) that binds BMP-activated pMad, and a homeodomain-response element (HD-RE) that binds Apterous. These cis-elements have low activity and must be combined for Tv4-enhancer activity. Such combinatorial activity is often a mechanism for restricting expression to the intersection of cis-element spatiotemporal activities. However, concatemers of the HD-RE and BMP-RE cis-elements were found to independently generate the same spatiotemporal expression as the Tv4-enhancer. Thus, the Tv4-enhancer atypically combines two low-activity cis-elements that confer the same output from distinct inputs. The activation of target-dependent genes is assumed to 'wait' for target contact. We tested this directly, and unexpectedly found that premature BMP activity could not induce early FMRFa expression; also, we show that the BMP-insensitive HD-RE cis-element is activated at the time of target contact. This led us to uncover a role for the nuclear receptor, seven up (svp), as a repressor of FMRFa induction prior to target contact. Svp is normally downregulated immediately prior to target contact, and we found that maintaining Svp expression prevents cis-element activation, whereas reducing svp gene dosage prematurely activates cis-element activity. We conclude that the target-dependent FMRFa gene is repressed prior to target contact, and that target-derived BMP signaling directly

  13. Total exertion: zen, psychoanalysis, life.

    PubMed

    Cooper, Paul C

    2011-09-01

    This paper integrates Zen and psychoanalytic concepts; introduces the Zen concept of total exertion; elaborates the profound implications that the notion of total exertion has for the psychoanalytic encounter and the psychotherapist's capacity for maintaining an optimal attentional stance; addresses anxiety-driven interferences to both the psychoanalytic process and deepened Zen practice. Clinical vignettes, personal experiences, poetry and psychoanalytic theory serve to demonstrate the abstract aspects of the discussion.

  14. When exercise causes exertional rhabdomyolysis.

    PubMed

    Furman, Janet

    2015-04-01

    Exertional rhabdomyolysis is a clinical condition caused by intense, repetitive exercise or a sudden increase in exercise in an untrained person, although rhabdomyolysis can occur in trained athletes. In many cases, the presentation of early, uncomplicated rhabdomyolysis is subtle, but serious complications such as renal failure, compartment syndrome, and dysrhythmias may arise if severe exertional rhabdomyolysis is undiagnosed or untreated. Management is further complicated by the lack of concrete management guidelines for treating rhabdomyolysis and returning patients to activity.

  15. Abnormalities of neuronal oscillations and temporal integration to low- and high-frequency auditory stimulation in schizophrenia.

    PubMed

    Hamm, Jordan P; Gilmore, Casey S; Picchetti, Natalie A M; Sponheim, Scott R; Clementz, Brett A

    2011-05-15

    Electroencephalography and magnetoencephalography studies indicate among schizophrenia patients (SZ) abnormal, often reduced, entrained steady-state (aSSR) and transient (N100/M100) neural responses to auditory stimuli. We complement this literature by focusing analyses on auditory cortices, assessing a wide range of stimulation frequencies with long driving periods and evaluating relationships between aSSR and M100 reductions in SZ. Seventeen SZ and 17 healthy subjects (H) participated. Stimuli were 1500 msec binaural broadband noise sequences modulated at 5, 20, 40, 80, or 160 Hz. Magnetoencephalography data were collected and co-registered with structural magnetic resonance images. The aSSRs and M100s projected into brain space were analyzed as a function of hemisphere, stimulus density, and time. For aSSR, SZ displayed weaker entrainment bilaterally at low (5-Hz) and high (80-Hz) modulation frequencies. To 40-Hz stimuli, SZ showed weaker entrainment only in right auditory cortex. For M100, while responses for H increased linearly with stimulus density, this effect was weaker or absent in SZ. A principal components analysis of SZ deficits identified low (5-Hz entrainment and M100) and high (40- to 80-Hz entrainment) frequency components. Discriminant analysis indicated that the low-frequency component uniquely differentiated SZ from H. The high-frequency component correlated with negative symptoms among SZ. The SZ auditory cortices were unable to 1) generate healthy levels of theta and high gamma band (80-Hz) entrainment (aSSR), and 2) augment transient responses (M100s) to rapidly presented auditory information (an index of temporal integration). Only the latter was most apparent in left hemisphere and may reflect a prominent neurophysiological deficit in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Temporal phases of activity-dependent plasticity and memory are mediated by compartmentalized routing of MAPK signaling in aplysia sensory neurons.

    PubMed

    Shobe, Justin L; Zhao, Yali; Stough, Shara; Ye, Xiaojing; Hsuan, Vickie; Martin, Kelsey C; Carew, Thomas J

    2009-01-15

    An activity-dependent form of intermediate memory (AD-ITM) for sensitization is induced in Aplysia by a single tail shock that gives rise to plastic changes (AD-ITF) in tail sensory neurons (SNs) via the interaction of action potential firing in the SN coupled with the release of serotonin in the CNS. Activity-dependent long-term facilitation (AD-LTF, lasting >24hr) requires protein synthesis dependent persistent mitogen-activated protein kinase (MAPK) activation and translocation to the SN nucleus. We now show that the induction of the earlier temporal phase (AD-ITM and AD-ITF), which is translation and transcription independent, requires the activation of a compartmentally distinct novel signaling cascade that links second messengers, MAPK and PKC into a unified pathway within tail SNs. Since both AD-ITM and AD-LTM require MAPK activity, these collective findings suggest that presynaptic SNs route the flow of molecular information to distinct subcellular compartments during the induction of activity-dependent long-lasting memories.

  17. Stereologic estimation of hippocampal GluR2/3- and calretinin-immunoreactive hilar neurons (presumptive mossy cells) in two mouse models of temporal lobe epilepsy.

    PubMed

    Volz, Florian; Bock, Hans H; Gierthmuehlen, Mortimer; Zentner, Josef; Haas, Carola A; Freiman, Thomas M

    2011-09-01

    Hippocampal mossy cells receive dense innervation from dentate granule cells and, in turn, mossy cells innervate both granule cells and interneurons. Mossy cell loss is thought to trigger granule cell mossy fiber sprouting, which may affect granule cell excitability. The aim of this study was to quantify mossy cell loss in two animal models of temporal lobe epilepsy, and determine whether there exists a relationship between mossy cell loss, mossy fiber sprouting, and granule cell dispersion. Representative hippocampal sections from p35 knockout mice and mice with unilateral intrahippocampal kainate injection were immunolabeled for GluR2/3, two subunits of the amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor and calretinin to identify mossy cells. Mossy fibers were immunostained against synaptoporin. p35 Knockout mice showed no hilar cell death, but moderate mossy fiber sprouting and granule cell dispersion. In the kainate-injected hippocampus, there was an 80% and 85% reduction of GluR2/3- and GluR2/3/calretinin-positive hilar neurons, respectively, and dense mossy fiber sprouting and significant granule cell dispersion. In the contralateral hippocampus there was a 52% loss of GluR2/3-, but only a 20% loss of GluR2/3-calretinin-immunoreactive presumptive mossy cells, and granule cell dispersion; no mossy fiber sprouting was observed. These results indicate a probable lack of causality between mossy cell death and mossy fiber sprouting. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  18. Responses to visual contours: spatio-temporal aspects of excitation in the receptive fields of simple striate neurones

    PubMed Central

    Bishop, P. O.; Coombs, J. S.; Henry, G. H.

    1971-01-01

    offset with respect to one another. Most commonly the dark edge centre is slightly in advance of the light edge centre. 6. The discharge peaks in the bimodal and multimodal types come from discharge centres that are spatially separate, each centre firing to only one type of edge. In the case of the bimodal type the light edge centre always lies ahead of the dark edge centre. 7. When a cell responds to a single edge in both directions of movement, the type of contrast effective in one direction is always the reverse of that in the other. When the cell responded in both directions, whether to one or both edges, most commonly a light edge discharge centre in one direction occupied approximately the same location in space as the dark edge centre in the reverse direction and vice versa for the other edge. 8. Temporal aspects of the discharge of simple cells have been examined by recording the responses to moving slits and single edges over a wide range of velocities. ImagesFig. 4Fig. 6 PMID:5157596

  19. Exertional Rhabdomyolysis in the Athlete

    PubMed Central

    Tietze, David C.; Borchers, James

    2014-01-01

    Context: Exertional rhabdomyolysis is a relatively uncommon but potentially fatal condition affecting athletes that requires prompt recognition and appropriate management. Evidence Acquisition: A search of the PubMed database from 2003 to 2013 using the term exertional rhabdomyolysis was performed. Further evaluation of the bibliographies of articles expanded the evidence. Study Design: Clinical review. Level of Evidence: Level 3. Results: Exertional rhabdomyolysis (ER) is a relatively uncommon condition with an incidence of approximately 29.9 per 100,000 patient years but can have very serious consequences of muscle ischemia, cardiac arrhythmia, and death. The athlete will have pain, weakness, and swelling in the muscles affected as well as significantly elevated levels of creatine kinase (CK). Hydration is the foundation for any athlete with ER; management can also include dialysis or surgery. Stratifying the athlete into high- or low-risk categories can determine if further workup is warranted. Conclusion: Exertional rhabdomyolysis evaluation requires a history, physical examination, and serology for definitive diagnosis. Treatment modalities should include rest and hydration. Return to play and future workup should be determined by the risk stratification of the athlete. Strength-of-Recommendation Taxonomy (SORT): C. PMID:24982707

  20. Dopaminergic neurons modulate GABA neuron migration in the embryonic midbrain

    PubMed Central

    Vasudevan, Anju; Won, Chungkil; Li, Suyan; Erdélyi, Ferenc; Szabó, Gábor; Kim, Kwang-Soo

    2012-01-01

    Neuronal migration, a key event during brain development, remains largely unexplored in the mesencephalon, where dopaminergic (DA) and GABA neurons constitute two major neuronal populations. Here we study the migrational trajectories of DA and GABA neurons and show that they occupy ventral mesencephalic territory in a temporally and spatially specific manner. Our results from the Pitx3-deficient aphakia mouse suggest that pre-existing DA neurons modulate GABA neuronal migration to their final destination, providing novel insights and fresh perspectives concerning neuronal migration and connectivity in the mesencephalon in normal as well as diseased brains. PMID:22872083

  1. Dopaminergic neurons modulate GABA neuron migration in the embryonic midbrain.

    PubMed

    Vasudevan, Anju; Won, Chungkil; Li, Suyan; Erdélyi, Ferenc; Szabó, Gábor; Kim, Kwang-Soo

    2012-09-01

    Neuronal migration, a key event during brain development, remains largely unexplored in the mesencephalon, where dopaminergic (DA) and GABA neurons constitute two major neuronal populations. Here we study the migrational trajectories of DA and GABA neurons and show that they occupy ventral mesencephalic territory in a temporally and spatially specific manner. Our results from the Pitx3-deficient aphakia mouse suggest that pre-existing DA neurons modulate GABA neuronal migration to their final destination, providing novel insights and fresh perspectives concerning neuronal migration and connectivity in the mesencephalon in normal as well as diseased brains.

  2. Traction forces exerted by epithelial cell sheets

    NASA Astrophysics Data System (ADS)

    Saez, A.; Anon, E.; Ghibaudo, M.; du Roure, O.; Di Meglio, J.-M.; Hersen, P.; Silberzan, P.; Buguin, A.; Ladoux, B.

    2010-05-01

    Whereas the adhesion and migration of individual cells have been well described in terms of physical forces, the mechanics of multicellular assemblies is still poorly understood. Here, we study the behavior of epithelial cells cultured on microfabricated substrates designed to measure cell-to-substrate interactions. These substrates are covered by a dense array of flexible micropillars whose deflection enables us to measure traction forces. They are obtained by lithography and soft replica molding. The pillar deflection is measured by video microscopy and images are analyzed with home-made multiple particle tracking software. First, we have characterized the temporal and spatial distributions of traction forces of cellular assemblies of various sizes. The mechanical force balance within epithelial cell sheets shows that the forces exerted by neighboring cells strongly depend on their relative position in the monolayer: the largest deformations are always localized at the edge of the islands of cells in the active areas of cell protrusions. The average traction stress rapidly decreases from its maximum value at the edge but remains much larger than the inherent noise due to the force resolution of our pillar tracking software, indicating an important mechanical activity inside epithelial cell islands. Moreover, these traction forces vary linearly with the rigidity of the substrate over about two decades, suggesting that cells exert a given amount of deformation rather than a force. Finally, we engineer micropatterned substrates supporting pillars with anisotropic stiffness. On such substrates cellular growth is aligned with respect to the stiffest direction in correlation with the magnitude of the applied traction forces.

  3. Traction forces exerted by epithelial cell sheets.

    PubMed

    Saez, A; Anon, E; Ghibaudo, M; du Roure, O; Di Meglio, J-M; Hersen, P; Silberzan, P; Buguin, A; Ladoux, B

    2010-05-19

    Whereas the adhesion and migration of individual cells have been well described in terms of physical forces, the mechanics of multicellular assemblies is still poorly understood. Here, we study the behavior of epithelial cells cultured on microfabricated substrates designed to measure cell-to-substrate interactions. These substrates are covered by a dense array of flexible micropillars whose deflection enables us to measure traction forces. They are obtained by lithography and soft replica molding. The pillar deflection is measured by video microscopy and images are analyzed with home-made multiple particle tracking software. First, we have characterized the temporal and spatial distributions of traction forces of cellular assemblies of various sizes. The mechanical force balance within epithelial cell sheets shows that the forces exerted by neighboring cells strongly depend on their relative position in the monolayer: the largest deformations are always localized at the edge of the islands of cells in the active areas of cell protrusions. The average traction stress rapidly decreases from its maximum value at the edge but remains much larger than the inherent noise due to the force resolution of our pillar tracking software, indicating an important mechanical activity inside epithelial cell islands. Moreover, these traction forces vary linearly with the rigidity of the substrate over about two decades, suggesting that cells exert a given amount of deformation rather than a force. Finally, we engineer micropatterned substrates supporting pillars with anisotropic stiffness. On such substrates cellular growth is aligned with respect to the stiffest direction in correlation with the magnitude of the applied traction forces.

  4. Neuronal communication: firing spikes with spikes.

    PubMed

    Brecht, Michael

    2012-08-21

    Spikes of single cortical neurons can exert powerful effects even though most cortical synapses are too weak to fire postsynaptic neurons. A recent study combining single-cell stimulation with population imaging has visualized in vivo postsynaptic firing in genetically identified target cells. The results confirm predictions from in vitro work and might help to understand how the brain reads single-neuron activity.

  5. Imaging calcium in neurons.

    PubMed

    Grienberger, Christine; Konnerth, Arthur

    2012-03-08

    Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.

  6. Passive Synaptic Normalization and Input Synchrony-Dependent Amplification of Cortical Feedback in Thalamocortical Neuron Dendrites

    PubMed Central

    Connelly, William M.; Crunelli, Vincenzo

    2016-01-01

    significantly increase the influence of corticothalamic feedback on sensory information transfer. SIGNIFICANCE STATEMENT Neurons in first-order thalamic nuclei transmit sensory information from the periphery to the cortex. However, the numerically dominant synaptic input to thalamocortical neurons comes from the cortex, which provides a strong, activity-dependent modulatory feedback influence on information flow through the thalamus. Here, we reveal how individual quantal-sized corticothalamic EPSPs propagate within thalamocortical neuron dendrites and how different spatial and temporal input patterns are integrated by these cells. We find that thalamocortical neurons have voltage- and synchrony-dependent postsynaptic mechanisms, involving NMDA receptors and T-type Ca2+ channels that allow nonlinear amplification of integrated corticothalamic EPSPs. These mechanisms significantly increase the responsiveness of thalamocortical neurons to cortical excitatory input and broaden the “modulatory” influence exerted by corticothalamic synapses. PMID:27030759

  7. MiR-218 Induces Neuronal Differentiation of ASCs in a Temporally Sequential Manner with Fibroblast Growth Factor by Regulation of the Wnt Signaling Pathway

    PubMed Central

    Hu, Feihu; Sun, Bo; Xu, Peng; Zhu, Yanliang; Meng, Xian-Hui; Teng, Gao-Jun; Xiao, Zhong-Dang

    2017-01-01

    Differentiation of neural lineages from mesenchymal stem cells has raised the hope of generating functional cells as seed cells for nerve tissue engineering. As important gene regulators, microRNAs (miRNAs) have been speculated to play a vital role in accelerating stem cell differentiation and repairing neuron damage. However, miRNA roles in directing differentiation of stem cells in current protocols are underexplored and the mechanisms of miRNAs as regulators of neuronal differentiation remain ambiguous. In this study, we have determined that miR-218 serves as crucial constituent regulator in neuronal differentiation of adipose stem cells (ASCs) through Wnt signaling pathway based on comprehensive annotation of miRNA sequencing data. Moreover, we have also discovered that miR-218 and Fibroblast Growth Factor-2 (FGF2) modulate neuronal differentiation in a sequential manner. These findings provide additional understanding of the mechanisms regulating stem cell neuronal differentiation as well as a new method for neural lineage differentiation of ASCs. PMID:28045049

  8. Sensitivity to Interaural Time Differences Conveyed in the Stimulus Envelope: Estimating Inputs of Binaural Neurons Through the Temporal Analysis of Spike Trains.

    PubMed

    Dietz, Mathias; Wang, Le; Greenberg, David; McAlpine, David

    2016-08-01

    Sound-source localization in the horizontal plane relies on detecting small differences in the timing and level of the sound at the two ears, including differences in the timing of the modulated envelopes of high-frequency sounds (envelope interaural time differences (ITDs)). We investigated responses of single neurons in the inferior colliculus (IC) to a wide range of envelope ITDs and stimulus envelope shapes. By a novel means of visualizing neural activity relative to different portions of the periodic stimulus envelope at each ear, we demonstrate the role of neuron-specific excitatory and inhibitory inputs in creating ITD sensitivity (or the lack of it) depending on the specific shape of the stimulus envelope. The underlying binaural brain circuitry and synaptic parameters were modeled individually for each neuron to account for neuron-specific activity patterns. The model explains the effects of envelope shapes on sensitivity to envelope ITDs observed in both normal-hearing listeners and in neural data, and has consequences for understanding how ITD information in stimulus envelopes might be maximized in users of bilateral cochlear implants-for whom ITDs conveyed in the stimulus envelope are the only ITD cues available.

  9. Neuronal Mechanisms of Learning and Memory Revealed by Spatial and Temporal Suppression of Neurotransmission Using Shibirets1, a Temperature-Sensitive Dynamin Mutant Gene in Drosophila Melanogaster

    PubMed Central

    Kasuya, Junko; Ishimoto, Hiroshi; Kitamoto, Toshihiro

    2009-01-01

    The fruit fly Drosophila melanogaster is an excellent model organism to identify genes and genetic pathways important for learning and memory. However, its small size makes surgical treatment and electrophysiological manipulation technically difficult, hampering the functional analysis of neuronal circuits that play critical roles in memory processing. To circumvent this problem, we developed a unique experimental strategy that uses the temperature-sensitive allele of the Drosophila dynamin gene, shibirets1 (shits1), in combination with the GAL4/UAS expression system. This strategy allows for rapid and reversible perturbation of synaptic neurotransmission in identifiable neurons, and analysis of the behavioral consequences of such manipulation in free-moving animals. Since its introduction in 2001, this GAL4/UAS-shits1 strategy has been widely used to study the neuronal basis of learning and memory. This review focuses on how this strategy has revitalized Drosophila memory research, and contributed to our understanding of dynamic neuronal processes that control various aspects of memory. PMID:19738923

  10. Structural and Temporal Requirements of Wnt/PCP Protein Vangl2 Function for Convergence and Extension Movements and Facial Branchiomotor Neuron Migration in Zebrafish

    PubMed Central

    Pan, Xiufang; Sittaramane, Vinoth; Gurung, Suman; Chandrasekhar, Anand

    2014-01-01

    Van gogh-like 2 (Vangl2), a core component of the Wnt/Planar Cell Polarity (PCP) signaling pathway, is a four-pass transmembrane protein with N-terminal and C-terminal domains located in the cytosol, and is structurally conserved from flies to mammals. In vertebrates, Vangl2 plays an essential role in convergence and extension (CE) movements during gastrulation and in facial branchiomotor (FBM) neuron migration in the hindbrain. However, the roles of specific Vangl2 domains, of membrane association, and of specific extracellular and intracellular motifs have not been examined, especially in the context of FBM neuron migration. Through heat shock-inducible expression of various Vangl2 transgenes, we found that membrane associated functions of the N-terminal and C-terminal domains of Vangl2 are involved in regulating FBM neuron migration. Importantly, through temperature shift experiments, we found that the critical period for Vangl2 function coincides with the initial stages of FBM neuron migration out of rhombomere 4. Intriguingly, we have also uncovered a putative nuclear localization motif in the C-terminal domain that may play a role in regulating CE movements. PMID:24333599

  11. Temporal resolution of misfolded prion protein transport, accumulation, glial activation, and neuronal death in the retinas of mice inoculated with scrapie

    USDA-ARS?s Scientific Manuscript database

    Currently, there is a lack of pathologic landmarks to describe the progression of prion disease in vivo. The goal of this work was to determine the temporal relationship between the transport of misfolded prion protein from the brain to the retina, the accumulation of PrPSc in the retina, the respon...

  12. Botulinum neurotoxin E (BoNT/E) reduces CA1 neuron loss and granule cell dispersion, with no effects on chronic seizures, in a mouse model of temporal lobe epilepsy.

    PubMed

    Antonucci, Flavia; Di Garbo, Angelo; Novelli, Elena; Manno, Ilaria; Sartucci, Ferdinando; Bozzi, Yuri; Caleo, Matteo

    2008-04-01

    Mesial temporal lobe epilepsy (MTLE) is often the result of an early insult that induces a reorganization in hippocampal circuitry leading, after a latent period, to chronic epilepsy. Hippocampal rearrangements during the latent phase include neuronal loss, axonal and dendritic plasticity, neurogenesis, and cell repositioning, but the role of these changes in epilepsy development is unclear. Here we have tested whether administration of the synaptic blocker botulinum neurotoxin E (BoNT/E) interferes with development of spontaneous seizures and histopathological changes following an episode of status epilepticus (SE). SE was induced by unilateral intrahippocampal injection of kainic acid in mice and BoNT/E was delivered to the same hippocampus 3 h later. We found that treatment with BoNT/E prolonged the duration of the latent period but did not block the occurrence of spontaneous seizures. At the histopathological level, BoNT/E reduced loss of CA1 pyramidal neurons and dispersion of dentate granule cells. Downregulation of reelin expression along the hippocampal fissure was also suppressed by BoNT/E treatment. Our findings indicate that administration of BoNT/E after SE inhibits specific morphological changes in hippocampal circuitry but not the development of spontaneous seizures. This indicates a dissociation between certain anatomical modifications and establishment of chronic epilepsy in MTLE.

  13. Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and no neuronal survival in parahippocampal cortices by long-term post-lesion melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy

    PubMed Central

    Ganjkhani, Mahin; Ali, Rostami; Iraj, Jafari Anarkooli

    2016-01-01

    Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. PMID:27051565

  14. Cystatin C, a cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy.

    PubMed

    Aronica, E; van Vliet, E A; Hendriksen, E; Troost, D; Lopes da Silva, F H; Gorter, J A

    2001-11-01

    Cystatin C (CSTC), a cysteine protease inhibitor, has been implicated in the processes of neuronal degeneration and repair of the nervous system. Using serial analysis of gene expression (SAGE), we recently identified CSTC as one of the genes that are overexpressed after electrically induced status epilepticus (SE). In the present study, Western blot analysis extended the SAGE results, showing increased CSTC protein in the hippocampus and entorhinal cortex. Immunocytochemistry revealed an increase in CSTC expression in glial cells, which was first apparent 24 h after onset of SE, and persisted for at least 3 months. Double immunolabelling confirmed that both reactive astrocytes, and activated microglia were CSTC immunopositive. Within the hippocampus, up-regulation was also observed in neuronal cells within one day after SE. Up-regulation was still present in hippocampal pyramidal cells and surviving interneurons of chronic epileptic rats (3-8 months post-SE). This study demonstrates that status epilepticus leads to a widespread and persistent up-regulation of CSTC in the hippocampus and entorhinal cortex, which may represent an intrinsic neuroprotective mechanism in the course of epileptogenesis that may counteract progression of the disease.

  15. Advances in applications of spiking neuron networks

    NASA Astrophysics Data System (ADS)

    Cios, Krzysztof J.; Sala, Dorel M.

    2000-03-01

    In this paper, we present new findings in constructing and applications of artificial neural networks that use a biologically inspired spiking neuron model. The used model is a point neuron with the interaction between neurons described by postsynaptic potentials. The synaptic plasticity is achieved by using a temporal correlation learning rule, specified as a function of time difference between the firings of pre- and post-synaptic neurons. Using this rule we show how certain associations between neurons in a network of spiking neurons can be implemented. As an example we analyze the dynamic properties of networks of laterally connected spiking neurons and we show their capability to self-organize into topological maps in response to external stimulation. In another application we explore the capability networks of spiking neurons to solve graph algorithms by using temporal coding of distances in a given spatial configuration. The paper underlines the importance of temporal dimension in artificial neural network information processing.

  16. Excitatory projections from the amygdala to neurons in the nucleus pontis oralis in the rat: an intracellular study.

    PubMed

    Xi, M; Fung, S J; Sampogna, S; Chase, M H

    2011-12-01

    There is a consensus that active (REM) sleep (AS) is controlled by cholinergic projections from the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT) to neurons in the nucleus pontis oralis (NPO) that generate AS (i.e. AS-Generator neurons). The present study was designed to provide evidence that other projections to the NPO, such as those from the amygdala, are also capable of inducing AS. Accordingly, the responses of neurons, recorded intracellularly in the NPO, were examined following stimulation of the ipsilateral central nucleus of the amygdala (CNA) in urethane-anesthetized rats. Single pulse stimulation in the CNA produced an early, fast depolarizing potential (EPSP) in neurons within the NPO. The mean latency to the onset of these excitatory postsynaptic potentials (EPSPs) was 3.6±0.2 ms. A late, small-amplitude inhibitory synaptic potential (IPSP) was present following EPSPs in a portion of the NPO neurons. Following stimulation of the CNA with a train of 8-10 pulses, NPO neurons exhibited a sustained depolarization (5-10 mV) of their resting membrane potential. When single subthreshold intracellular depolarizing current pulses were delivered to NPO neurons, CNA-induced EPSPs were sufficient to promote the discharge of these cells. Stimulation of the CNA with a short train of stimuli induced potent temporal facilitation of EPSPs in NPO neurons. Two forms of synaptic plasticity were revealed by the patterns of response of NPO neurons following stimulation of the CNA: paired-pulse facilitation (PPF) and post-tetanic potentiation (PTP). Six of recorded NPO neurons were identified morphologically with neurobiotin. They were medium to large, multipolar cells with diameters >20 μM, which resemble AS-on cells in the NPO. The present results demonstrate that amygdalar projections are capable of exerting a powerful excitatory postsynaptic drive that activates NPO neurons. Therefore, we suggest that the amygdala is capable of inducing AS via direct

  17. Plasticity of neonatal neuronal networks in very premature infants: Source localization of temporal theta activity, the first endogenous neural biomarker, in temporoparietal areas.

    PubMed

    Routier, L; Mahmoudzadeh, M; Panzani, M; Azizollahi, H; Goudjil, S; Kongolo, G; Wallois, F

    2017-01-23

    Temporal theta slow-wave activity (TTA-SW) in premature infants is a specific signature of the early development of temporal networks, as it is observed at the turning point between non-sensory driven spontaneous local processing and cortical network functioning. The role in development and the precise location of TTA-SW remain unknown. Previous studies have demonstrated that preterms from 28 weeks of gestational age (wGA) are able to discriminate phonemes and voice, supporting the idea of a prior genetic structural or activity-dependent fingerprint that would prepare the auditory network to compute auditory information at the onset of thalamocortical connectivity. They recorded TTA-SW in 26-32 wGA preterms. The rate of TTA-SW in response to click stimuli was evaluated using low-density EEG in 30 preterms. The sources of TTA-SW were localized by high-density EEG using different tissues conductivities, head models and mathematical models. They observed that TTA-SW is not sensory driven. Regardless of age, conductivities, head models and mathematical models, sources of TTA-SW were located adjacent to auditory and temporal junction areas. These sources become situated closer to the surface during development. TTA-SW corresponds to spontaneous transient endogenous activities independent of sensory information at this period which might participate in the implementation of auditory, language, memory, attention and or social cognition convergent and does not simply represent a general interaction between the subplate and the cortical plate. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  18. Reflections on the Design of Exertion Games.

    PubMed

    Mueller, Florian Floyd; Altimira, David; Khot, Rohit Ashot

    2015-02-01

    The design of exertion games (i.e., digital games that require physical effort from players) is a difficult intertwined challenge of combining digital games and physical effort. To aid designers in facing this challenge, we describe our experiences of designing exertion games. We outline personal reflections on our design processes and articulate analyses of players' experiences. These reflections and analyses serve to highlight the unique opportunities of combining digital games and physical effort. The insights we seek aim to enhance the understanding of exertion game design, contributing to the advancement of the field, and ultimately resulting in better games and associated player experiences.

  19. Neuronal correlates of decisions to speak and act: Spontaneous emergence and dynamic topographies in a computational model of frontal and temporal areas

    PubMed Central

    Garagnani, Max; Pulvermüller, Friedemann

    2013-01-01

    The neural mechanisms underlying the spontaneous, stimulus-independent emergence of intentions and decisions to act are poorly understood. Using a neurobiologically realistic model of frontal and temporal areas of the brain, we simulated the learning of perception–action circuits for speech and hand-related actions and subsequently observed their spontaneous behaviour. Noise-driven accumulation of reverberant activity in these circuits leads to their spontaneous ignition and partial-to-full activation, which we interpret, respectively, as model correlates of action intention emergence and action decision-and-execution. Importantly, activity emerged first in higher-association prefrontal and temporal cortices, subsequently spreading to secondary and finally primary sensorimotor model-areas, hence reproducing the dynamics of cortical correlates of voluntary action revealed by readiness-potential and verb-generation experiments. This model for the first time explains the cortical origins and topography of endogenous action decisions, and the natural emergence of functional specialisation in the cortex, as mechanistic consequences of neurobiological principles, anatomical structure and sensorimotor experience. PMID:23489583

  20. Online Stimulus Optimization Rapidly Reveals Multidimensional Selectivity in Auditory Cortical Neurons

    PubMed Central

    Hancock, Kenneth E.; Sen, Kamal

    2014-01-01

    Neurons in sensory brain regions shape our perception of the surrounding environment through two parallel operations: decomposition and integration. For example, auditory neurons decompose sounds by separately encoding their frequency, temporal modulation, intensity, and spatial location. Neurons also integrate across these various features to support a unified perceptual gestalt of an auditory object. At higher levels of a sensory pathway, neurons may select for a restricted region of feature space defined by the intersection of multiple, independent stimulus dimensions. To further characterize how auditory cortical neurons decompose and integrate multiple facets of an isolated sound, we developed an automated procedure that manipulated five fundamental acoustic properties in real time based on single-unit feedback in awake mice. Within several minutes, the online approach converged on regions of the multidimensional stimulus manifold that reliably drove neurons at significantly higher rates than predefined stimuli. Optimized stimuli were cross-validated against pure tone receptive fields and spectrotemporal receptive field estimates in the inferior colliculus and primary auditory cortex. We observed, from midbrain to cortex, increases in both level invariance and frequency selectivity, which may underlie equivalent sparseness of responses in the two areas. We found that onset and steady-state spike rates increased proportionately as the stimulus was tailored to the multidimensional receptive field. By separately evaluating the amount of leverage each sound feature exerted on the overall firing rate, these findings reveal interdependencies between stimulus features as well as hierarchical shifts in selectivity and invariance that may go unnoticed with traditional approaches. PMID:24990917

  1. Online stimulus optimization rapidly reveals multidimensional selectivity in auditory cortical neurons.

    PubMed

    Chambers, Anna R; Hancock, Kenneth E; Sen, Kamal; Polley, Daniel B

    2014-07-02

    Neurons in sensory brain regions shape our perception of the surrounding environment through two parallel operations: decomposition and integration. For example, auditory neurons decompose sounds by separately encoding their frequency, temporal modulation, intensity, and spatial location. Neurons also integrate across these various features to support a unified perceptual gestalt of an auditory object. At higher levels of a sensory pathway, neurons may select for a restricted region of feature space defined by the intersection of multiple, independent stimulus dimensions. To further characterize how auditory cortical neurons decompose and integrate multiple facets of an isolated sound, we developed an automated procedure that manipulated five fundamental acoustic properties in real time based on single-unit feedback in awake mice. Within several minutes, the online approach converged on regions of the multidimensional stimulus manifold that reliably drove neurons at significantly higher rates than predefined stimuli. Optimized stimuli were cross-validated against pure tone receptive fields and spectrotemporal receptive field estimates in the inferior colliculus and primary auditory cortex. We observed, from midbrain to cortex, increases in both level invariance and frequency selectivity, which may underlie equivalent sparseness of responses in the two areas. We found that onset and steady-state spike rates increased proportionately as the stimulus was tailored to the multidimensional receptive field. By separately evaluating the amount of leverage each sound feature exerted on the overall firing rate, these findings reveal interdependencies between stimulus features as well as hierarchical shifts in selectivity and invariance that may go unnoticed with traditional approaches.

  2. A model for neurite growth and neuronal morphogenesis.

    PubMed

    Li, G H; Qin, C D

    1996-02-01

    A model is presented for tensile regulation of neuritic growth. It is proposed that the neurite tension can be determined by Hooke's law and determines the growth rate of neurites. The growth of a neurite is defined as the change in its unstretched length. Neuritic growth rate is assumed to increase in proportion to tension magnitude over a certain threshold [Dennerll et al., J. Cell Biol. 107: 665-674 (1988)]. The movement of branch nodes also contributes to the neuronal morphogenesis. It is supposed that the rate of a branch-node displacement is in proportion to the resultant neuritic tension exerted on this node. To deal with the growth-cone movement, it is further supposed that the environment exerts a traction force on the growth cone and the rate of growth-cone displacement is determined by the vector sum of the neuritic tension and the traction force. A group of differential equations are used to describe the model. The key point of the model is that the traction force and the neuritic tension are in opposition to generate a temporal contrast-enhancing mechanism. Results of a simulation study suggest that the model can explain some phenomena related to neuronal morphogenesis.

  3. Neuronal function of the mRNA decapping complex determines survival of Caenorhabditis elegans at high temperature through temporal regulation of heterochronic gene expression.

    PubMed

    Borbolis, Fivos; Flessa, Christina-Maria; Roumelioti, Fani; Diallinas, George; Stravopodis, Dimitrios J; Syntichaki, Popi

    2017-03-01

    In response to adverse environmental cues, Caenorhabditis elegans larvae can temporarily arrest development at the second moult and form dauers, a diapause stage that allows for long-term survival. This process is largely regulated by certain evolutionarily conserved signal transduction pathways, but it is also affected by miRNA-mediated post-transcriptional control of gene expression. The 5'-3' mRNA decay mechanism contributes to miRNA-mediated silencing of target mRNAs in many organisms but how it affects developmental decisions during normal or stress conditions is largely unknown. Here, we show that loss of the mRNA decapping complex activity acting in the 5'-3' mRNA decay pathway inhibits dauer formation at the stressful high temperature of 27.5°C, and instead promotes early developmental arrest. Our genetic data suggest that this arrest phenotype correlates with dysregulation of heterochronic gene expression and an aberrant stabilization of lin-14 mRNA at early larval stages. Restoration of neuronal dcap-1 activity was sufficient to rescue growth phenotypes of dcap-1 mutants at both high and normal temperatures, implying the involvement of common developmental timing mechanisms. Our work unveils the crucial role of 5'-3' mRNA degradation in proper regulation of heterochronic gene expression programmes, which proved to be essential for survival under stressful conditions. © 2017 The Authors.

  4. Neuronal function of the mRNA decapping complex determines survival of Caenorhabditis elegans at high temperature through temporal regulation of heterochronic gene expression

    PubMed Central

    Borbolis, Fivos; Flessa, Christina-Maria; Roumelioti, Fani; Diallinas, George; Stravopodis, Dimitrios J.

    2017-01-01

    In response to adverse environmental cues, Caenorhabditis elegans larvae can temporarily arrest development at the second moult and form dauers, a diapause stage that allows for long-term survival. This process is largely regulated by certain evolutionarily conserved signal transduction pathways, but it is also affected by miRNA-mediated post-transcriptional control of gene expression. The 5′–3′ mRNA decay mechanism contributes to miRNA-mediated silencing of target mRNAs in many organisms but how it affects developmental decisions during normal or stress conditions is largely unknown. Here, we show that loss of the mRNA decapping complex activity acting in the 5′–3′ mRNA decay pathway inhibits dauer formation at the stressful high temperature of 27.5°C, and instead promotes early developmental arrest. Our genetic data suggest that this arrest phenotype correlates with dysregulation of heterochronic gene expression and an aberrant stabilization of lin-14 mRNA at early larval stages. Restoration of neuronal dcap-1 activity was sufficient to rescue growth phenotypes of dcap-1 mutants at both high and normal temperatures, implying the involvement of common developmental timing mechanisms. Our work unveils the crucial role of 5′–3′ mRNA degradation in proper regulation of heterochronic gene expression programmes, which proved to be essential for survival under stressful conditions. PMID:28250105

  5. Somatostatin and Neuropeptide Y Neurons Undergo Different Plasticity in Parahippocampal Regions in Kainic Acid–Induced Epilepsy

    PubMed Central

    Drexel, Meinrad; Kirchmair, Elke; Wieselthaler-Hölzl, Anna; Preidt, Adrian Patrick; Sperk, Günther

    2012-01-01

    Parahippocampal brain areas including the subiculum, presubiculum and parasubiculum, and entorhinal cortex give rise to major input and output neurons of the hippocampus and exert increased excitability in animal models and human temporal lobe epilepsy. Using immunohistochemistry and in situ hybridization for somatostatin and neuropeptide Y, we investigated plastic morphologic and neurochemical changes in parahippocampal neurons in the kainic acid (KA) model of temporal lobe epilepsy. Although constitutively contained in similar subclasses of γ-aminobutyric acid (GABA)-ergic neurons, both neuropeptide systems undergo distinctly different changes in their expression. Somatostatin messenger RNA (mRNA) is rapidly but transiently expressed de novo in pyramidal neurons of the subiculum and entorhinal cortex 24 hours after KA. Surviving somatostatin interneurons display increased mRNA levels at late intervals (3 months) after KA and increased labeling of their terminals in the outer molecular layer of the subiculum; the labeling correlates with the number of spontaneous seizures, suggesting that the seizures may trigger somatostatin expression. In contrast, neuropeptide Y mRNA is consistently expressed in principal neurons of the proximal subiculum and the lateral entorhinal cortex and labeling for the peptide persistently increased in virtually all major excitatory pathways of the hippocampal formation. The pronounced plastic changes differentially involving both neuropeptide systems indicate marked rearrangement of parahippocampal areas, presumably aiming at endogenous seizure protection. Their receptors may be targets for anticonvulsive drug therapy. PMID:22437342

  6. STDP in Recurrent Neuronal Networks

    PubMed Central

    Gilson, Matthieu; Burkitt, Anthony; van Hemmen, J. Leo

    2010-01-01

    Recent results about spike-timing-dependent plasticity (STDP) in recurrently connected neurons are reviewed, with a focus on the relationship between the weight dynamics and the emergence of network structure. In particular, the evolution of synaptic weights in the two cases of incoming connections for a single neuron and recurrent connections are compared and contrasted. A theoretical framework is used that is based upon Poisson neurons with a temporally inhomogeneous firing rate and the asymptotic distribution of weights generated by the learning dynamics. Different network configurations examined in recent studies are discussed and an overview of the current understanding of STDP in recurrently connected neuronal networks is presented. PMID:20890448

  7. Silicon Neuron.

    DTIC Science & Technology

    Many researchers have developed neural architectures based on extremely simplified models of neurons . Recently, researchers have developed an analog...electronic model of a neuron that more accurately reproduces its biological counterpart. This electronic neuron was designed to emulate the ionic...currents present in biological neurons . Based on this neural model, we designed and fabricated an eight input neuron on a 2mm by 2mm 40 pin VLSI (very

  8. The Critical Role of Golgi Cells in Regulating Spatio-Temporal Integration and Plasticity at the Cerebellum Input Stage

    PubMed Central

    D'Angelo, Egidio

    2008-01-01

    The discovery of the Golgi cell is bound to the foundation of the Neuron Doctrine. Recently, the excitable mechanisms of this inhibitory interneuron have been investigated with modern experimental and computational techniques raising renewed interest for the implications it might have for cerebellar circuit functions. Golgi cells are pacemakers with preferential response frequency and phase-reset in the theta-frequency band and can therefore impose specific temporal dynamics to granule cell responses. Moreover, through their connectivity, Golgi cells determine the spatio-temporal organization of cerebellar activity. Finally, Golgi cells, by controlling granule cell depolarization and NMDA channel unblock, regulate the induction of long-term synaptic plasticity at the mossy fiber – granule cell synapse. Thus, the Golgi cells can exert an extensive control on spatio-temporal signal organization and information storage in the granular layer playing a critical role for cerebellar computation. PMID:18982105

  9. Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo

    PubMed Central

    Taylor, Hannah; Schmiedt, Joscha T.; Çarçak, Nihan; Onat, Filiz; Di Giovanni, Giuseppe; Lambert, Régis; Leresche, Nathalie; Crunelli, Vincenzo; David, Francois

    2014-01-01

    Background The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity. New method and results We demonstrate that optogenetics and silicone probe recordings can be combined with intracerebral reverse microdialysis for the long-term delivery of neuroactive drugs around the optic fiber and silicone probe. In particular, we show the effect of antagonists of T-type Ca2+ channels, hyperpolarization-activated cyclic nucleotide-gated channels and metabotropic glutamate receptors on silicone probe-recorded activity of the local opsin-transfected neurons in the ventrobasal thalamus, and demonstrate the changes that the block of these thalamic channels/receptors brings about in the network dynamics of distant somatotopic cortical neuronal ensembles. Comparison with existing methods This is the first demonstration of successfully combining optogenetics and neuronal ensemble recordings with reverse microdialysis. This combination of techniques overcomes some of the disadvantages that are associated with the use of intracerebral injection of a drug-containing solution at the site of laser activation. Conclusions The combination of reverse microdialysis, silicone probe recordings and optogenetics can unravel the short and long-term effects of specific transmitter- and voltage-gated channels on laser-modulated firing at the site of optogenetic stimulation and the actions that

  10. Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo.

    PubMed

    Taylor, Hannah; Schmiedt, Joscha T; Carçak, Nihan; Onat, Filiz; Di Giovanni, Giuseppe; Lambert, Régis; Leresche, Nathalie; Crunelli, Vincenzo; David, Francois

    2014-09-30

    The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity. We demonstrate that optogenetics and silicone probe recordings can be combined with intracerebral reverse microdialysis for the long-term delivery of neuroactive drugs around the optic fiber and silicone probe. In particular, we show the effect of antagonists of T-type Ca(2+) channels, hyperpolarization-activated cyclic nucleotide-gated channels and metabotropic glutamate receptors on silicone probe-recorded activity of the local opsin-transfected neurons in the ventrobasal thalamus, and demonstrate the changes that the block of these thalamic channels/receptors brings about in the network dynamics of distant somatotopic cortical neuronal ensembles. This is the first demonstration of successfully combining optogenetics and neuronal ensemble recordings with reverse microdialysis. This combination of techniques overcomes some of the disadvantages that are associated with the use of intracerebral injection of a drug-containing solution at the site of laser activation. The combination of reverse microdialysis, silicone probe recordings and optogenetics can unravel the short and long-term effects of specific transmitter- and voltage-gated channels on laser-modulated firing at the site of optogenetic stimulation and the actions that these manipulations exert on distant neuronal populations. Copyright © 2014

  11. The force exerted by a fireball

    SciTech Connect

    Makrinich, G.; Fruchtman, A.

    2014-02-15

    The force exerted by a fireball was deduced both from the change of the equilibrium position of a pendulum and from the change in the pendulum oscillation period. That measured force was found to be several times larger than the force exerted by the ions accelerated across the double layer that is assumed to surround the fireball. The force enhancement that is expected by ion-neutral collisions in the fireball is evaluated to be too small to explain the measured enhanced force. Gas pressure increase, due to gas heating through electron-neutral collisions, as recently suggested [Stenzel et al., J. Appl. Phys. 109, 113305 (2011)], is examined as the source for the force enhancement.

  12. Exertional leg pain: teasing out arterial entrapments.

    PubMed

    Pham, Thomas T; Kapur, Rahul; Harwood, Marc I

    2007-12-01

    Vascular causes of exertional lower extremity pain are relatively rare, but may be the answer in athletes refractory to treatment for the more common overuse syndromes of the lower extremities. It is important to differentiate these vascular causes from chronic exertional compartment syndrome (CECS), medial tibial stress syndrome (MTSS), and stress fractures in order to develop appropriate treatment plans, avoid complications, and return athletes to play expeditiously. Important vascular etiologies to be considered are popliteal artery entrapment syndrome (PAES), endofibrotic disease, popliteal artery aneurysm, cystic adventitial disease, and peripheral arterial dissections. The diagnostic workup involves angiography or noninvasive vascular studies such as Doppler ultrasound or magnetic resonance angiography in both the neutral and provocative positions. Treatment of these vascular abnormalities typically involves surgical correction of the vascular anomaly.

  13. Myeloperoxidase Exerts Microbicidal Activity against Mycobacterium tuberculosis

    PubMed Central

    Borelli, Violetta; Banfi, Elena; Perrotta, Maria Giovanna; Zabucchi, Giuliano

    1999-01-01

    We investigated the antimycobacterial role of myeloperoxidase (MPO), one of the most abundant granule proteins in human neutrophils. Our data indicate that purified MPO, in the presence of hydrogen peroxide, exerts a consistent killing activity against Mycobacterium tuberculosis H37Rv and against a clinical isolate. The activity is time and dose dependent and requires the presence of chloride ions in the assay medium. PMID:10417186

  14. The Role of Wnt/β-Catenin Signaling Pathway in Disrupted Hippocampal Neurogenesis of Temporal Lobe Epilepsy: A Potential Therapeutic Target?

    PubMed

    Huang, Cheng; Fu, Xiang-Hui; Zhou, Dong; Li, Jin-Mei

    2015-07-01

    Temporal lobe epilepsy is one of the most common clinical neurological disorders. One of the major pathological findings in temporal lobe epilepsy is hippocampal sclerosis, characterized by massive neuronal loss and severe gliosis. The epileptogenesis process of temporal lobe epilepsy usually starts with initial precipitating insults, followed by neurodegeneration, abnormal hippocampus circuitry reorganization, and the formation of hypersynchronicity. Experimental and clinical evidence strongly suggests that dysfunctional neurogenesis is involved in the epileptogenesis. Recent data demonstrate that neurogenesis is induced by acute seizures or precipitating insults, whereas the capacity of neuronal recruitment and proliferation substantially decreases in the chronic phase of epilepsy. Participation of the Wnt/β-catenin signaling pathway in neurogenesis reveals its importance in epileptogenesis; its dysfunction contributes to the structural and functional abnormality of temporal lobe epilepsy, while rescuing this pathway exerts neuroprotective effects. Here, we summarize data supporting the involvement of Wnt/β-catenin signaling in the epileptogenesis of temporal lobe epilepsy. We also propose that the Wnt/β-catenin signaling pathway may serve as a promising therapeutic target for temporal lobe epilepsy treatment.

  15. Forces exerted during microneurosurgery: a cadaver study

    PubMed Central

    Marcus, Hani J; Zareinia, Kourosh; Gan, Liu Shi; Yang, Fang Wei; Lama, Sanju; Yang, Guang-Zhong; Sutherland, Garnette R

    2014-01-01

    Background A prerequisite for the successful design and use of robots in neurosurgery is knowledge of the forces exerted by surgeons during neurosurgical procedures. The aim of the present cadaver study was to measure the surgical instrument forces exerted during microneurosurgery. Methods An experimental apparatus was set up consisting of a platform for human cadaver brains, a Leica microscope to provide illumination and magnification, and a Quanser 6 Degrees-Of-Freedom Telepresence System for tissue manipulation and force measurements. Results The measured forces varied significantly depending on the region of the brain (P = 0.016) and the maneuver performed (P < 0.0001). Moreover, blunt arachnoid dissection was associated with greater force exertion than sharp dissection (0.22 N vs. 0.03 N; P = 0.001). Conclusions The forces necessary to manipulate brain tissue were surprisingly low and varied depending on the anatomical structure being manipulated, and the maneuver performed. Knowledge of such forces could well increase the safety of microsurgery. © 2014 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons, Ltd. PMID:24431265

  16. Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease.

    PubMed

    Shinko, Aiko; Agari, Takashi; Kameda, Masahiro; Yasuhara, Takao; Kondo, Akihiko; Tayra, Judith Thomas; Sato, Kenichiro; Sasaki, Tatsuya; Sasada, Susumu; Takeuchi, Hayato; Wakamori, Takaaki; Borlongan, Cesario V; Date, Isao

    2014-01-01

    In clinical practice, deep brain stimulation (DBS) is effective for treatment of motor symptoms in Parkinson's disease (PD). However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS). We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz) with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH)-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF) was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the effectiveness

  17. Temporal prediction errors modulate cingulate-insular coupling.

    PubMed

    Limongi, Roberto; Sutherland, Steven C; Zhu, Jian; Young, Michael E; Habib, Reza

    2013-05-01

    Prediction error (i.e., the difference between the expected and the actual event's outcome) mediates adaptive behavior. Activity in the anterior mid-cingulate cortex (aMCC) and in the anterior insula (aINS) is associated with the commission of prediction errors under uncertainty. We propose a dynamic causal model of effective connectivity (i.e., neuronal coupling) between the aMCC, the aINS, and the striatum in which the task context drives activity in the aINS and the temporal prediction errors modulate extrinsic cingulate-insular connections. With functional magnetic resonance imaging, we scanned 15 participants when they performed a temporal prediction task. They observed visual animations and predicted when a stationary ball began moving after being contacted by another moving ball. To induced uncertainty-driven prediction errors, we introduced spatial gaps and temporal delays between the balls. Classical and Bayesian fMRI analyses provided evidence to support that the aMCC-aINS system along with the striatum not only responds when humans predict whether a dynamic event occurs but also when it occurs. Our results reveal that the insula is the entry port of a three-region pathway involved in the processing of temporal predictions. Moreover, prediction errors rather than attentional demands, task difficulty, or task duration exert an influence in the aMCC-aINS system. Prediction errors debilitate the effect of the aMCC on the aINS. Finally, our computational model provides a way forward to characterize the physiological parallel of temporal prediction errors elicited in dynamic tasks.

  18. Virtual exertions: evoking the sense of exerting forces in virtual reality using gestures and muscle activity.

    PubMed

    Chen, Karen B; Ponto, Kevin; Tredinnick, Ross D; Radwin, Robert G

    2015-06-01

    This study was a proof of concept for virtual exertions, a novel method that involves the use of body tracking and electromyography for grasping and moving projections of objects in virtual reality (VR). The user views objects in his or her hands during rehearsed co-contractions of the same agonist-antagonist muscles normally used for the desired activities to suggest exerting forces. Unlike physical objects, virtual objects are images and lack mass. There is currently no practical physically demanding way to interact with virtual objects to simulate strenuous activities. Eleven participants grasped and lifted similar physical and virtual objects of various weights in an immersive 3-D Cave Automatic Virtual Environment. Muscle activity, localized muscle fatigue, ratings of perceived exertions, and NASA Task Load Index were measured. Additionally, the relationship between levels of immersion (2-D vs. 3-D) was studied. Although the overall magnitude of biceps activity and workload were greater in VR, muscle activity trends and fatigue patterns for varying weights within VR and physical conditions were the same. Perceived exertions for varying weights were not significantly different between VR and physical conditions. Perceived exertion levels and muscle activity patterns corresponded to the assigned virtual loads, which supported the hypothesis that the method evoked the perception of physical exertions and showed that the method was promising. Ultimately this approach may offer opportunities for research and training individuals to perform strenuous activities under potentially safer conditions that mimic situations while seeing their own body and hands relative to the scene. © 2014, Human Factors and Ergonomics Society.

  19. Activities of visual cortical and hippocampal neurons co-fluctuate in freely moving rats during spatial behavior

    PubMed Central

    Haggerty, Daniel Christopher; Ji, Daoyun

    2015-01-01

    Visual cues exert a powerful control over hippocampal place cell activities that encode external spaces. The functional interaction of visual cortical neurons and hippocampal place cells during spatial navigation behavior has yet to be elucidated. Here we show that, like hippocampal place cells, many neurons in the primary visual cortex (V1) of freely moving rats selectively fire at specific locations as animals run repeatedly on a track. The V1 location-specific activity leads hippocampal place cell activity both spatially and temporally. The precise activities of individual V1 neurons fluctuate every time the animal travels through the track, in a correlated fashion with those of hippocampal place cells firing at overlapping locations. The results suggest the existence of visual cortical neurons that are functionally coupled with hippocampal place cells for spatial processing during natural behavior. These visual neurons may also participate in the formation and storage of hippocampal-dependent memories. DOI: http://dx.doi.org/10.7554/eLife.08902.001 PMID:26349031

  20. Cold thermoregulatory responses following exertional fatigue.

    PubMed

    Castellani, John W; Sawka, Michael N; DeGroot, David W; Young, Andrew J

    2010-06-01

    Participants in prolonged, physically demanding cold-weather activities are at risk for a condition called "thermoregulatory fatigue". During cold exposure, the increased gradient favoring body heat loss to the environment is opposed by physiological responses and clothing and behavioral strategies that conserve body heat stores to defend body temperature. The primary human physiological responses elicited by cold exposure are shivering and peripheral vasoconstriction. Shivering increases thermogenesis and replaces body heat losses, while peripheral vasoconstriction improves thermal insulation of the body and retards the rate of heat loss. A body of scientific literature supports the concept that prolonged and/or repeated cold exposure, fatigue induced by sustained physical exertion, or both together, can impair the shivering and vasoconstrictor responses to cold ("thermoregulatory fatigue"). The mechanisms accounting for this thermoregulatory impairment are not clear, but there is evidence to suggest that changes in central thermoregulatory control or peripheral sympathetic responsiveness to cold lead to thermoregulatory fatigue and increased susceptibility to hypothermia.

  1. [Neuronal ageing].

    PubMed

    Piechota, Małgorzata; Sunderland, Piotr

    2014-01-01

    Ageing leads to irreversible alterations in the nervous system, which to various extent impair its functions such as capacity to learn and memory. In old neurons and brain, similarly to what may take place in other cells, there is increased oxidative stress, disturbed energetic homeostasis and metabolism, accumulation of damage in proteins and nucleic acids. Characteristic of old neurons are alterations in plasticity, synaptic transmission, sensitivity to neurotrophic factors and cytoskeletal changes. Some markers of senescence, whose one of them is SA-beta-galactosidase were used to show the process of neuronal ageing both in vitro, and in vivo. Some research suggest that, despite the fact that neurons are postmitotic cells, it is cell cycle proteins which play a certain role in their biology, e.g. differentiation. However, their role in neuronal ageing is not known or explained. Ageing is the serious factor of development of neurodegenerative diseases among others Alzheimer disease.

  2. 20 CFR 220.132 - Physical exertion requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Physical exertion requirements. 220.132... ACT DETERMINING DISABILITY Vocational Considerations § 220.132 Physical exertion requirements. To determine the physical exertion requirements of work in the national economy, jobs are classified as...

  3. Differentiated Ratings of Perceived Exertion during Physical Exercise

    DTIC Science & Technology

    1982-01-01

    MEDICINE AND SCIENCE IN SPORTS AND EXERCISE VOl 14, No 5. Pp 397-405. 1982 -1982 Differentiated ratings of perceived exertion during physical ...that PANDOLF, KENT B. Differentiated ratings of perceived exertion utilizes differentiated ratings of perceived exertion (RPE) during physical exercise ...in the eval- Specific instructions and procedures for the utilization uation of effort sensations during physical exercise . Ekblom and Goldbarg (17

  4. Perceived Exertion of the PACER in High School Students

    ERIC Educational Resources Information Center

    Smith, John D.; Holmes, Patricia A.

    2013-01-01

    The purpose of this study was to explore high school students' perceived exertion after participating in the Progressive Aerobic Cardiovascular Endurance Run (PACER). Immediately after completing the PACER, students (N = 792) indicated their perceived exertion on the OMNI rating of perceived exertion (RPE) for children (1-10 scale). All students,…

  5. Synchronization by elastic neuronal latencies

    NASA Astrophysics Data System (ADS)

    Vardi, Roni; Timor, Reut; Marom, Shimon; Abeles, Moshe; Kanter, Ido

    2013-01-01

    Psychological and physiological considerations entail that formation and functionality of neuronal cell assemblies depend upon synchronized repeated activation such as zero-lag synchronization. Several mechanisms for the emergence of this phenomenon have been suggested, including the global network quantity, the greatest common divisor of neuronal circuit delay loops. However, they require strict biological prerequisites such as precisely matched delays and connectivity, and synchronization is represented as a stationary mode of activity instead of a transient phenomenon. Here we show that the unavoidable increase in neuronal response latency to ongoing stimulation serves as a nonuniform gradual stretching of neuronal circuit delay loops. This apparent nuisance is revealed to be an essential mechanism in various types of neuronal time controllers, where synchronization emerges as a transient phenomenon and without predefined precisely matched synaptic delays. These findings are described in an experimental procedure where conditioned stimulations were enforced on a circuit of neurons embedded within a large-scale network of cortical cells in vitro, and are corroborated and extended by simulations of circuits composed of Hodgkin-Huxley neurons with time-dependent latencies. These findings announce a cortical time scale for time controllers based on tens of microseconds stretching of neuronal circuit delay loops per spike. They call for a reexamination of the role of the temporal periodic mode in brain functionality using advanced in vitro and in vivo experiments.

  6. Capacity of a single spiking neuron

    NASA Astrophysics Data System (ADS)

    Ikeda, Shiro; Manton, Jonathan H.

    2009-12-01

    It is widely believed the neurons transmit information in the form of spikes. Since the spike patterns are known to be noisy, the neuron information channel is noisy. We have investigated the channel capacity of this "Spiking neuron channel" for both of the "temporal coding" and the "rate coding," which are two main coding considered in the neuroscience [1, 2]. As the result, we've proved that the distribution of inputs, which achieves the channel capacity, is a discrete distribution with finite mass points for temporal and rate coding under a reasonable assumption. In this draft, we show the details of the proof.

  7. The definition of exertion-related cardiac events.

    PubMed

    Rai, M; Thompson, P D

    2011-02-01

    Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

  8. Time-warp-invariant neuronal processing.

    PubMed

    Gütig, Robert; Sompolinsky, Haim

    2009-07-01

    Fluctuations in the temporal durations of sensory signals constitute a major source of variability within natural stimulus ensembles. The neuronal mechanisms through which sensory systems can stabilize perception against such fluctuations are largely unknown. An intriguing instantiation of such robustness occurs in human speech perception, which relies critically on temporal acoustic cues that are embedded in signals with highly variable duration. Across different instances of natural speech, auditory cues can undergo temporal warping that ranges from 2-fold compression to 2-fold dilation without significant perceptual impairment. Here, we report that time-warp-invariant neuronal processing can be subserved by the shunting action of synaptic conductances that automatically rescales the effective integration time of postsynaptic neurons. We propose a novel spike-based learning rule for synaptic conductances that adjusts the degree of synaptic shunting to the temporal processing requirements of a given task. Applying this general biophysical mechanism to the example of speech processing, we propose a neuronal network model for time-warp-invariant word discrimination and demonstrate its excellent performance on a standard benchmark speech-recognition task. Our results demonstrate the important functional role of synaptic conductances in spike-based neuronal information processing and learning. The biophysics of temporal integration at neuronal membranes can endow sensory pathways with powerful time-warp-invariant computational capabilities.

  9. Time-Warp–Invariant Neuronal Processing

    PubMed Central

    Gütig, Robert; Sompolinsky, Haim

    2009-01-01

    Fluctuations in the temporal durations of sensory signals constitute a major source of variability within natural stimulus ensembles. The neuronal mechanisms through which sensory systems can stabilize perception against such fluctuations are largely unknown. An intriguing instantiation of such robustness occurs in human speech perception, which relies critically on temporal acoustic cues that are embedded in signals with highly variable duration. Across different instances of natural speech, auditory cues can undergo temporal warping that ranges from 2-fold compression to 2-fold dilation without significant perceptual impairment. Here, we report that time-warp–invariant neuronal processing can be subserved by the shunting action of synaptic conductances that automatically rescales the effective integration time of postsynaptic neurons. We propose a novel spike-based learning rule for synaptic conductances that adjusts the degree of synaptic shunting to the temporal processing requirements of a given task. Applying this general biophysical mechanism to the example of speech processing, we propose a neuronal network model for time-warp–invariant word discrimination and demonstrate its excellent performance on a standard benchmark speech-recognition task. Our results demonstrate the important functional role of synaptic conductances in spike-based neuronal information processing and learning. The biophysics of temporal integration at neuronal membranes can endow sensory pathways with powerful time-warp–invariant computational capabilities. PMID:19582146

  10. Negative radiation pressure exerted on kinks

    NASA Astrophysics Data System (ADS)

    Forgács, Péter; Lukács, Árpád; Romańczukiewicz, Tomasz

    2008-06-01

    The interaction of a kink and a monochromatic plane wave in one dimensional scalar field theories is studied. It is shown that in a large class of models the radiation pressure exerted on the kink is negative, i.e. the kink is pulled towards the source of the radiation. This effect has been observed by numerical simulations in the ϕ4 model, and it is explained by a perturbative calculation assuming that the amplitude of the incoming wave is small. Quite importantly the effect is shown to be robust against small perturbations of the ϕ4 model. In the sine-Gordon (SG) model the time-averaged radiation pressure acting on the kink turns out to be zero. The results of the perturbative computations in the SG model are shown to be in full agreement with an analytical solution corresponding to the superposition of a SG kink with a cnoidal wave. It is also demonstrated that the acceleration of the kink satisfies Newton’s law.

  11. Exercise Device Would Exert Selectable Constant Resistance

    NASA Technical Reports Server (NTRS)

    Smith, Damon C.

    2003-01-01

    An apparatus called the resistive exercise device (RED) has been proposed to satisfy a requirement for exercise equipment aboard the International Space Station (ISS) that could passively exert a selectable constant load on both the outward and return strokes. The RED could be used alone; alternatively, the RED could be used in combination with another apparatus called the treadmill with vibration isolation and stabilization (TVIS), in which case the combination would be called the subject load device (SLD). The basic RED would be a passive device, but it could incorporate an electric motor to provide eccentric augmentation (augmentation to make the load during inward movement greater than the load during outward movement). The RED concept represents a unique approach to providing a constant but selectable resistive load for exercise for the maintenance and development of muscles. Going beyond the original ISS application, the RED could be used on Earth as resistive weight training equipment. The advantage of the RED over conventional weight-lifting equipment is that it could be made portable and lightweight.

  12. Negative radiation pressure exerted on kinks

    SciTech Connect

    Forgacs, Peter; Lukacs, Arpad; Romanczukiewicz, Tomasz

    2008-06-15

    The interaction of a kink and a monochromatic plane wave in one dimensional scalar field theories is studied. It is shown that in a large class of models the radiation pressure exerted on the kink is negative, i.e. the kink is pulled towards the source of the radiation. This effect has been observed by numerical simulations in the {phi}{sup 4} model, and it is explained by a perturbative calculation assuming that the amplitude of the incoming wave is small. Quite importantly the effect is shown to be robust against small perturbations of the {phi}{sup 4} model. In the sine-Gordon (SG) model the time-averaged radiation pressure acting on the kink turns out to be zero. The results of the perturbative computations in the SG model are shown to be in full agreement with an analytical solution corresponding to the superposition of a SG kink with a cnoidal wave. It is also demonstrated that the acceleration of the kink satisfies Newton's law.

  13. A short upstream promoter region mediates transcriptional regulation of the mouse doublecortin gene in differentiating neurons

    PubMed Central

    2010-01-01

    Background Doublecortin (Dcx), a MAP (Microtubule-Associated Protein), is transiently expressed in migrating and differentiating neurons and thereby characterizes neuronal precursors and neurogenesis in developing and adult neurogenesis. In addition, reduced Dcx expression during development has been related to appearance of brain pathologies. Here, we attempt to unveil the molecular mechanisms controlling Dcx gene expression by studying its transcriptional regulation during neuronal differentiation. Results To determine and analyze important regulatory sequences of the Dcx promoter, we studied a putative regulatory region upstream from the mouse Dcx coding region (pdcx2kb) and several deletions thereof. These different fragments were used in vitro and in vivo to drive reporter gene expression. We demonstrated, using transient expression experiments, that pdcx2kb is sufficient to control specific reporter gene expression in cerebellar cells and in the developing brain (E14.5). We determined the temporal profile of Dcx promoter activity during neuronal differentiation of mouse embryonic stem cells (mESC) and found that transcriptional activation of the Dcx gene varies along with neuronal differentiation of mESC. Deletion experiments and sequence comparison of Dcx promoters across rodents, human and chicken revealed the importance of a highly conserved sequence in the proximal region of the promoter required for specific and strong expression in neuronal precursors and young neuronal cells. Further analyses revealed the presence in this short sequence of several conserved, putative transcription factor binding sites: LEF/TCF (Lymphoid Enhancer Factor/T-Cell Factor) which are effectors of the canonical Wnt pathway; HNF6/OC2 (Hepatocyte Nuclear Factor-6/Oncecut-2) members of the ONECUT family and NF-Y/CAAT (Nuclear Factor-Y). Conclusions Studies of Dcx gene regulatory sequences using native, deleted and mutated constructs suggest that fragments located upstream of the

  14. [Impact of opiates on dopaminergic neurons].

    PubMed

    Kaufling, Jennifer; Freund-Mercier, Marie-José; Barrot, Michel

    2016-01-01

    Since the work of Johnson and North, it is known that opiates increase the activity of dopaminergic neurons by a GABA neuron-mediated desinhibition. This model should however be updated based on recent advances. Thus, the neuroanatomical location of the GABA neurons responsible for this desinhibition has been recently detailed: they belong to a brain structure in continuity with the posterior part of the ventral tegmental area and discovered this past decade. Other data also highlighted the critical role played by glutamatergic transmission in the opioid regulation of dopaminergic neuron activity. During protracted opiate withdrawal, the inhibitory/excitatory balance exerted on dopaminergic neurons is altered. These results are now leading to propose an original hypothesis for explaining the impact of protracted opiate withdrawal on mood.

  15. Bifurcating neuron: characterization and dynamics

    NASA Astrophysics Data System (ADS)

    Farhat, Nabil H.; Eldefrawy, Mostafa H.

    1993-02-01

    We discuss the concept of bifurcating neuron and show it combines functional complexity, comparable to that of the living (biological) neuron, with structural simplicity and power efficiency which are important attributes for its hardware realizations, both optoelectronic or electronic. The functional complexity of the bifurcating neuron is key to removing many limitations of present-day neural networks which employ predominantly sigmoidal neurons that can not account for the temporal relations of firing instances of neurons in a network. In the language of information processing, accounting for such temporal relations is synonymous with retention of phase information. The complex behavior of the bifurcating neuron is characterized. It is shown to be capable of exhibiting phase-locking and synchronization, and that it exhibits a host of firing modalities that parallel those observed by neurophysiologists in the living neuron including chaotic firing and that it is capable of bifurcating between these firing modalities depending on the nature of its input. The implications of this complex behavior for the introduction of a new generation of bifurcating neural networks, that are capable of using chaos as adaptive intrinsic noise, for self-annealing and directed intelligent search of the phase-space of bifurcating networks are discussed. It is argued that the bifurcating neuron concept is key to building new physical structures (bifurcating networks) in which one can study the roles of bifurcation, synchronicity, and chaos in collective nonlinear dynamical signal processing and is moreover key to modeling and understanding higher-level cortical signal processing such as feature-binding and cognition, and that its ease of implementation in analog hardware promises to offer important technological benefits.

  16. Temporal predictability enhances auditory detection

    PubMed Central

    Lawrance, Emma L. A.; Harper, Nicol S.; Cooke, James E.; Schnupp, Jan W. H.

    2015-01-01

    Periodic stimuli are common in natural environments and are ecologically relevant, for example, footsteps and vocalizations. This study reports a detectability enhancement for temporally cued, periodic sequences. Target noise bursts (embedded in background noise) arriving at the time points which followed on from an introductory, periodic “cue” sequence were more easily detected (by ~1.5 dB SNR) than identical noise bursts which randomly deviated from the cued temporal pattern. Temporal predictability and corresponding neuronal “entrainment” have been widely theorized to underlie important processes in auditory scene analysis and to confer perceptual advantage. This is the first study in the auditory domain to clearly demonstrate a perceptual enhancement of temporally predictable, near-threshold stimuli. PMID:24907846

  17. Temporal predictability enhances auditory detection.

    PubMed

    Lawrance, Emma L A; Harper, Nicol S; Cooke, James E; Schnupp, Jan W H

    2014-06-01

    Periodic stimuli are common in natural environments and are ecologically relevant, for example, footsteps and vocalizations. This study reports a detectability enhancement for temporally cued, periodic sequences. Target noise bursts (embedded in background noise) arriving at the time points which followed on from an introductory, periodic "cue" sequence were more easily detected (by ∼1.5 dB SNR) than identical noise bursts which randomly deviated from the cued temporal pattern. Temporal predictability and corresponding neuronal "entrainment" have been widely theorized to underlie important processes in auditory scene analysis and to confer perceptual advantage. This is the first study in the auditory domain to clearly demonstrate a perceptual enhancement of temporally predictable, near-threshold stimuli.

  18. Stochastic phase-change neurons.

    PubMed

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals.

  19. Stochastic phase-change neurons

    NASA Astrophysics Data System (ADS)

    Tuma, Tomas; Pantazi, Angeliki; Le Gallo, Manuel; Sebastian, Abu; Eleftheriou, Evangelos

    2016-08-01

    Artificial neuromorphic systems based on populations of spiking neurons are an indispensable tool in understanding the human brain and in constructing neuromimetic computational systems. To reach areal and power efficiencies comparable to those seen in biological systems, electroionics-based and phase-change-based memristive devices have been explored as nanoscale counterparts of synapses. However, progress on scalable realizations of neurons has so far been limited. Here, we show that chalcogenide-based phase-change materials can be used to create an artificial neuron in which the membrane potential is represented by the phase configuration of the nanoscale phase-change device. By exploiting the physics of reversible amorphous-to-crystal phase transitions, we show that the temporal integration of postsynaptic potentials can be achieved on a nanosecond timescale. Moreover, we show that this is inherently stochastic because of the melt-quench-induced reconfiguration of the atomic structure occurring when the neuron is reset. We demonstrate the use of these phase-change neurons, and their populations, in the detection of temporal correlations in parallel data streams and in sub-Nyquist representation of high-bandwidth signals.

  20. The Effect of Exertion on Heart Rate and Rating of Perceived Exertion in Acutely Concussed Individuals.

    PubMed

    Hinds, Andrea; Leddy, John; Freitas, Michael; Czuczman, Natalie; Willer, Barry

    2016-08-01

    Research suggests that one physiological effect of concussion is a disruption in regulation of autonomic nervous system control that affects the balance between parasympathetic and sympathetic output. While changes in heart rate after concussion have been observed, the nature of the heart rate change during progressive exercise has not been well evaluated in acutely symptomatic patients. Additionally, little is known about the relationship between HR and RPE in this population. We compared changes in heart rate and perceived effort during graded treadmill exertion in recently concussed patients to elucidate the effect of brain injury on cardiovascular response to exercise. Resting HR, HR on exercise initiation, and changes in HR and RPE during the Buffalo Concussion Treadmill Test (BCTT) were compared on two test visits: When patients were symptomatic (acute) and after recovery. Results were compared with the test-retest results obtained from a control group consisting of healthy, non-concussed individuals. Patients had a significantly lower HR at onset of exercise when acutely concussed as compared to when recovered and reported greater perceived exertion at every exercise intensity level when symptomatic, despite exercising at lower workloads, than when recovered. Sympathetic response to increased exertion was not affected by concussion - HR increased in response to exercise at a comparable rate in both tests. These differences observed in response to exercise between the first BCTT and follow-up evaluation in initially concussed patients were not present in non-concussed individuals. Our results suggest that during the acute phase after concussion, acutely concussed patients demonstrated an impaired ability to shift from parasympathetic to sympathetic control over heart rate at the onset of exercise. Changes in the autonomic nervous system after concussion may be more complex than previously reported. Continued evaluation of autonomic regulatory effects in the

  1. The Effect of Exertion on Heart Rate and Rating of Perceived Exertion in Acutely Concussed Individuals

    PubMed Central

    Hinds, Andrea; Leddy, John; Freitas, Michael; Czuczman, Natalie; Willer, Barry

    2016-01-01

    Objective Research suggests that one physiological effect of concussion is a disruption in regulation of autonomic nervous system control that affects the balance between parasympathetic and sympathetic output. While changes in heart rate after concussion have been observed, the nature of the heart rate change during progressive exercise has not been well evaluated in acutely symptomatic patients. Additionally, little is known about the relationship between HR and RPE in this population. Methods We compared changes in heart rate and perceived effort during graded treadmill exertion in recently concussed patients to elucidate the effect of brain injury on cardiovascular response to exercise. Resting HR, HR on exercise initiation, and changes in HR and RPE during the Buffalo Concussion Treadmill Test (BCTT) were compared on two test visits: When patients were symptomatic (acute) and after recovery. Results were compared with the test-retest results obtained from a control group consisting of healthy, non-concussed individuals. Results Patients had a significantly lower HR at onset of exercise when acutely concussed as compared to when recovered and reported greater perceived exertion at every exercise intensity level when symptomatic, despite exercising at lower workloads, than when recovered. Sympathetic response to increased exertion was not affected by concussion - HR increased in response to exercise at a comparable rate in both tests. These differences observed in response to exercise between the first BCTT and follow-up evaluation in initially concussed patients were not present in non-concussed individuals. Conclusion Our results suggest that during the acute phase after concussion, acutely concussed patients demonstrated an impaired ability to shift from parasympathetic to sympathetic control over heart rate at the onset of exercise. Changes in the autonomic nervous system after concussion may be more complex than previously reported. Continued evaluation of

  2. Calcium signals in olfactory neurons.

    PubMed

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  3. Addictive neurons

    PubMed Central

    Kodirov, Sodikdjon A.

    2017-01-01

    Since the reward center is considered to be the area tegmentalis ventralis of the hypothalamus, logically its neurons could mainly be responsible for addiction. However, the literature asserts that almost any neurons of CNS can respond to one or another addictive compound. Obviously not only addictive nicotine, but also alcohol, amphetamine, cannabis, cocaine, heroin and morphine may influence dopaminergic cells alone in VTA. Moreover, paradoxically some of these drugs ameliorate symptoms, counterbalance syndromes, cure diseases and improve health, not only those related to the CNS and in adults, but also almost all other organs and in children, e.g. epilepsy. PMID:28649663

  4. MRI of neuronal plasticity in rodent models.

    PubMed

    Pelled, Galit

    2011-01-01

    Modifications in the behavior and architecture of neuronal networks are well documented to occur in association with learning and memory, as well as following injury. These plasticity mechanisms are crucial to ensure adequate processing of stimuli, and they also dictate the degree of recovery following peripheral or central nervous system injury. Nevertheless, the underlying neuronal mechanisms that determine the degree of plasticity of neuronal pathways are not fully understood. Recent developments in animal-dedicated magnetic resonance imaging (MRI) scanners and related hardware afford a high spatial and temporal resolution, making functional MRI and manganese-enhanced MRI emerging tools for studying reorganization of neuronal pathways in rodent models. Many of the observed changes in neuronal functions in rodent's brains following injury discussed here agree with clinical human fMRI findings. This demonstrates that animal model imaging can have a significant clinical impact in the neuronal plasticity and rehabilitation arenas.

  5. Transition in subicular burst firing neurons from epileptiform activity to suppressed state by feedforward inhibition.

    PubMed

    Sah, Nirnath; Sikdar, Sujit K

    2013-08-01

    The subiculum, a para-hippocampal structure positioned between the cornu ammonis 1 subfield and the entorhinal cortex, has been implicated in temporal lobe epilepsy in human patients and in animal models of epilepsy. The structure is characterized by the presence of a significant population of burst firing neurons that has been shown previously to lead epileptiform activity locally. Phase transitions in epileptiform activity in neurons following a prolonged challenge with an epileptogenic stimulus has been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of phase transitions in the burst firing neurons of the subiculum in an in vitro rat brain slice model of epileptogenesis. Whole-cell patch-clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable state was followed by a late suppressed state upon continuous perfusion with epileptogenic 4-aminopyridine and magnesium-free medium. The suppressed state was characterized by inhibitory post-synaptic potentials in pyramidal excitatory neurons and bursting activity in local fast-spiking interneurons at a frequency of 0.1-0.8 Hz. The inhibitory post-synaptic potentials were mediated by GABAA receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These inhibitory post-synaptic potentials ceased following a cut between the cornu ammonis 1 and subiculum. The suppression of epileptiform activity in the subiculum thus represents a homeostatic response towards the induced hyperexcitability. Our results suggest the importance of feedforward inhibition in exerting this homeostatic control.

  6. Force Exertion Capacity Measurements in Haptic Virtual Environments

    ERIC Educational Resources Information Center

    Munih, Marko; Bardorfer, Ales; Ceru, Bojan; Bajd, Tadej; Zupan, Anton

    2010-01-01

    An objective test for evaluating functional status of the upper limbs (ULs) in patients with muscular distrophy (MD) is presented. The method allows for quantitative assessment of the UL functional state with an emphasis on force exertion capacity. The experimental measurement setup and the methodology for the assessment of maximal exertable force…

  7. Exertional Rhabdomyolysis: What Is It and Why Should We Care?

    ERIC Educational Resources Information Center

    Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

    2012-01-01

    Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a…

  8. 20 CFR 220.135 - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... limitations. (a) General. The claimant's impairment(s) and related symptoms, such as pain, may cause... as pain, are exertional, nonexertional, or a combination of both. (b) Exertional limitations. When... pain, affect only the claimant's ability to meet the strength demands of jobs (sitting,...

  9. 20 CFR 220.135 - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... limitations. (a) General. The claimant's impairment(s) and related symptoms, such as pain, may cause... as pain, are exertional, nonexertional, or a combination of both. (b) Exertional limitations. When... pain, affect only the claimant's ability to meet the strength demands of jobs (sitting,...

  10. 20 CFR 220.135 - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... limitations. (a) General. The claimant's impairment(s) and related symptoms, such as pain, may cause... as pain, are exertional, nonexertional, or a combination of both. (b) Exertional limitations. When... pain, affect only the claimant's ability to meet the strength demands of jobs (sitting,...

  11. 20 CFR 220.135 - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... limitations. (a) General. The claimant's impairment(s) and related symptoms, such as pain, may cause... as pain, are exertional, nonexertional, or a combination of both. (b) Exertional limitations. When... pain, affect only the claimant's ability to meet the strength demands of jobs (sitting,...

  12. Using Ratings of Perceived Exertion in Physical Education

    ERIC Educational Resources Information Center

    Lagally, Kristen M.

    2013-01-01

    Ratings of perceived exertion have been shown to be a valid method of monitoring physical activity intensity for both adults and children. As such, this subjective method may serve as an alternative to objective measurements for assessing students' performance on national standards 2 and 4. The OMNI-Child perceived exertion scales were…

  13. Exertional Rhabdomyolysis: What Is It and Why Should We Care?

    ERIC Educational Resources Information Center

    Thomas, David Q.; Carlson, Kelli A.; Marzano, Amy; Garrahy, Deborah

    2012-01-01

    Exertional rhabdomyolysis gained increased attention recently when 13 football players from the University of Iowa developed this condition after an especially demanding practice session and were hospitalized. Exertional rhabdomyolysis may lead to severe kidney stress, kidney failure, and even sudden death. Anyone who does physical exercise at a…

  14. Using Ratings of Perceived Exertion in Physical Education

    ERIC Educational Resources Information Center

    Lagally, Kristen M.

    2013-01-01

    Ratings of perceived exertion have been shown to be a valid method of monitoring physical activity intensity for both adults and children. As such, this subjective method may serve as an alternative to objective measurements for assessing students' performance on national standards 2 and 4. The OMNI-Child perceived exertion scales were…

  15. Acute exertional anterior compartment syndrome in an adolescent female.

    PubMed

    Fehlandt, A; Micheli, L

    1995-01-01

    Acute compartment syndromes usually occur as a complication of major trauma. While the chronic exertional anterior tibial compartment syndrome is well described in the sports medicine literature, reports of acute tibial compartment syndromes due to physical exertion, or repetitive microtrauma, are rare. The case of an adolescent female who developed an acute anterior compartment syndrome from running in a soccer game is described in this report. Failure to recognize the onset of an acute exertional compartment syndrome may lead to treatment delay and serious complications. Whereas the chronic exertional anterior compartment syndrome is characterized by pain that diminishes with the cessation of exercise, the onset of the acute exertional anterior compartment syndrome is heralded by pain that continues, or increases, after exercise has stopped. Compartment pressure measurement confirms the clinical diagnosis and helps guide treatment. True compartment syndromes require urgent fasciotomy.

  16. Backpropagation ANN-based prediction of exertional heat illness.

    PubMed

    Aggarwal, Yogender; Karan, Bhuwan Mohan; Das, Barda Nand; Aggarwal, Tarana; Sinha, Rakesh Kumar

    2007-12-01

    Exertional heat illness is primarily a multi-system disorder results from the combined effect of exertional and thermoregulation stress. The severity of exertional heat illness can be classified as mild, intermediate and severe from non-specific symptoms like thirst, myalgia, poor concentration, hysteria, vomiting, weakness, cramps, impaired judgement, headache, diarrhea, fatigue, hyperventilation, anxiety, and nausea to more severe symptoms like exertional dehydration, heat cramps, heat exhaustion, heat injury, heatstroke, rhabdomyolysis, and acute renal failure. At its early stage, it is quite difficult to find out the severity of disease with manual screening because of overlapping of symptoms. Therefore, one need to classify automatically the disease based on symptoms. The 7:10:1 backpropagation artificial neural network model has been used to predict the clinical outcome from the symptoms that are routinely available to clinicians. The model has found to be effective in differentiating the different stages of exertional heat-illness with an overall performance of 100%.

  17. Exertional myopathy in whooping cranes (Grus americana) with prognostic guidlelines

    USGS Publications Warehouse

    Hanley, C.S.; Thomas, N.J.; Paul-Murphy, P.; Hartup, B.K.

    2005-01-01

    Exertional myopathy developed in three whooping cranes (Grus americana) secondary to routine capture, handling, and trauma. Presumptive diagnosis of exertional myopathy was based on history of recent capture or trauma, clinical signs, and elevation of aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, and serum potassium. Treatments were attempted in each case, but ultimately were not successful. Gross and microscopic lesions at necropsy confirmed the diagnosis in each case, with the leg musculature most severely affected. Guidelines for determining prognosis of exertional myopathy in cranes have been included based on the analysis of these cases and others in the literature. As treatment is largely unrewarding, prevention remains the key in controlling exertional myopathy. Identification of predisposing factors and proper handling, immobilization, and transportation techniques can help prevent development of exertional myopathy in cranes.

  18. Exertional myopathy in whooping cranes (Grus americana) with prognostic guidelines.

    PubMed

    Hanley, Christopher S; Thomas, Nancy J; Paul-Murphy, Joanne; Hartup, Barry K

    2005-09-01

    Exertional myopathy developed in three whooping cranes (Grus americana) secondary to routine capture, handling, and trauma. Presumptive diagnosis of exertional myopathy was based on history of recent capture or trauma, clinical signs, and elevation of aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, and serum potassium. Treatments were attempted in each case, but ultimately were not successful. Gross and microscopic lesions at necropsy confirmed the diagnosis in each case, with the leg musculature most severely affected. Guidelines for determining prognosis of exertional myopathy in cranes have been included based on the analysis of these cases and others in the literature. As treatment is largely unrewarding, prevention remains the key in controlling exertional myopathy. Identification of predisposing factors and proper handling, immobilization, and transportation techniques can help prevent development of exertional myopathy in cranes.

  19. Sudden synchrony leaps accompanied by frequency multiplications in neuronal activity

    PubMed Central

    Vardi, Roni; Goldental, Amir; Guberman, Shoshana; Kalmanovich, Alexander; Marmari, Hagar; Kanter, Ido

    2013-01-01

    A classical view of neural coding relies on temporal firing synchrony among functional groups of neurons, however, the underlying mechanism remains an enigma. Here we experimentally demonstrate a mechanism where time-lags among neuronal spiking leap from several tens of milliseconds to nearly zero-lag synchrony. It also allows sudden leaps out of synchrony, hence forming short epochs of synchrony. Our results are based on an experimental procedure where conditioned stimulations were enforced on circuits of neurons embedded within a large-scale network of cortical cells in vitro and are corroborated by simulations of neuronal populations. The underlying biological mechanisms are the unavoidable increase of the neuronal response latency to ongoing stimulations and temporal or spatial summation required to generate evoked spikes. These sudden leaps in and out of synchrony may be accompanied by multiplications of the neuronal firing frequency, hence offering reliable information-bearing indicators which may bridge between the two principal neuronal coding paradigms. PMID:24198764

  20. Dietary polyphenols exert neuroprotective effects by attenuating neuronal and astrocytic damage in cerebral ischemia

    USDA-ARS?s Scientific Manuscript database

    Polyphenols are natural substances with variable phenolic structures and are found in vegetables, fruits, grains, bark, roots, tea, and wine. There are over 8000 polyphenolic structures identified in plants, but edible plants contain only several hundred polyphenolic structures. Recent interest in...

  1. Temporal networks

    NASA Astrophysics Data System (ADS)

    Holme, Petter; Saramäki, Jari

    2012-10-01

    A great variety of systems in nature, society and technology-from the web of sexual contacts to the Internet, from the nervous system to power grids-can be modeled as graphs of vertices coupled by edges. The network structure, describing how the graph is wired, helps us understand, predict and optimize the behavior of dynamical systems. In many cases, however, the edges are not continuously active. As an example, in networks of communication via e-mail, text messages, or phone calls, edges represent sequences of instantaneous or practically instantaneous contacts. In some cases, edges are active for non-negligible periods of time: e.g., the proximity patterns of inpatients at hospitals can be represented by a graph where an edge between two individuals is on throughout the time they are at the same ward. Like network topology, the temporal structure of edge activations can affect dynamics of systems interacting through the network, from disease contagion on the network of patients to information diffusion over an e-mail network. In this review, we present the emergent field of temporal networks, and discuss methods for analyzing topological and temporal structure and models for elucidating their relation to the behavior of dynamical systems. In the light of traditional network theory, one can see this framework as moving the information of when things happen from the dynamical system on the network, to the network itself. Since fundamental properties, such as the transitivity of edges, do not necessarily hold in temporal networks, many of these methods need to be quite different from those for static networks. The study of temporal networks is very interdisciplinary in nature. Reflecting this, even the object of study has many names-temporal graphs, evolving graphs, time-varying graphs, time-aggregated graphs, time-stamped graphs, dynamic networks, dynamic graphs, dynamical graphs, and so on. This review covers different fields where temporal graphs are considered

  2. Temporal resolution of PrPSc transport, PrPSc accumulation, activation of glia and neuronal death in retinas from C57Bl/6 mice inoculated with RML scrapie: Relevance to biomarkers of prion disease progression

    USDA-ARS?s Scientific Manuscript database

    Currently, there is a lack of pathologic landmarks to objectively evaluate the progression of prion disease in vivo. The goal of this work was to determine the temporal relationship between transport of misfolded prion protein to the retina from the brain, accumulation of PrPSc in the retina, the re...

  3. Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain

    PubMed Central

    Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

    2013-01-01

    Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system. PMID:24009718

  4. Cellular neuron and large wireless neural network

    NASA Astrophysics Data System (ADS)

    Jannson, Tomasz; Forrester, Thomas; Ambrose, Barry; Kazantzidis, Matheos; Lin, Freddie

    2006-05-01

    A new approach to neural networks is proposed, based on wireless interconnects (synapses) and cellular neurons, both software and hardware; with the capacity of 10 10 neurons, almost fully connected. The core of the system is Spatio-Temporal-Variant (STV) kernel and cellular axon with synaptic plasticity variable in time and space. The novel large neural network hardware is based on two established wireless technologies: RF-cellular and IR-wireless.

  5. Island cells control temporal association memory.

    PubMed

    Kitamura, Takashi; Pignatelli, Michele; Suh, Junghyup; Kohara, Keigo; Yoshiki, Atsushi; Abe, Kuniya; Tonegawa, Susumu

    2014-02-21

    Episodic memory requires associations of temporally discontiguous events. In the entorhinal-hippocampal network, temporal associations are driven by a direct pathway from layer III of the medial entorhinal cortex (MECIII) to the hippocampal CA1 region. However, the identification of neural circuits that regulate this association has remained unknown. In layer II of entorhinal cortex (ECII), we report clusters of excitatory neurons called island cells, which appear in a curvilinear matrix of bulblike structures, directly project to CA1, and activate interneurons that target the distal dendrites of CA1 pyramidal neurons. Island cells suppress the excitatory MECIII input through the feed-forward inhibition to control the strength and duration of temporal association in trace fear memory. Together, the two EC inputs compose a control circuit for temporal association memory.

  6. Prior Acute Mental Exertion in Exercise and Sport

    PubMed Central

    Silva-Júnior, Fernando Lopes e; Emanuel, Patrick; Sousa, Jordan; Silva, Matheus; Teixeira, Silmar; Pires, Flávio; Machado, Sérgio; Arias-Carrion, Oscar

    2016-01-01

    Introduction: Mental exertion is a psychophysiological state caused by sustained and prolonged cognitive activity. The understanding of the possible effects of acute mental exertion on physical performance, and their physiological and psychological responses are of great importance for the performance of different occupations, such as military, construction workers, athletes (professional or recreational) or simply practicing regular exercise, since these occupations often combine physical and mental tasks while performing their activities. However, the effects of implementation of a cognitive task on responses to aerobic exercise and sports are poorly understood. Our narrative review aims to provide information on the current research related to the effects of prior acute mental fatigue on physical performance and their physiological and psychological responses associated with exercise and sports. Methods: The literature search was conducted using the databases PubMed, ISI Web of Knowledge and PsycInfo using the following terms and their combinations: “mental exertion”, “mental fatigue”, “mental fatigue and performance”, “mental exertion and sports” “mental exertion and exercise”. Results: We concluded that prior acute mental exertion affects effectively the physiological and psychophysiological responses during the cognitive task, and performance in exercise. Conclusion: Additional studies involving prior acute mental exertion, exercise/sports and physical performance still need to be carried out in order to analyze the physiological, psychophysiological and neurophysiological responses subsequently to acute mental exertion in order to identify cardiovascular factors, psychological, neuropsychological associates. PMID:27867415

  7. Orexin (hypocretin)/dynorphin neurons control GABAergic inputs to tuberomammillary neurons.

    PubMed

    Eriksson, Krister S; Sergeeva, Olga A; Selbach, Oliver; Haas, Helmut L

    2004-03-01

    High activity of the histaminergic neurons in the tuberomammillary (TM) nucleus increases wakefulness, and their firing rate is highest during waking and lowest during rapid eye movement sleep. The TM neurons receive a prominent innervation from sleep-active gamma-aminobutyric acidergic (GABAergic) neurons in the ventrolateral preoptic nucleus, which inhibits them during sleep. They also receive an excitatory input from the orexin- and dynorphin-containing neurons in the lateral hypothalamus, which are critically involved in sleep regulation and whose dysfunction causes narcolepsy. We have used intracellular recordings and immunohistochemistry to study if orexin neurons exert control over the GABAergic inputs to TM neurons in rat hypothalamic slices. Dynorphin suppressed GABAergic inputs and thus disinhibits the TM neurons, acting in concert with orexin to increase the excitability of these neurons. In contrast, both orexin-A and orexin-B markedly increased the frequency of GABAergic potentials, while co-application of orexin and dynorphin produced responses similar to dynorphin alone. Thus, orexins excite TM neurons directly and by disinhibition, gated by dynorphin. These data might explain some of the neuropathology of narcolepsy.

  8. Arthropod toxins acting on neuronal potassium channels.

    PubMed

    Jiménez-Vargas, Juana María; Possani, Lourival D; Luna-Ramírez, Karen

    2017-09-20

    Arthropod venoms are a rich mixture of biologically active compounds exerting different physiological actions across diverse phyla and affecting multiple organ systems including the central nervous system. Venom compounds can inhibit or activate ion channels, receptors and transporters with high specificity and affinity providing essential insights into ion channel function. In this review, we focus on arthropod toxins (scorpions, spiders, bees and centipedes) acting on neuronal potassium channels. A brief description of the K(+) channels classification and structure is included and a compendium of neuronal K(+) channels and the arthropod toxins that modify them have been listed. Copyright © 2017. Published by Elsevier Ltd.

  9. Understanding the Mismatch Between Coaches' and Players' Perceptions of Exertion.

    PubMed

    Brink, Michel S; Kersten, Anna W; Frencken, Wouter G P

    2017-04-01

    A mismatch between the training exertion intended by a coach and the exertion perceived by players is well established in sports. However, it is unknown whether coaches can accurately observe exertion of individual players during training. Furthermore, the discrepancy in coaches' and players' perceptions has not been explained. To determine the relation between intended and observed training exertion by the coach and perceived training exertion by the players and establish whether on-field training characteristics, intermittent endurance capacity, and maturity status explain the mismatch. During 2 mesocycles of 4 wk (in November and March), rating of intended exertion (RIE), rating of observed exertion (ROE), and rating of perceived exertion (RPE) were monitored in 31 elite young soccer players. External and internal training loads were objectively quantified with accelerometers (PlayerLoad) and heart-rate monitors (TRIMPmod). Results of an interval shuttle-run test (ISRT) and age at peak height velocity (APHV) were determined for all players. RIE, ROE, and RPE were monitored in 977 training sessions. The correlations between RIE and RPE (r = .58; P < .01) and between ROE and RPE (r = .64; P < .01) were moderate. The mean difference between RIE and RPE was -0.31 ± 1.99 and between ROE and RPE was -0.37 ± 1.87. Multilevel analyses showed that PlayerLoad and ISRT predicted RIE and ROE. Coaches base their intended and observed exertion on what they expect players will do and what they actually did on the field. When doing this, they consider the intermittent endurance capacity of individual players.

  10. Signal propagation through feedforward neuronal networks with different operational modes

    NASA Astrophysics Data System (ADS)

    Li, Jie; Liu, Feng; Xu, Ding; Wang, Wei

    2009-02-01

    How neuronal activity is propagated across multiple layers of neurons is a fundamental issue in neuroscience. Using numerical simulations, we explored how the operational mode of neurons —coincidence detector or temporal integrator— could affect the propagation of rate signals through a 10-layer feedforward network with sparse connectivity. Our study was based on two kinds of neuron models. The Hodgkin-Huxley (HH) neuron can function as a coincidence detector, while the leaky integrate-and-fire (LIF) neuron can act as a temporal integrator. When white noise is afferent to the input layer, rate signals can be stably propagated through both networks, while neurons in deeper layers fire synchronously in the absence of background noise; but the underlying mechanism for the development of synchrony is different. When an aperiodic signal is presented, the network of HH neurons can represent the temporal structure of the signal in firing rate. Meanwhile, synchrony is well developed and is resistant to background noise. In contrast, rate signals are somewhat distorted during the propagation through the network of LIF neurons, and only weak synchrony occurs in deeper layers. That is, coincidence detectors have a performance advantage over temporal integrators in propagating rate signals. Therefore, given weak synaptic conductance and sparse connectivity between layers in both networks, synchrony does greatly subserve the propagation of rate signals with fidelity, and coincidence detection could be of considerable functional significance in cortical processing.

  11. [Acute cardiovascular complications of vigorous physical exertion by untrained persons].

    PubMed

    Hart, H Ch; Hart, W

    2002-08-10

    Physical exertion has paradoxical effects: regular physical activity offers protection against cardiovascular diseases, but, on the other hand, it has been shown that strenuous exercise can provoke coronary heart disease and sudden death. The risks of vigorous exertion apply particularly to untrained individuals and persons with a sedentary lifestyle. Physical exertion can cause a myocardial infarction or sudden death in people who were considered perfectly healthy before this event. In most cases, the mechanism of this is probably a rupture at the site of a vulnerable atherosclerotic plaque, with local activation of coagulation. Disturbances in cardiac rhythm may also be a cause of these complications.

  12. Neurons other than motor neurons in motor neuron disease.

    PubMed

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  13. Supplementary Motor Area exerts Proactive and Reactive Control of Arm Movements

    PubMed Central

    Chen, Xiaomo; Scangos, Katherine Wilson; Stuphorn, Veit

    2010-01-01

    Adaptive behavior requires the ability to flexibly control actions. This can occur either proactively to anticipate task requirements, or reactively in response to sudden changes. Here we report neuronal activity in the supplementary motor area (SMA) that is correlated with both forms of behavioral control. Single and multi-unit activity and intracranial local field potentials (LFP) were recorded in macaque monkeys during a stop signal task, which elicits both proactive and reactive behavioral control. The LFP power in high (60-150 Hz) and low (25-40 Hz) frequency bands was significantly correlated with arm movement reaction time, starting before target onset. Multi- and single unit activity also showed a significant regression with reaction time. In addition, LFPs, multi- and single unit activity changed their activity level depending on the trial history, mirroring adjustments on the behavioral level. Together, these findings indicate that neuronal activity in the SMA exerts proactive control of arm movements by adjusting the level of motor readiness. On trials when the monkeys successfully canceled arm movements in response to an unforeseen stop signal, the LFP power particularly in a low (10-50 Hz) frequency range increased early enough to be causally related to the inhibition of the arm movement on those trials. This indicated that neuronal activity in the SMA is also involved in response inhibition in reaction to sudden task changes. Our findings indicate therefore that SMA plays a role in the proactive control of motor readiness and the reactive inhibition of unwanted movements. PMID:21048123

  14. Selective extracellular stimulation of individual neurons in ganglia

    NASA Astrophysics Data System (ADS)

    Lu, Hui; Chestek, Cynthia A.; Shaw, Kendrick M.; Chiel, Hillel J.

    2008-09-01

    Selective control of individual neurons could clarify neural functions and aid disease treatments. To target specific neurons, it may be useful to focus on ganglionic neuron clusters, which are found in the peripheral nervous system in vertebrates. Because neuron cell bodies are found primarily near the surface of invertebrate ganglia, and often found near the surface of vertebrate ganglia, we developed a technique for controlling individual neurons extracellularly using the buccal ganglia of the marine mollusc Aplysia californica as a model system. We experimentally demonstrated that anodic currents can selectively activate an individual neuron and cathodic currents can selectively inhibit an individual neuron using this technique. To define spatial specificity, we studied the minimum currents required for stimulation, and to define temporal specificity, we controlled firing frequencies up to 45 Hz. To understand the mechanisms of spatial and temporal specificity, we created models using the NEURON software package. To broadly predict the spatial specificity of arbitrary neurons in any ganglion sharing similar geometry, we created a steady-state analytical model. A NEURON model based on cat spinal motor neurons showed responses to extracellular stimulation qualitatively similar to those of the Aplysia NEURON model, suggesting that this technique could be widely applicable to vertebrate and human peripheral ganglia having similar geometry.

  15. Evoking prescribed spike times in stochastic neurons

    NASA Astrophysics Data System (ADS)

    Doose, Jens; Lindner, Benjamin

    2017-09-01

    Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

  16. Use of Human Neurons Derived via Cellular Reprogramming Methods to Study Host-Parasite Interactions of Toxoplasma gondii in Neurons.

    PubMed

    Halonen, Sandra K

    2017-09-23

    Toxoplasma gondii is an intracellular protozoan parasite, with approximately one-third of the worlds' population chronically infected. In chronically infected individuals, the parasite resides in tissue cysts in neurons in the brain. The chronic infection in immunocompetant individuals has traditionally been considered to be asymptomatic, but increasing evidence indicates that chronic infection is associated with diverse neurological disorders such as schizophrenia, cryptogenic epilepsy, and Parkinson's Disease. The mechanisms by which the parasite exerts affects on behavior and other neuronal functions are not understood. Human neurons derived from cellular reprogramming methods offer the opportunity to develop better human neuronal models to study T. gondii in neurons. Results from two studies using human neurons derived via cellular reprogramming methods indicate these human neuronal models provide better in vitro models to study the effects of T. gondii on neurons and neurological functions. In this review, an overview of the current neural reprogramming methods will be given, followed by a summary of the studies using human induced pluripotent stem cell (hiPSC)-derived neurons and induced neurons (iNs) to study T. gondii in neurons. The potential of these neural reprogramming methods for further study of the host-parasite interactions of T. gondii in neurons will be discussed.

  17. Herpes encephalitis preceded by ipsilateral vestibular neuronitis.

    PubMed

    Philpot, Stephen J; Archer, John S

    2005-11-01

    A 74-year-old woman developed vertigo and jerk nystagmus to the left with normal cerebral imaging. Three days later she developed fever, altered mental state and left medial temporal lobe hypodensity, confirmed on lumbar puncture to be due to herpes simplex type 1 encephalitis. We propose that the patient had vestibular neuronitis caused by HSV-1 that progressed to ipsilateral temporal lobe encephalitis.

  18. Fractional differentiation by neocortical pyramidal neurons

    PubMed Central

    Lundstrom, Brian Nils; Higgs, Matthew H; Spain, William J; Fairhall, Adrienne L

    2008-01-01

    Neural systems adapt to changes in stimulus statistics. However, it is not known how stimuli with complex temporal dynamics drive the dynamics of adaptation and the resulting firing rate. For single neurons, it has often been assumed that adaptation has a single time scale. Here, we show that single rat neocortical pyramidal neurons adapt with a time scale that depends on the time scale of changes in stimulus statistics. This multiple time scale adaptation is consistent with fractional order differentiation, such that the neuron’s firing rate is a fractional derivative of slowly varying stimulus parameters. Biophysically, even though neuronal fractional differentiation effectively yields adaptation with many time scales, we find that its implementation requires only a few, properly balanced known adaptive mechanisms. Fractional differentiation provides single neurons with a fundamental and general computation that can contribute to efficient information processing, stimulus anticipation, and frequency independent phase shifts of oscillatory neuronal firing. PMID:18931665

  19. Targeting neurons and photons for optogenetics.

    PubMed

    Packer, Adam M; Roska, Botond; Häusser, Michael

    2013-07-01

    Optogenetic approaches promise to revolutionize neuroscience by using light to manipulate neural activity in genetically or functionally defined neurons with millisecond precision. Harnessing the full potential of optogenetic tools, however, requires light to be targeted to the right neurons at the right time. Here we discuss some barriers and potential solutions to this problem. We review methods for targeting the expression of light-activatable molecules to specific cell types, under genetic, viral or activity-dependent control. Next we explore new ways to target light to individual neurons to allow their precise activation and inactivation. These techniques provide a precision in the temporal and spatial activation of neurons that was not achievable in previous experiments. In combination with simultaneous recording and imaging techniques, these strategies will allow us to mimic the natural activity patterns of neurons in vivo, enabling previously impossible 'dream experiments'.

  20. Exertional heat stroke, rhabdomyolysis and susceptibility to malignant hyperthermia.

    PubMed

    Thomas, J; Crowhurst, T

    2013-09-01

    Unexpectedly severe exertional heat stroke and rhabdomyolysis should prompt a clinician to look for susceptibility to malignant hyperthermia. We report a case of exertional heat stroke and rhabdomyolysis in a man later determined to have the malignant hyperthermia phenotype. We review the existing literature regarding this association and suggest future research that could address areas of remaining clinical uncertainty. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  1. Aerobic Fitness and Risk of Ventricular Arrhythmia Following Physical Exertion.

    PubMed

    Chahal, Harpreet S; Mostofsky, Elizabeth; Mittleman, Murray A; Suskin, Neville; Speechley, Mark; Skanes, Allan C; Leong-Sit, Peter; Manlucu, Jaimie; Yee, Raymond; Klein, George J; Gula, Lorne J

    2016-04-01

    Brief episodes of physical exertion are associated with an immediately greater risk of cardiovascular events. Previous studies on the risk of ventricular arrhythmia (VA) shortly after exertion have not assessed if this risk differs according to the level of aerobic fitness or sedentary behaviour. Therefore, we conducted a prospective cohort study of patients with implantable cardioverter-defibrillators (ICDs) with a nested case-crossover analysis to examine the risk of VA shortly after exertion and whether this risk is modified by aerobic fitness and sedentary behaviour. Ninety-seven consecutive patients were recruited at the time of ICD implantation and 30 confirmed events occurred among patients who completed interviews about physical exertion preceding ICD therapy. We compared the frequency of exertion within an hour of ICD discharge to each patient's usual frequency of exertion reported at the time of ICD implantation. Within an hour of episodes of exertion, the risk of VA was 5.3 (95% confidence interval [CI], 2.7-10.6) times greater compared with periods of rest. The association was higher among patients with aerobic fitness below the median (relative risk [RR] = 17.5; 95% CI, 5.2-58.5) than for patients with aerobic fitness above the median (RR, 1.2; 95% CI, 0.4-4.2; P homogeneity = 0.002) and higher among patients who were sedentary (RR, 52.8; 95% CI, 10.1-277) compared with individuals who were not sedentary (RR, 3.2; 95% CI, 1.3-7.6; P homogeneity = 0.0002). Within 1 hour of episodes of exertion, there is an increased risk of VA, especially among individuals with lower levels of aerobic fitness and with sedentary behaviour. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  2. Glutamate Mediated Astrocytic Filtering of Neuronal Activity

    PubMed Central

    Herzog, Nitzan; De Pittà, Maurizio; Jacob, Eshel Ben; Berry, Hugues; Hanein, Yael

    2014-01-01

    Neuron-astrocyte communication is an important regulatory mechanism in various brain functions but its complexity and role are yet to be fully understood. In particular, the temporal pattern of astrocyte response to neuronal firing has not been fully characterized. Here, we used neuron-astrocyte cultures on multi-electrode arrays coupled to Ca2+ imaging and explored the range of neuronal stimulation frequencies while keeping constant the amount of stimulation. Our results reveal that astrocytes specifically respond to the frequency of neuronal stimulation by intracellular Ca2+ transients, with a clear onset of astrocytic activation at neuron firing rates around 3-5 Hz. The cell-to-cell heterogeneity of the astrocyte Ca2+ response was however large and increasing with stimulation frequency. Astrocytic activation by neurons was abolished with antagonists of type I metabotropic glutamate receptor, validating the glutamate-dependence of this neuron-to-astrocyte pathway. Using a realistic biophysical model of glutamate-based intracellular calcium signaling in astrocytes, we suggest that the stepwise response is due to the supralinear dynamics of intracellular IP3 and that the heterogeneity of the responses may be due to the heterogeneity of the astrocyte-to-astrocyte couplings via gap junction channels. Therefore our results present astrocyte intracellular Ca2+ activity as a nonlinear integrator of glutamate-dependent neuronal activity. PMID:25521344

  3. Do placebo expectations influence perceived exertion during physical exercise?

    PubMed

    Mothes, Hendrik; Leukel, Christian; Seelig, Harald; Fuchs, Reinhard

    2017-01-01

    This study investigates the role of placebo expectations in individuals' perception of exertion during acute physical exercise. Building upon findings from placebo and marketing research, we examined how perceived exertion is affected by expectations regarding a) the effects of exercise and b) the effects of the exercise product worn during the exercise. We also investigated whether these effects are moderated by physical self-concept. Seventy-eight participants conducted a moderate 30 min cycling exercise on an ergometer, with perceived exertion (RPE) measured every 5 minutes. Beforehand, each participant was randomly assigned to 1 of 4 conditions and watched a corresponding film clip presenting "scientific evidence" that the exercise would or would not result in health benefits and that the exercise product they were wearing (compression garment) would additionally enhance exercise benefits or would only be worn for control purposes. Participants' physical self-concept was assessed via questionnaire. Results partially demonstrated that participants with more positive expectations experienced reduced perceived exertion during the exercise. Furthermore, our results indicate a moderator effect of physical self-concept: Individuals with a high physical self-concept benefited (in terms of reduced perceived exertion levels) in particular from an induction of generally positive expectations. In contrast, individuals with a low physical self-concept benefited when positive expectations were related to the exercise product they were wearing. In sum, these results suggest that placebo expectations may be a further, previously neglected class of psychological factors that influence the perception of exertion.

  4. Musical agency reduces perceived exertion during strenuous physical performance.

    PubMed

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-10-29

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting.

  5. Musical agency reduces perceived exertion during strenuous physical performance

    PubMed Central

    Fritz, Thomas Hans; Hardikar, Samyogita; Demoucron, Matthias; Niessen, Margot; Demey, Michiel; Giot, Olivier; Li, Yongming; Haynes, John-Dylan; Villringer, Arno; Leman, Marc

    2013-01-01

    Music is known to be capable of reducing perceived exertion during strenuous physical activity. The current interpretation of this modulating effect of music is that music may be perceived as a diversion from unpleasant proprioceptive sensations that go along with exhaustion. Here we investigated the effects of music on perceived exertion during a physically strenuous task, varying musical agency, a task that relies on the experience of body proprioception, rather than simply diverting from it. For this we measured psychologically indicated exertion during physical workout with and without musical agency while simultaneously acquiring metabolic values with spirometry. Results showed that musical agency significantly decreased perceived exertion during workout, indicating that musical agency may actually facilitate physically strenuous activities. This indicates that the positive effect of music on perceived exertion cannot always be explained by an effect of diversion from proprioceptive feedback. Furthermore, this finding suggests that the down-modulating effect of musical agency on perceived exertion may be a previously unacknowledged driving force for the development of music in humans: making music makes strenuous physical activities less exhausting. PMID:24127588

  6. Astrocyte calcium signalling orchestrates neuronal synchronization in organotypic hippocampal slices

    PubMed Central

    Sasaki, Takuya; Ishikawa, Tomoe; Abe, Reimi; Nakayama, Ryota; Asada, Akiko; Matsuki, Norio; Ikegaya, Yuji

    2014-01-01

    Astrocytes are thought to detect neuronal activity in the form of intracellular calcium elevations; thereby, astrocytes can regulate neuronal excitability and synaptic transmission. Little is known, however, about how the astrocyte calcium signal regulates the activity of neuronal populations. In this study, we addressed this issue using functional multineuron calcium imaging in hippocampal slice cultures. Under normal conditions, CA3 neuronal networks exhibited temporally correlated activity patterns, occasionally generating large synchronization among a subset of cells. The synchronized neuronal activity was correlated with astrocyte calcium events. Calcium buffering by an intracellular injection of a calcium chelator into multiple astrocytes reduced the synaptic strength of unitary transmission between pairs of surrounding pyramidal cells and caused desynchronization of the neuronal networks. Uncaging the calcium in the astrocytes increased the frequency of neuronal synchronization. These data suggest an essential role of the astrocyte calcium signal in the maintenance of basal neuronal function at the circuit level. PMID:24710057

  7. Neuronal Ensemble Synchrony during Human Focal Seizures

    PubMed Central

    Ahmed, Omar J.; Harrison, Matthew T.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.

    2014-01-01

    Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (∼40–60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ∼3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50–100 ms level. In addition, transient fine synchrony occurred primarily during the initial ∼20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (∼80 Hz) gamma-band and during high-frequency oscillations (∼130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons. PMID:25057195

  8. Hippocampal neurons in schizophrenia

    PubMed Central

    Heckers, S.; Konradi, C.

    2014-01-01

    Summary The hippocampus is crucial for normal brain function, especially for the encoding and retrieval of multimodal sensory information. Neuropsychiatric disorders such as temporal lobe epilepsy, amnesia, and the dementias are associated with structural and functional abnormalities of specific hippocampal neurons. More recently we have also found evidence for a role of the hippocampus in the pathophysiology of schizophrenia. The most consistent finding is a subtle, yet significant volume difference in schizophrenia. Here we review the cellular and molecular basis of smaller hippocampal volume in schizophrenia. In contrast to neurodegenerative disorders, total hippocampal cell number is not markedly decreased in schizophrenia. However, the intriguing finding of a selective loss of hippocampal inter-neurons deserves further study. Two neurotransmitter receptors, the GABAA and AMPA/kainate glutamate receptors, appear to be abnormal, whereas changes of the NMDA glutamate receptor are less robust. The expression of several genes, including those related to the GABAergic system, neurodevelopment, and synaptic function, is decreased in schizophrenia. Taken together, recent studies of hippocampal cell number, protein expression, and gene regulation point towards an abnormality of hippocampal architecture in schizophrenia. PMID:12111476

  9. Genetic dissection of midbrain dopamine neuron development in vivo.

    PubMed

    Ellisor, Debra; Rieser, Caroline; Voelcker, Bettina; Machan, Jason T; Zervas, Mark

    2012-12-15

    Midbrain dopamine (MbDA) neurons are partitioned into medial and lateral cohorts that control complex functions. However, the genetic underpinnings of MbDA neuron heterogeneity are unclear. While it is known that Wnt1-expressing progenitors contribute to MbDA neurons, the role of Wnt1 in MbDA neuron development in vivo is unresolved. We show that mice with a spontaneous point mutation in Wnt1 have a unique phenotype characterized by the loss of medial MbDA neurons concomitant with a severe depletion of Wnt1-expressing progenitors and diminished LMX1a-expressing progenitors. Wnt1 mutant embryos also have alterations in a hierarchical gene regulatory loop suggesting multiple gene involvement in the Wnt1 mutant MbDA neuron phenotype. To investigate this possibility, we conditionally deleted Gbx2, Fgf8, and En1/2 after their early role in patterning and asked whether these genetic manipulations phenocopied the depletion of MbDA neurons in Wnt1 mutants. The conditional deletion of Gbx2 did not result in re-positioning or distribution of MbDA neurons. The temporal deletion of Fgf8 did not result in the loss of either LMX1a-expressing progenitors nor the initial population of differentiated MbDA neurons, but did result in a complete loss of MbDA neurons at later stages. The temporal deletion and species specific manipulation of En1/2 demonstrated a continued and species specific role of Engrailed genes in MbDA neuron development. Notably, our conditional deletion experiments revealed phenotypes dissimilar to Wnt1 mutants indicating the unique role of Wnt1 in MbDA neuron development. By placing Wnt1, Fgf8, and En1/2 in the context of their temporal requirement for MbDA neuron development, we further deciphered the developmental program underpinning MbDA neuron progenitors.

  10. Prospective Coding by Spiking Neurons

    PubMed Central

    Brea, Johanni; Gaál, Alexisz Tamás; Senn, Walter

    2016-01-01

    Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron’s firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ). PMID:27341100

  11. Genetic manipulation of single neurons in vivo reveals specific roles of flamingo in neuronal morphogenesis.

    PubMed

    Sweeney, Neal T; Li, Wenjun; Gao, Fen-Biao

    2002-07-01

    To study the roles of intracellular factors in neuronal morphogenesis, we used the mosaic analysis with a repressible cell marker (MARCM) technique to visualize identifiable single multiple dendritic (MD) neurons in living Drosophila larvae. We found that individual neurons in the peripheral nervous system (PNS) developed clear morphological polarity and diverse dendritic branching patterns in larval stages. Each MD neuron in the same dorsal cluster developed a unique dendritic field, suggesting that they have specific physiological functions. Single-neuron analysis revealed that Flamingo did not affect the general dendritic branching patterns in postmitotic neurons. Instead, Flamingo limited the extension of one or more dorsal dendrites without grossly affecting lateral branches. The dendritic overextension phenotype was partially conferred by the precocious initiation of dorsal dendrites in flamingo mutant embryos. In addition, Flamingo is required cell autonomously to promote axonal growth and to prevent premature axonal branching of PNS neurons. Our molecular analysis also indicated that the amino acid sequence near the first EGF motif is important for the proper localization and function of Flamingo. These results demonstrate that Flamingo plays a role in early neuronal differentiation and exerts specific effects on dendrites and axons.

  12. High-Degree Neurons Feed Cortical Computations.

    PubMed

    Timme, Nicholas M; Ito, Shinya; Myroshnychenko, Maxym; Nigam, Sunny; Shimono, Masanori; Yeh, Fang-Chin; Hottowy, Pawel; Litke, Alan M; Beggs, John M

    2016-05-01

    Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree) or sends out (out-degree). To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series) and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts) to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to which a neuron

  13. High-Degree Neurons Feed Cortical Computations

    PubMed Central

    Timme, Nicholas M.; Ito, Shinya; Shimono, Masanori; Yeh, Fang-Chin; Litke, Alan M.; Beggs, John M.

    2016-01-01

    Recent work has shown that functional connectivity among cortical neurons is highly varied, with a small percentage of neurons having many more connections than others. Also, recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive. Therefore, it is now possible to investigate how information modification, or computation, depends on the number of connections a neuron receives (in-degree) or sends out (out-degree). To do this, we recorded the simultaneous spiking activity of hundreds of neurons in cortico-hippocampal slice cultures using a high-density 512-electrode array. This preparation and recording method combination produced large numbers of neurons recorded at temporal and spatial resolutions that are not currently available in any in vivo recording system. We utilized transfer entropy (a well-established method for detecting linear and nonlinear interactions in time series) and the partial information decomposition (a powerful, recently developed tool for dissecting multivariate information processing into distinct parts) to quantify computation between neurons where information flows converged. We found that computations did not occur equally in all neurons throughout the networks. Surprisingly, neurons that computed large amounts of information tended to receive connections from high out-degree neurons. However, the in-degree of a neuron was not related to the amount of information it computed. To gain insight into these findings, we developed a simple feedforward network model. We found that a degree-modified Hebbian wiring rule best reproduced the pattern of computation and degree correlation results seen in the real data. Interestingly, this rule also maximized signal propagation in the presence of network-wide correlations, suggesting a mechanism by which cortex could deal with common random background input. These are the first results to show that the extent to which a neuron

  14. Challenging Return to Play Decisions: Heat Stroke, Exertional Rhabdomyolysis, and Exertional Collapse Associated With Sickle Cell Trait.

    PubMed

    Asplund, Chad A; O'Connor, Francis G

    2016-01-01

    Sports medicine providers frequently return athletes to play after sports-related injuries and conditions. Many of these conditions have guidelines or medical evidence to guide the decision-making process. Occasionally, however, sports medicine providers are challenged with complex medical conditions for which there is little evidence-based guidance and physicians are instructed to individualize treatment; included in this group of conditions are exertional heat stroke (EHS), exertional rhabdomyolysis (ER), and exertional collapse associated with sickle cell trait (ECAST). The MEDLINE (2000-2015) database was searched using the following search terms: exertional heat stroke, exertional rhabdomyolysis, and exertional collapse associated with sickle cell trait. References from consensus statements, review articles, and book chapters were also utilized. Clinical review. Level 4. These entities are unique in that they may cause organ system damage capable of leading to short- or long-term detriments to physical activity and may not lend to complete recovery, potentially putting the athlete at risk with premature return to play. With a better understanding of the pathophysiology of EHS, ER, and ECAST and the factors associated with recovery, better decisions regarding return to play may be made. © 2015 The Author(s).

  15. Neuronal uptake of serum albumin is associated with neuron damage during the development of epilepsy

    PubMed Central

    Liu, Zanhua; Liu, Jinjie; Wang, Suping; Liu, Sibo; Zhao, Yongbo

    2016-01-01

    It is well established that brain blood barrier dysfunction following the onset of seizures may lead to serum albumin extravasation into the brain. However, the effect of albumin extravasation on the development of epilepsy is yet to be fully elucidated. Previous studies have predominantly focused on the effect of albumin absorption by astrocytes; however, the present study investigated the effects of neuronal uptake of albumin in vitro and in kainic acid-induced Sprague-Dawley rat models of temporal lobe epilepsy. In the present study, electroencephalogram recordings were conducted to record seizure onset, Nissl and Evans blue staining were used to detect neuronal damage and albumin extravasation, respectively, and double immunofluorescence was used to explore neuronal absorption of albumin. Cell counting was also conducted in vitro to determine whether albumin contributes to neuronal death. The results of the present study indicated that extravasated serum albumin was absorbed by neurons, and the neurons that had absorbed albumin died and were dissolved 28 days after seizure onset in vivo. Furthermore, significant neuronal death was detected after albumin absorption in vitro in a dose- and time-dependent manner. These results suggested that albumin may be absorbed by neurons following the onset of seizures. Furthermore, the results indicated that neuronal albumin uptake may be associated with neuronal damage and death in epileptic seizures. Therefore, attenuating albumin extravasation following epileptic seizures may reduce brain damage and slow the development of epilepsy. PMID:27446263

  16. Analysis of stimuli triggering attacks of paroxysmal dystonia induced by exertion

    PubMed Central

    Meyer, B; Irlbacher, K; Meierkord, H

    2001-01-01

    In a patient with a familial form of paroxysmal exertion induced dyskinesia (PED), the efficacy of different stimuli and manoeuvres in triggering dystonic attacks in the arm was studied. As a new approach, transcranial magnetic stimulation (TMS) of the motor cortex was used to trigger motor paroxysms and to monitor cortical excitability during attacks. Motor paroxysms could be provoked by muscle vibration, passive movements, TMS, magnetic stimulation of the brachial plexus, and electrical nerve stimulation. Sham stimulation over the motor cortex and thermal and tactile cutaneous stimuli were ineffective in triggering attacks. It is concluded that dystonic attacks are triggered by proprioceptive afferents rather than cutaneous stimuli or the descending motor command itself. Outside the attacks, motor cortical excitatory and inhibitory neuronal mechanisms as assessed by TMS (response threshold and amplitudes, duration of the contralateral and ipsilateral silent period, corticocortical inhibition, and facilitation) were normal, which underlines the paroxysmal character of the disorder.

 PMID:11160479

  17. Cyclic AMP imaging sheds light on PDF signaling in circadian clock neurons.

    PubMed

    Tomchik, Seth M; Davis, Ronald L

    2008-04-24

    In Drosophila, the neuropeptide PDF is required for circadian rhythmicity, but it is unclear where PDF acts. In this issue of Neuron, Shafer et al. use a novel bioimaging methodology to demonstrate that PDF elevates cAMP in nearly all clock neurons. Thus, PDF apparently exerts more widespread effects on the circadian clock network than suggested by previous studies of PDF receptor expression.

  18. Drosophila intermediate neural progenitors produce lineage-dependent related series of diverse neurons

    PubMed Central

    Wang, Yu-Chun; Yang, Jacob S.; Johnston, Rebecca; Ren, Qingzhong; Lee, Ying-Jou; Luan, Haojiang; Brody, Thomas; Odenwald, Ward F.; Lee, Tzumin

    2014-01-01

    Drosophila type II neuroblasts (NBs), like mammalian neural stem cells, deposit neurons through intermediate neural progenitors (INPs) that can each produce a series of neurons. Both type II NBs and INPs exhibit age-dependent expression of various transcription factors, potentially specifying an array of diverse neurons by combinatorial temporal patterning. Not knowing which mature neurons are made by specific INPs, however, conceals the actual variety of neuron types and limits further molecular studies. Here we mapped neurons derived from specific type II NB lineages and found that sibling INPs produced a morphologically similar but temporally regulated series of distinct neuron types. This suggests a common fate diversification program operating within each INP that is modulated by NB age to generate slightly different sets of diverse neurons based on the INP birth order. Analogous mechanisms might underlie the expansion of neuron diversity via INPs in mammalian brain. PMID:24306106

  19. Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

    PubMed Central

    Scalco, Renata S; Snoeck, Marc; Quinlivan, Ros; Treves, Susan; Laforét, Pascal; Jungbluth, Heinz; Voermans, Nicol C

    2016-01-01

    Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine kinase (CK) levels with or without associated myoglobinuria. Mild cases may remain unnoticed or undiagnosed. Exertional rhabdomyolysis is well described among athletes and military personnel, but may occur in anybody exposed to unaccustomed exercise. In contrast, exertional rhabdomyolysis may be the first manifestation of a genetic muscle disease that lowers the exercise threshold for developing muscle breakdown. Repeated episodes of exertional rhabdomyolysis should raise the suspicion of such an underlying disorder, in particular in individuals in whom the severity of the rhabdomyolysis episodes exceeds the expected response to the exercise performed. The present review aims to provide a practical guideline for the acute management and postepisode counselling of patients with exertional rhabdomyolysis, with a particular emphasis on when to suspect an underlying genetic disorder. The pathophysiology and its clinical features are reviewed, emphasising four main stepwise approaches: (1) the clinical significance of an acute episode, (2) risks of renal impairment, (3) clinical indicators of an underlying genetic disorders and (4) when and how to recommence sport activity following an acute episode of rhabdomyolysis. Genetic backgrounds that appear to be associated with both enhanced athletic performance and increased rhabdomyolysis risk are briefly reviewed. PMID:27900193

  20. Neuronal loss as evidenced by automated quantification of neuronal density following moderate and severe traumatic brain injury in rats.

    PubMed

    Balança, Baptiste; Bapteste, Lionel; Lieutaud, Thomas; Ressnikoff, Denis; Guy, Rainui; Bezin, Laurent; Marinesco, Stéphane

    2016-01-01

    Traumatic brain injury causes widespread neurological lesions that can be reproduced in animals with the lateral fluid percussion (LFP) model. The characterization of the pattern of neuronal death generated in this model remains unclear, involving both cortical and subcortical brain regions. Here, 7 days after moderate (3 atmospheres absolute [ATA]) or severe (3.8 ATA) LFP, we estimated neuronal loss by using immunohistochemistry together with a computer-assisted automated method for quantifying neuronal density in brain sections. Neuronal counts were performed ipsilateral to the impact, in the parietal cortex ventral to the site of percussion, in the temporal cortex, in the dorsal thalamus, and in the hippocampus. These results were compared with the counts observed at similar areas in sham animals. We found that neuronal density was severely decreased in the temporal cortex (-60%), in the dorsal thalamus (-63%), and in area CA3 of the hippocampus (-36%) of injured animals compared with controls but was not significantly modified in the cortices located immediately ventral to the impact. Total cellular density increased in brain structures displaying neuronal death, suggesting the presence of gliosis. The increase in the severity of LFP did not change the pattern of neuronal injury. This automated method simplified the study of neuronal loss following traumatic brain injury and allowed the identification of a pattern of neuronal loss that spreads from the dorsal thalamus to the temporal cortex, with the most severe lesions being in brain structures remote from the site of impact.

  1. Preventing NAD+ Depletion Protects Neurons against Excitotoxicity

    PubMed Central

    Liu, Dong; Pitta, Michael; Mattson, Mark P.

    2008-01-01

    Neurons are excitable cells that require large amounts of energy to support their survival and functions and are therefore prone to excitotoxicity, which involves energy depletion. By examining bioenergetic changes induced by glutamate, we found that the cellular nicotinamide adenine dinucleotide (NAD+) level is a critical determinant of neuronal survival. The bioenergetic effects of mitochondrial uncoupling and caloric restriction were also examined in cultured neurons and rodent brain. 2, 4-dinitrophenol (DNP) is a chemical mitochondrial uncoupler that stimulates glucose uptake and oxygen consumption on cultured neurons, which accelerates oxidation of NAD(P)H to NAD+ in mitochondria. The NAD+-dependent histone deacetylase sirtulin 1 (SIRT1) and glucose transporter 1 (GLUT1) mRNA are upregulated mouse brain under caloric restriction. To examine whether NAD+ mediates neuroprotective effects, nicotinamide, a precursor of NAD+ and inhibitor of SIRT1 and poly (ADP-ribose) polymerase 1 (PARP1) (two NAD+-dependent enzymes), was employed. Nicotinamide attenuated excitotoxic death and preserved cellular NAD+ levels to support SIRT1 and PARP 1 activities. Our findings suggest that mild mitochondrial uncoupling and caloric restriction exert hormetic effects by stimulating bioenergetics in neurons thereby increasing tolerance of neurons to metabolic stress. PMID:19076449

  2. A case of mitochondrial cytopathy with exertion induced dystonia

    PubMed Central

    Chandra, Sadanandavalli Retnaswami; Issac, Thomas Gregor

    2015-01-01

    Paroxysmal dystonias are a group of relatively benign hyperkinetic childhood movement disorders of varied etiology. Mitochondrial diseases are well known to produce persistent dystonias as sequelae, but paroxysmal exertion induced dystonia has been reported in only one case to the best of our knowledge. Two siblings born to consanguineous parents presented with early-onset exertion induced dystonia, which was unresponsive to diphenylhydantoin and carbamazepine. A trial with valproate in one of the siblings turned fatal within 24 h. Based on this clue, the second child was investigated and found to suffer from complex I deficiency with a paternally inherited dominant nuclear DNA mutation, which is responsive to the mitochondrial cocktail. Exertion induced dystonia can be a rare manifestation of complex I deficiency. PMID:26557169

  3. The role of exercise in the etiology of exertional heatstroke.

    PubMed

    Hubbard, R W

    1990-02-01

    Exertional heatstroke usually occurs among healthy, fit individuals who are motivated to perform strenuous exercise because of peer pressure, discipline, or athletic competition. In fact, exertional heatstroke deaths among high school athletes in the United States (ranked third only to head and neck injuries and heart failures), and the reluctance of race directors to cancel or postpone mass participation road races during periods of severe heat and humidity, emphasize a continuing need for widespread dissemination of information. The purposes of this symposium are 1) to convey essential information to the members of ACSM who are involved in exercise prescription, patient care, or athletic training; and 2) to disseminate recent scientific theories and research concerning exertional heatstroke.

  4. Microsurgical Anatomy of the Temporal Lobe and Its Implications on Temporal Lobe Epilepsy Surgery

    PubMed Central

    Kucukyuruk, Baris; Richardson, R. Mark; Wen, Hung Tzu; Fernandez-Miranda, Juan Carlos; Rhoton, Albert L.

    2012-01-01

    Objective. We review the neuroanatomical aspects of the temporal lobe related to the temporal lobe epilepsy. The neuronal, the ventricular, and the vascular structures are demonstrated. Methods. The previous articles published from the laboratory of the senior author are reviewed. Results. The temporal lobe has four surfaces. The medial surface has a complicated microanatomy showing close relation to the intraventricular structures, such as the amygdala or the hippocampus. There are many white matter bundles in the temporal lobe showing relation to the extra- and intraventricular structures. The surgical approaches commonly performed to treat temporal lobe epilepsy are discussed under the light of these data. Conclusion. A thorough knowledge of the microanatomy is necessary in cortical, subcortical, and intraventricular structures of the temporal lobe to achieve better results. PMID:22957242

  5. [Are we all on the same temporal page? The moderating effects of temporal team cognition on the polychronicity diversity–team performance relationship].

    PubMed

    Mohammed, Susan; Nadkarni, Sucheta

    2014-05-01

    Integrating research on polychronicity, team diversity, and team cognition, we hypothesized that shared temporal cognition (overlapping knowledge) and temporal transactive memory systems (differentiated knowledge) would moderate the effects of polychronicity diversity on team performance. Results from 71 teams in an Indian organization revealed opposing moderating effects in that shared temporal cognition attenuated, but temporal transactive memory systems amplified, the negative effects of polychronicity diversity on team performance. Shared temporal cognition also exerted a strong, positive effect on team performance. Study results provide support for the continued examination of polychronicity diversity and temporal team cognition. (c) 2014 APA, all rights reserved.

  6. Adaptation to speed in macaque middle temporal and medial superior temporal areas.

    PubMed

    Price, Nicholas S C; Born, Richard T

    2013-03-06

    The response of a sensory neuron to an unchanging stimulus typically adapts, showing decreases in response gain that are accompanied by changes in the shape of tuning curves. It remains unclear whether these changes arise purely due to spike rate adaptation within single neurons or whether they are dependent on network interactions between neurons. Further, it is unclear how the timescales of neural and perceptual adaptation are related. To examine this issue, we compared speed tuning of middle temporal (MT) and medial superior temporal neurons in macaque visual cortex after adaptation to two different reference speeds. For 75% of speed-tuned units, adaptation caused significant changes in tuning that could be explained equally well as lateral shifts, vertical gain changes, or both. These tuning changes occurred rapidly, as both neuronal firing rate and Fano factor showed no evidence of changing beyond the first 500 ms after motion onset, and the magnitude of tuning curve changes showed no difference between trials with adaptation durations shorter or longer than 1 s. Importantly, the magnitude of tuning shifts was correlated with the transient-sustained index, which measures a well characterized form of rapid response adaptation in MT, and is likely associated with changes at the level of neuronal networks. Tuning curves changed in a manner that increased neuronal sensitivity around the adapting speed, consistent with improvements in human and macaque psychophysical performance that we observed over the first several hundred ms of adaptation.

  7. A Technique for Establishing True Levels of Muscle Strength Exertion

    DTIC Science & Technology

    1980-01-01

    performed -"aximal or submaximal isometric strength exertions. The exertions tested were elbow flexion, finger flexion, knee flexion and knee...190.1 167.11 17.3350 Buttock-Knee Length (cm) 54.1 66.7 59.29 3.2106 Knee Height, sitting (cm) 46.5 58.7 52.91 2.8737 Shoulder- Elbow Length (cm) 29.3...propped the elbow of the right arm on the arm rest, extended the fore- arm directly forward so that the cuff was exactly above the load cell, with

  8. Temporal pattern processing in songbirds.

    PubMed

    Comins, Jordan A; Gentner, Timothy Q

    2014-10-01

    Understanding how the brain perceives, organizes and uses patterned information is directly related to the neurobiology of language. Given the present limitations, such knowledge at the scale of neurons, neural circuits and neural populations can only come from non-human models, focusing on shared capacities that are relevant to language processing. Here we review recent advances in the behavioral and neural basis of temporal pattern processing of natural auditory communication signals in songbirds, focusing on European starlings. We suggest a general inhibitory circuit for contextual modulation that can act to control sensory representations based on patterning rules.

  9. Oscillatory integration windows in neurons

    PubMed Central

    Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark

    2016-01-01

    Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking. PMID:27976720

  10. Oscillatory integration windows in neurons.

    PubMed

    Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark

    2016-12-15

    Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking.

  11. The neuronal code(s) of the cerebellum.

    PubMed

    Heck, Detlef H; De Zeeuw, Chris I; Jaeger, Dieter; Khodakhah, Kamran; Person, Abigail L

    2013-11-06

    Understanding how neurons encode information in sequences of action potentials is of fundamental importance to neuroscience. The cerebellum is widely recognized for its involvement in the coordination of movements, which requires muscle activation patterns to be controlled with millisecond precision. Understanding how cerebellar neurons accomplish such high temporal precision is critical to understanding cerebellar function. Inhibitory Purkinje cells, the only output neurons of the cerebellar cortex, and their postsynaptic target neurons in the cerebellar nuclei, fire action potentials at high, sustained frequencies, suggesting spike rate modulation as a possible code. Yet, millisecond precise spatiotemporal spike activity patterns in Purkinje cells and inferior olivary neurons have also been observed. These results and ongoing studies suggest that the neuronal code used by cerebellar neurons may span a wide time scale from millisecond precision to slow rate modulations, likely depending on the behavioral context.

  12. High-throughput imaging of neuronal activity in Caenorhabditis elegans

    PubMed Central

    Larsch, Johannes; Ventimiglia, Donovan; Bargmann, Cornelia I.; Albrecht, Dirk R.

    2013-01-01

    Neuronal responses to sensory inputs can vary based on genotype, development, experience, or stochastic factors. Existing neuronal recording techniques examine a single animal at a time, limiting understanding of the variability and range of potential responses. To scale up neuronal recordings, we here describe a system for simultaneous wide-field imaging of neuronal calcium activity from at least 20 Caenorhabditis elegans animals under precise microfluidic chemical stimulation. This increased experimental throughput was used to perform a systematic characterization of chemosensory neuron responses to multiple odors, odor concentrations, and temporal patterns, as well as responses to pharmacological manipulation. The system allowed recordings from sensory neurons and interneurons in freely moving animals, whose neuronal responses could be correlated with behavior. Wide-field imaging provides a tool for comprehensive circuit analysis with elevated throughput in C. elegans. PMID:24145415

  13. Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state.

    PubMed

    Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar

    2015-07-07

    Spontaneous fluctuations in neuronal activity emerge at many spatial and temporal scales in cortex. Population measures found these fluctuations to organize as scale-invariant neuronal avalanches, suggesting cortical dynamics to be critical. Macroscopic dynamics, though, depend on physiological states and are ambiguous as to their cellular composition, spatiotemporal origin, and contributions from synaptic input or action potential (AP) output. Here, we study spontaneous firing in pyramidal neurons (PNs) from rat superficial cortical layers in vivo and in vitro using 2-photon imaging. As the animal transitions from the anesthetized to awake state, spontaneous single neuron firing increases in irregularity and assembles into scale-invariant avalanches at the group level. In vitro spike avalanches emerged naturally yet required balanced excitation and inhibition. This demonstrates that neuronal avalanches are linked to the global physiological state of wakefulness and that cortical resting activity organizes as avalanches from firing of local PN groups to global population activity.

  14. Ceftriaxone Blocks the Polymerization of α-Synuclein and Exerts Neuroprotective Effects in Vitro

    PubMed Central

    2013-01-01

    The β-lactam antibiotic ceftriaxone was suggested as a therapeutic agent in several neurodegenerative disorders, either for its ability to counteract glutamate-mediated toxicity, as in cerebral ischemia, or for its ability to enhance the degradation of misfolded proteins, as in Alexander’s disease. Recently, the efficacy of ceftriaxone in neuroprotection of dopaminergic neurons in a rat model of Parkinson’s disease was documented. However, which characteristics of ceftriaxone mediate its therapeutic effects remains unclear. Since, at the molecular level, neuronal α-synuclein inclusions and pathological α-synuclein transmission play a leading role in initiation of Parkinson-like neurodegeneration, we thought of investigating, by circular dichroism spectroscopy, the capability of ceftriaxone to interact with α-synuclein. We found that ceftriaxone binds with good affinity to α-synuclein and blocks its in vitro polymerization. Considering this finding, we also documented that ceftriaxone exerts neuroprotective action in an in vitro model of Parkinson’s disease. Our data, in addition to the findings on neuroprotective activity of ceftriaxone on Parkinson-like neurodegeneration in vivo, indicates ceftriaxone as a potential agent in treatment of Parkinson’s disease. PMID:24099687

  15. Distinct mechanisms for coding of visual actions in macaque temporal cortex.

    PubMed

    Vangeneugden, Joris; De Mazière, Patrick A; Van Hulle, Marc M; Jaeggli, Tobias; Van Gool, Luc; Vogels, Rufin

    2011-01-12

    Temporal cortical neurons are known to respond to visual dynamic-action displays. Many human psychophysical and functional imaging studies examining biological motion perception have used treadmill walking, in contrast to previous macaque single-cell studies. We assessed the coding of locomotion in rhesus monkey (Macaca mulatta) temporal cortex using movies of stationary walkers, varying both form and motion (i.e., different facing directions) or varying only the frame sequence (i.e., forward vs backward walking). The majority of superior temporal sulcus and inferior temporal neurons were selective for facing direction, whereas a minority distinguished forward from backward walking. Support vector machines using the temporal cortical population responses as input classified facing direction well, but forward and backward walking less so. Classification performance for the latter improved markedly when the within-action response modulation was considered, reflecting differences in momentary body poses within the locomotion sequences. Responses to static pose presentations predicted the responses during the course of the action. Analyses of the responses to walking sequences wherein the start frame was varied across trials showed that some neurons also carried a snapshot sequence signal. Such sequence information was present in neurons that responded to static snapshot presentations and in neurons that required motion. Our data suggest that actions are analyzed by temporal cortical neurons using distinct mechanisms. Most neurons predominantly signal momentary pose. In addition, temporal cortical neurons, including those responding to static pose, are sensitive to pose sequence, which can contribute to the signaling of learned action sequences.

  16. Pre-semantically defined temporal windows for cognitive processing

    PubMed Central

    Pöppel, Ernst

    2009-01-01

    Neuronal oscillations of different frequencies are hypothesized to be basic for temporal perception; this theoretical concept provides the frame to discuss two temporal mechanisms that are thought to be essential for cognitive processing. One such mechanism operates with periods of oscillations in the range of some tens of milliseconds, and is used for complexity reduction of temporally and spatially distributed neuronal activities. Experimental evidence comes from studies on temporal-order threshold, choice reaction time, single-cell activities, evoked responses in neuronal populations or latency distributions of oculomotor responses. The other mechanism refers to pre-semantic integration in the temporal range of approximately 2–3 s. Experimental evidence comes from studies on temporal reproduction, sensorimotor synchronization, intentional movements, speech segmentation, the shift rate of ambiguous stimuli in the visual or auditory modality or the temporal modulation of the mismatch negativity. These different observations indicate the existence of a universal process of temporal integration underlying the mental machinery. This process is believed to be basic for maintenance and change of perceptual identity. Owing to the omnipresence of this kind of temporal segmentation, it is suggested to use this process for a pragmatic definition of the states of being conscious or the ‘subjective presence’. PMID:19487191

  17. Temporal integration at consecutive processing stages in the auditory pathway of the grasshopper

    PubMed Central

    Ronacher, Bernhard

    2015-01-01

    Temporal integration in the auditory system of locusts was quantified by presenting single clicks and click pairs while performing intracellular recordings. Auditory neurons were studied at three processing stages, which form a feed-forward network in the metathoracic ganglion. Receptor neurons and most first-order interneurons (“local neurons”) encode the signal envelope, while second-order interneurons (“ascending neurons”) tend to extract more complex, behaviorally relevant sound features. In different neuron types of the auditory pathway we found three response types: no significant temporal integration (some ascending neurons), leaky energy integration (receptor neurons and some local neurons), and facilitatory processes (some local and ascending neurons). The receptor neurons integrated input over very short time windows (<2 ms). Temporal integration on longer time scales was found at subsequent processing stages, indicative of within-neuron computations and network activity. These different strategies, realized at separate processing stages and in parallel neuronal pathways within one processing stage, could enable the grasshopper's auditory system to evaluate longer time windows and thus to implement temporal filters, while at the same time maintaining a high temporal resolution. PMID:25609104

  18. Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons.

    PubMed

    Dergacheva, Olga; Yamanaka, Akihiro; Schwartz, Alan R; Polotsky, Vsevolod Y; Mendelowitz, David

    2017-04-01

    Orexin neurons, and activation of orexin receptors, are generally thought to be sympathoexcitatory; however, the functional connectivity between orexin neurons and a likely sympathetic target, the hypothalamic spinally projecting neurons (SPNs) in the paraventricular nucleus of the hypothalamus (PVN) has not been established. To test the hypothesis that orexin neurons project directly to SPNs in the PVN, channelrhodopsin-2 (ChR2) was selectively expressed in orexin neurons to enable photoactivation of ChR2-expressing fibers while examining evoked postsynaptic currents in SPNs in rat hypothalamic slices. Selective photoactivation of orexin fibers elicited short-latency postsynaptic currents in all SPNs tested (n = 34). These light-triggered responses were heterogeneous, with a majority being excitatory glutamatergic responses (59%) and a minority of inhibitory GABAergic (35%) and mixed glutamatergic and GABAergic currents (6%). Both glutamatergic and GABAergic responses were present in the presence of tetrodotoxin and 4-aminopyridine, suggesting a monosynaptic connection between orexin neurons and SPNs. In addition to generating postsynaptic responses, photostimulation facilitated action potential firing in SPNs (current clamp configuration). Glutamatergic, but not GABAergic, postsynaptic currents were diminished by application of the orexin receptor antagonist almorexant, indicating orexin release facilitates glutamatergic neurotransmission in this pathway. This work identifies a neuronal circuit by which orexin neurons likely exert sympathoexcitatory control of cardiovascular function.NEW & NOTEWORTHY This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not GABAergic

  19. Divergent Modulation of Nociception by Glutamatergic and GABAergic Neuronal Subpopulations in the Periaqueductal Gray

    PubMed Central

    Grajales-Reyes, Jose G.; Copits, Bryan A.; O’Brien, Daniel E.; Trigg, Sarah L.; Gomez, Adrian M.

    2017-01-01

    Abstract The ventrolateral periaqueductal gray (vlPAG) constitutes a major descending pain modulatory system and is a crucial site for opioid-induced analgesia. A number of previous studies have demonstrated that glutamate and GABA play critical opposing roles in nociceptive processing in the vlPAG. It has been suggested that glutamatergic neurotransmission exerts antinociceptive effects, whereas GABAergic neurotransmission exert pronociceptive effects on pain transmission, through descending pathways. The inability to exclusively manipulate subpopulations of neurons in the PAG has prevented direct testing of this hypothesis. Here, we demonstrate the different contributions of genetically defined glutamatergic and GABAergic vlPAG neurons in nociceptive processing by employing cell type-specific chemogenetic approaches in mice. Global chemogenetic manipulation of vlPAG neuronal activity suggests that vlPAG neural circuits exert tonic suppression of nociception, consistent with previous pharmacological and electrophysiological studies. However, selective modulation of GABAergic or glutamatergic neurons demonstrates an inverse regulation of nociceptive behaviors by these cell populations. Selective chemogenetic activation of glutamatergic neurons, or inhibition of GABAergic neurons, in vlPAG suppresses nociception. In contrast, inhibition of glutamatergic neurons, or activation of GABAergic neurons, in vlPAG facilitates nociception. Our findings provide direct experimental support for a model in which excitatory and inhibitory neurons in the PAG bidirectionally modulate nociception. PMID:28374016

  20. 20 CFR 416.969a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....969a Section 416.969a Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms of... assessment along with your age, education, and work experience to decide if you can adjust to any other...

  1. 20 CFR 404.1569a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....1569a Section 404.1569a Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms of... assessment along with your age, education, and work experience to decide if you can adjust to any other...

  2. Perception of Forces Exerted by Objects in Collision Events

    ERIC Educational Resources Information Center

    White, Peter A.

    2009-01-01

    Impressions of force are commonplace in the visual perception of objects interacting. It is proposed that these impressions have their source in haptically mediated experiences of exertion of force in actions on objects. Visual impressions of force in interactions between objects occur by a kind of generalization of the proprioceptive impression…

  3. 20 CFR 404.1569a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Exertional and nonexertional limitations. 404.1569a Section 404.1569a Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404...

  4. 20 CFR 404.1567 - Physical exertion requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Physical exertion requirements. 404.1567 Section 404.1567 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404.1567...

  5. 20 CFR 404.1569a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Exertional and nonexertional limitations. 404.1569a Section 404.1569a Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404...

  6. 20 CFR 404.1567 - Physical exertion requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Physical exertion requirements. 404.1567 Section 404.1567 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404.1567...

  7. 20 CFR 404.1567 - Physical exertion requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Physical exertion requirements. 404.1567 Section 404.1567 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404.1567...

  8. 20 CFR 404.1569a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Exertional and nonexertional limitations. 404.1569a Section 404.1569a Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404...

  9. 20 CFR 404.1567 - Physical exertion requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Physical exertion requirements. 404.1567 Section 404.1567 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404.1567...

  10. 20 CFR 404.1569a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Exertional and nonexertional limitations. 404.1569a Section 404.1569a Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining Disability and Blindness Vocational Considerations § 404...

  11. Perception of Forces Exerted by Objects in Collision Events

    ERIC Educational Resources Information Center

    White, Peter A.

    2009-01-01

    Impressions of force are commonplace in the visual perception of objects interacting. It is proposed that these impressions have their source in haptically mediated experiences of exertion of force in actions on objects. Visual impressions of force in interactions between objects occur by a kind of generalization of the proprioceptive impression…

  12. Exertional heat illness: emerging concepts and advances in prehospital care.

    PubMed

    Pryor, Riana R; Roth, Ronald N; Suyama, Joe; Hostler, David

    2015-06-01

    Exertional heat illness is a classification of disease with clinical presentations that are not always diagnosed easily. Exertional heat stroke is a significant cause of death in competitive sports, and the increasing popularity of marathons races and ultra-endurance competitions will make treating many heat illnesses more common for Emergency Medical Services (EMS) providers. Although evidence is available primarily from case series and healthy volunteer studies, the consensus for treating exertional heat illness, coupled with altered mental status, is whole body rapid cooling. Cold or ice water immersion remains the most effective treatment to achieve this goal. External thermometry is unreliable in the context of heat stress and direct internal temperature measurement by rectal or esophageal probes must be used when diagnosing heat illness and during cooling. With rapid recognition and implementation of effective cooling, most patients suffering from exertional heat stroke will recover quickly and can be discharged home with instructions to rest and to avoid heat stress and exercise for a minimum of 48 hours; although, further research pertaining to return to activity is warranted.

  13. Perceived Exertion: An Old Exercise Tool Finds New Applications.

    ERIC Educational Resources Information Center

    Monahan, Terry

    1988-01-01

    Perceived exertion scales, based on subjective perception of energy output, are gaining respect as prescribing and monitoring tools for individual exercise programs. A review of recent literature indicates growing research interest in applications for individuals who are elderly, inactive, or subject to medical conditions such as angina. (IAH)

  14. Perceived Exertion: An Old Exercise Tool Finds New Applications.

    ERIC Educational Resources Information Center

    Monahan, Terry

    1988-01-01

    Perceived exertion scales, based on subjective perception of energy output, are gaining respect as prescribing and monitoring tools for individual exercise programs. A review of recent literature indicates growing research interest in applications for individuals who are elderly, inactive, or subject to medical conditions such as angina. (IAH)

  15. 20 CFR 416.969a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., such as pain, may cause limitations of function or restrictions which limit your ability to meet... or restrictions imposed by your impairment(s) and related symptoms, such as pain, are exertional... imposed by your impairment(s) and related symptoms, such as pain, affect only your ability to meet...

  16. 20 CFR 416.969a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., such as pain, may cause limitations of function or restrictions which limit your ability to meet... or restrictions imposed by your impairment(s) and related symptoms, such as pain, are exertional... imposed by your impairment(s) and related symptoms, such as pain, affect only your ability to meet...

  17. 20 CFR 404.1567 - Physical exertion requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Physical exertion requirements. 404.1567 Section 404.1567 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... economy, we classify jobs as sedentary, light, medium, heavy, and very heavy. These terms have the same...

  18. 20 CFR 416.967 - Physical exertion requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Physical exertion requirements. 416.967 Section 416.967 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE... economy, we classify jobs as sedentary, light, medium, heavy, and very heavy. These terms have the same...

  19. Are the Measurements of Attention Allocation and Perceived Exertion Trustworthy?

    ERIC Educational Resources Information Center

    Meir, Gily; Hutchinson, Jasmin C.; Habeeb, Christine M.; Boiangin, Nataniel M.; Shaffer, Cory; Basevitch, Itay; Tenenbaum, Gershon

    2015-01-01

    Two studies examined the trustworthiness of commonly used measurement scales for ratings of perceived exertion (RPE) and state attentional focus (SAF) during exercise. In Study 1, participants (N = 24, 14 female) performed a treadmill graded-exercise test. The order of scale presentation during the task was manipulated (i.e., RPE followed by SAF…

  20. Are the Measurements of Attention Allocation and Perceived Exertion Trustworthy?

    ERIC Educational Resources Information Center

    Meir, Gily; Hutchinson, Jasmin C.; Habeeb, Christine M.; Boiangin, Nataniel M.; Shaffer, Cory; Basevitch, Itay; Tenenbaum, Gershon

    2015-01-01

    Two studies examined the trustworthiness of commonly used measurement scales for ratings of perceived exertion (RPE) and state attentional focus (SAF) during exercise. In Study 1, participants (N = 24, 14 female) performed a treadmill graded-exercise test. The order of scale presentation during the task was manipulated (i.e., RPE followed by SAF…

  1. Projection-specific neuromodulation of mPFC neurons

    PubMed Central

    Dembrow, Nikolai C.; Chitwood, Raymond A.; Johnston, Daniel

    2010-01-01

    Mnemonic persistent activity in the PFC constitutes the neural basis of working memory. To understand how neuromodulators contribute to the generation of persistent activity, it is necessary to identify the intrinsic properties of the layer V pyramidal neurons that transfer this information to downstream networks. Here we show that the somatic dynamic and integrative properties of layer V pyramidal neurons in the rat medial prefrontal cortex (mPFC) depend upon whether they project subcortically- to the pons (corticopontine, CPn) or to the contralateral cortex (commissural, COM). CPn neurons display low temporal summation and accelerate in firing frequency when depolarized, while COM neurons have high temporal summation and display spike frequency accommodation. In response to dynamic stimuli, COM neurons act as low-pass filters, whereas CPn neurons act as band-pass filters, resonating in the theta frequency range (3-6 Hz). The disparate subthreshold properties of COM and CPn neurons can be accounted for by differences in the hyperpolarization-activated cyclic nucleotide gated cation h-current. Interestingly, neuromodulators hypothesized to enhance mnemonic persistent activity affect COM and CPn neurons distinctly. Adrenergic modulation shifts the dynamic properties of CPn but not COM neurons, and increases the excitability of CPn neurons significantly more than COM neurons. In response to cholinergic modulation CPn neurons were much more likely to display activity-dependent intrinsic persistent firing than COM neurons. Together, these data suggest that the two categories of projection neurons may subserve separate functions in PFC and may be engaged differently during working memory processes. PMID:21159963

  2. Molecular genetics of mouse serotonin neurons across the lifespan

    PubMed Central

    Deneris, Evan S.

    2011-01-01

    New molecular genetics approaches have been developed over the past several years to study brain serotonin (5-HT) neuron development and the roles of 5-HT neurons in behavior and physiology. These approaches were enabled by manipulation of the gene encoding the Pet-1 ETS transcription factor whose expression in the brain is restricted to developing and adult 5-HT neurons. Targeting of the Pet-1 gene led to the development of a mouse line with a severe and stable deficiency of embryonic 5-HT-synthesizing neurons. The Pet-1 transcription regulatory region has been used to create several new 5-HT neuron-type transgenic tools that have greatly increased the experimental accessibility of the small number of brain 5-HT neurons. Permanent and specific marking of 5-HT neurons with Pet-1-based transgenic tools have now been used for flow cytometry, whole cell electrophysiological recordings, progenitor fate mapping and live time lapse imaging of these neurons. Additional tools provide multiple strategies for conditional temporal targeting of gene expression in 5-HT neurons at different stages of life. Pet-1 based approaches have led to advances in understanding the role of 5-HT neurons in respiration, thermoregulation, emotional behaviors, maternal behavior, and the mechanism of antipsychotic drug actions. In addition, these approaches have begun to reveal the molecular basis of 5-HT neuron heterogeneity and the transcriptional mechanisms that direct 5-HT neuron-type identity, maturation and maintenance. PMID:21920412

  3. Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

    PubMed Central

    Gavioli, Mariana; Lara, Aline; Almeida, Pedro W. M.; Lima, Augusto Martins; Damasceno, Denis D.; Rocha-Resende, Cibele; Ladeira, Marina; Resende, Rodrigo R.; Martinelli, Patricia M.; Melo, Marcos Barrouin; Brum, Patricia C.; Fontes, Marco Antonio Peliky; Souza Santos, Robson A.; Prado, Marco A. M.; Guatimosim, Silvia

    2014-01-01

    Cholinergic control of the heart is exerted by two distinct branches; the autonomic component represented by the parasympathetic nervous system, and the recently described non-neuronal cardiomyocyte cholinergic machinery. Previous evidence has shown that reduced cholinergic function leads to deleterious effects on the myocardium. Yet, whether conditions of increased cholinergic signaling can offset the pathological remodeling induced by sympathetic hyperactivity, and its consequences for these two cholinergic axes are unknown. Here, we investigated two models of sympathetic hyperactivity: i) the chronic beta-adrenergic receptor stimulation evoked by isoproterenol (ISO), and ii) the α2A/α2C-adrenergic receptor knockout (KO) mice that lack pre-synaptic adrenergic receptors. In both models, cholinergic signaling was increased by administration of the cholinesterase inhibitor, pyridostigmine. First, we observed that isoproterenol produces an autonomic imbalance characterized by increased sympathetic and reduced parasympathetic tone. Under this condition transcripts for cholinergic proteins were upregulated in ventricular myocytes, indicating that non-neuronal cholinergic machinery is activated during adrenergic overdrive. Pyridostigmine treatment prevented the effects of ISO on autonomic function and on the ventricular cholinergic machinery, and inhibited cardiac remodeling. α2A/α2C-KO mice presented reduced ventricular contraction when compared to wild-type mice, and this dysfunction was also reversed by cholinesterase inhibition. Thus, the cardiac parasympathetic system and non-neuronal cardiomyocyte cholinergic machinery are modulated in opposite directions under conditions of increased sympathetic drive or ACh availability. Moreover, our data support the idea that pyridostigmine by restoring ACh availability is beneficial in heart disease. PMID:24992197

  4. A new supervised learning algorithm for spiking neurons.

    PubMed

    Xu, Yan; Zeng, Xiaoqin; Zhong, Shuiming

    2013-06-01

    The purpose of supervised learning with temporal encoding for spiking neurons is to make the neurons emit a specific spike train encoded by the precise firing times of spikes. If only running time is considered, the supervised learning for a spiking neuron is equivalent to distinguishing the times of desired output spikes and the other time during the running process of the neuron through adjusting synaptic weights, which can be regarded as a classification problem. Based on this idea, this letter proposes a new supervised learning method for spiking neurons with temporal encoding; it first transforms the supervised learning into a classification problem and then solves the problem by using the perceptron learning rule. The experiment results show that the proposed method has higher learning accuracy and efficiency over the existing learning methods, so it is more powerful for solving complex and real-time problems.

  5. Estimating core temperature with external devices after exertional heat stress in thermal protective clothing.

    PubMed

    Pryor, Riana R; Seitz, Jennifer R; Morley, Julia; Suyama, Joe; Guyette, Francis X; Reis, Steven E; Hostler, David

    2012-01-01

    Temperature measurement is important for emergency medical services (EMS) providers when identifying and treating heat illness or infection. Direct measures of body core temperature (T(c)) are often expensive (ingestible capsules) or impractical (rectal probes) in the field. Multiple devices for estimating T(c) have been adopted by EMS providers, with little understanding of the agreement between these devices and T(c). To examine the agreement between the results of five external thermometers and T(c) after subjects experienced physical exertion while wearing protective clothing. Fifty firefighters completed treadmill walking in thermal protective clothing in a hot environment. Measurements of core, temporal, tympanic, forehead, and skin temperatures were obtained during a 20-minute recovery period simulating emergency incident rehabilitation. The mean bias of external thermometers ranged from -1.31°C to -3.28°C when compared with T(c) and exceeded the predetermined clinical cutoff of ±0.5°C from T(c). The 95% limits of agreement ranged from 2.75°C to 5.00°C. External measuring devices failed to accurately predict T(c) in hyperthermic individuals following exertion. Confidence intervals around the bias were too large to allow for reasonable estimation of T(c). EMS providers should exercise caution when using any of these temperature estimation techniques.

  6. Dynamics of Perceived Exertion in Constant-Power Cycling: Time- and Workload-Dependent Thresholds.

    PubMed

    Balagué, Natàlia; Hristovski, Robert; García, Sergi; Aguirre, Cecilia; Vázquez, Pablo; Razon, Selen; Tenenbaum, Gershon

    2015-01-01

    The purpose of this study was to test the dynamics of perceived exertion shifts (PES) as a function of time and workload during constant-power cycling. Fifty-two participants assigned to 4 groups performed a cycling task at 4 different constant workloads corresponding to their individual rates of perceived exertion (RPEs = 13, 15, 17, and 19, respectively). PES ("increased"/"decreased" perceptions) without magnitude were reported when they occurred. PES "increased" percentages in different nonoverlapping temporal windows and for each workload were calculated to study the time- and workload-dependent relations, respectively. A fluctuating PES dynamic characterized the cycling at RPE-13 and RPE-15. In contrast, a nonfluctuating PES dynamic characterized the cycling at RPE-17 and RPE-19. A time-dependent PES threshold, manifested as a switch from PES fluctuating to nonfluctuating dynamics, emerged in the RPE-15 condition near volitional exhaustion. A workload-dependent PES threshold occurred from RPE-15 to RPE-17. Time- and workload-dependent thresholds were revealed studying the PES dynamics in constant cycling. Monitoring PES can complement or provide an alternative to the use of physiological measures for an accurate control of training workloads.

  7. Gain, noise, and contrast sensitivity of linear visual neurons

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B.

    1990-01-01

    Contrast sensitivity is a measure of the ability of an observer to detect contrast signals of particular spatial and temporal frequencies. A formal definition of contrast sensitivity that can be applied to individual linear visual neurons is derived. A neuron is modeled by a contrast transfer function and its modulus, contrast gain, and by a noise power spectrum. The distributions of neural responses to signal and blank presentations are derived, and from these, a definition of contrast sensitivity is obtained. This formal definition may be used to relate the sensitivities of various populations of neurons, and to relate the sensitivities of neurons to that of the behaving animal.

  8. Calretinin Neurons in the Rat Suprachiasmatic Nucleus.

    PubMed

    Moore, Robert Y

    2016-08-01

    The hypothalamic suprachiasmatic nucleus (SCN), a circadian pacemaker, is present in all mammalian brains. It has a complex organization of peptide-containing neurons that is similar among species, but calcium-binding proteins are expressed variably. Neurons containing calretinin have been described in the SCN in a number of species but not with association to circadian function. The objective of the present study is to characterize a calretinin neuron (CAR) group in the rat anterior hypothalamus anatomically and functionally with a detailed description of its location and a quantitative analysis of neuronal calretinin immunoreactivity at 3 times of day, 0600, 1400, and 1900 h, from animals in either light-dark or constant dark conditions. CAR neurons occupy a region in the dorsal and lateral SCN with a circadian rhythm in CAR immunoreactivity with a peak at 0600 h and a rhythm in cytoplasmic CAR distribution with a peak at 1400 h. CAR neurons should be viewed as an anatomical and functional component of the rat SCN that expands the definition from observations with cell stains. CAR neurons are likely to modulate temporal regulation of calcium in synaptic transmission.

  9. Bayesian population decoding of spiking neurons.

    PubMed

    Gerwinn, Sebastian; Macke, Jakob; Bethge, Matthias

    2009-01-01

    The timing of action potentials in spiking neurons depends on the temporal dynamics of their inputs and contains information about temporal fluctuations in the stimulus. Leaky integrate-and-fire neurons constitute a popular class of encoding models, in which spike times depend directly on the temporal structure of the inputs. However, optimal decoding rules for these models have only been studied explicitly in the noiseless case. Here, we study decoding rules for probabilistic inference of a continuous stimulus from the spike times of a population of leaky integrate-and-fire neurons with threshold noise. We derive three algorithms for approximating the posterior distribution over stimuli as a function of the observed spike trains. In addition to a reconstruction of the stimulus we thus obtain an estimate of the uncertainty as well. Furthermore, we derive a 'spike-by-spike' online decoding scheme that recursively updates the posterior with the arrival of each new spike. We use these decoding rules to reconstruct time-varying stimuli represented by a Gaussian process from spike trains of single neurons as well as neural populations.

  10. A diversity of synaptic filters are created by temporal summation of excitation and inhibition

    PubMed Central

    George, Andrew A.; Lyons-Warren, Ariel M.; Ma, Xiaofeng; Carlson, Bruce A.

    2011-01-01

    Temporal filtering is a fundamental operation of nervous systems. In peripheral sensory systems, the temporal pattern of spiking activity can encode various stimulus qualities, and temporal filtering allows postsynaptic neurons to detect behaviorally-relevant stimulus features from these spike trains. Intrinsic excitability, short-term synaptic plasticity, and voltage-dependent dendritic conductances have all been identified as mechanisms that can establish temporal filtering behavior in single neurons. Here we show that synaptic integration of temporally-summating excitation and inhibition can establish diverse temporal filters of presynaptic input. Mormyrid electric fish communicate by varying the intervals between electric organ discharges. The timing of each discharge is coded by peripheral receptors into precisely-timed spikes. Within the midbrain posterior exterolateral nucleus, temporal filtering by individual neurons results in selective responses to a particular range of presynaptic interspike intervals. These neurons are diverse in their temporal filtering properties, reflecting the wide range of intervals that must be detected during natural communication behavior. By manipulating presynaptic spike timing with high temporal resolution, we demonstrate that tuning to behaviorally-relevant patterns of presynaptic input is similar in vivo and in vitro. We reveal that GABAergic inhibition plays a critical role in establishing different temporal filtering properties. Further, our results demonstrate that temporal summation of excitation and inhibition establishes selective responses to high and low rates of synaptic input, respectively. Simple models of synaptic integration reveal that variation in these two competing influences provides a basic mechanism for generating diverse temporal filters of synaptic input. PMID:21994388

  11. Identifying local and descending inputs for primary sensory neurons

    PubMed Central

    Zhang, Yi; Zhao, Shengli; Rodriguez, Erica; Takatoh, Jun; Han, Bao-Xia; Zhou, Xiang; Wang, Fan

    2015-01-01

    Primary pain and touch sensory neurons not only detect internal and external sensory stimuli, but also receive inputs from other neurons. However, the neuronal derived inputs for primary neurons have not been systematically identified. Using a monosynaptic rabies viruses–based transneuronal tracing method combined with sensory-specific Cre-drivers, we found that sensory neurons receive intraganglion, intraspinal, and supraspinal inputs, the latter of which are mainly derived from the rostroventral medulla (RVM). The viral-traced central neurons were largely inhibitory but also consisted of some glutamatergic neurons in the spinal cord and serotonergic neurons in the RVM. The majority of RVM-derived descending inputs were dual GABAergic and enkephalinergic (opioidergic). These inputs projected through the dorsolateral funiculus and primarily innervated layers I, II, and V of the dorsal horn, where pain-sensory afferents terminate. Silencing or activation of the dual GABA/enkephalinergic RVM neurons in adult animals substantially increased or decreased behavioral sensitivity, respectively, to heat and mechanical stimuli. These results are consistent with the fact that both GABA and enkephalin can exert presynaptic inhibition of the sensory afferents. Taken together, this work provides a systematic view of and a set of tools for examining peri- and extrasynaptic regulations of pain-afferent transmission. PMID:26426077

  12. Atrophy and neuron loss: effects of a protein-deficient diet on sympathetic neurons.

    PubMed

    Gomes, Silvio Pires; Nyengaard, Jens Randel; Misawa, Rúbia; Girotti, Priscila Azevedo; Castelucci, Patrìcia; Blazquez, Francisco Hernandez Javier; de Melo, Mariana Pereira; Ribeiro, Antonio Augusto Coppi

    2009-12-01

    Protein deficiency is one of the biggest public health problems in the world, accounting for about 30-40% of hospital admissions in developing countries. Nutritional deficiencies lead to alterations in the peripheral nervous system and in the digestive system. Most studies have focused on the effects of protein-deficient diets on the enteric neurons, but not on sympathetic ganglia, which supply extrinsic sympathetic input to the digestive system. Hence, in this study, we investigated whether a protein-restricted diet would affect the quantitative structure of rat coeliac ganglion neurons. Five male Wistar rats (undernourished group) were given a pre- and postnatal hypoproteinic diet receiving 5% casein, whereas the nourished group (n = 5) was fed with 20% casein (normoproteinic diet). Blood tests were carried out on the animals, e.g., glucose, leptin, and triglyceride plasma concentrations. The main structural findings in this study were that a protein-deficient diet (5% casein) caused coeliac ganglion (78%) and coeliac ganglion neurons (24%) to atrophy and led to neuron loss (63%). Therefore, the fall in the total number of coeliac ganglion neurons in protein-restricted rats contrasts strongly with no neuron losses previously described for the enteric neurons of animals subjected to similar protein-restriction diets. Discrepancies between our figures and the data for enteric neurons (using very similar protein-restriction protocols) may be attributable to the counting method used. In light of this, further systematic investigations comparing 2-D and 3-D quantitative methods are warranted to provide even more advanced data on the effects that a protein-deficient diet may exert on sympathetic neurons. (c) 2009 Wiley-Liss, Inc.

  13. Wall pressure exerted by hydrogenation of sodium aluminum hydride.

    SciTech Connect

    Perras, Yon E.; Dedrick, Daniel E.; Zimmerman, Mark D.

    2009-06-01

    Wall pressure exerted by the bulk expansion of a sodium aluminum hydride bed was measured as a function of hydrogen content. A custom apparatus was designed and loaded with sodium alanates at densities of 1.0, 1.1, and 1.16 g/cc. Four complete cycles were performed to identify variations in measured pressure. Results indicated poor correlation between exerted pressure and hydrogen capacity of the sodium alanate beds. Mechanical pressure due to the hydrogenation of sodium alanates does not influence full-scale system designs as it falls within common design factors of safety. Gas pressure gradients within the porous solid were identified and may limit reaction rates, especially for high aspect ratio beds.

  14. Exertional dyspnea as a symptom of infrarenal aortic occlusive disease.

    PubMed

    Schott, Stacey L; Carreiro, Fernanda Porto; Harkness, James R; Malas, Mahmoud B; Sozio, Stephen M; Zakaria, Sammy

    2014-06-01

    Advanced atherosclerosis of the aorta can cause severe ischemia in the kidneys, refractory hypertension, and claudication. However, no previous reports have clearly associated infrarenal aortic stenosis with shortness of breath. A 77-year-old woman with hypertension and hyperlipidemia presented with exertional dyspnea. Despite extensive testing and observation, no apparent cause for this patient's dyspnea was found. Images revealed severe infrarenal aortic stenosis. After the patient underwent stenting of the aortic occlusion, she had immediate symptomatic improvement and complete resolution of her dyspnea within one month. Twelve months after vascular intervention, the patient remained asymptomatic. In view of the distinct and lasting elimination of dyspnea after angioplasty and stenting of a nearly occluded infrarenal aortic lesion, we hypothesize that infrarenal aortic stenosis might be a treatable cause of exertional dyspnea. Clinicians should consider infrarenal aortic stenosis as a possible cause of dyspnea. Treatment of the stenosis might relieve symptoms.

  15. Endoscopic Thermal Fasciotomy for Chronic Exertional Compartment Syndrome

    PubMed Central

    Voleti, Pramod B.; Lebrun, Drake G.; Roth, Cameron A.; Kelly, John D.

    2015-01-01

    Chronic exertional compartment syndrome is an activity-induced condition that occurs when intracompartmental pressures within an osteofascial envelope increase during exercise, leading to reversible ischemic symptoms such as pain, cramping, numbness, or weakness. Nonoperative treatment options for this condition have shown limited success and are often undesirable for the patient given the requirement for activity modification. Traditional surgical treatment options involving open or subcutaneous fasciotomies have more favorable results, but these techniques are associated with significant morbidity. Endoscopically assisted fasciotomy techniques afford the advantages of being minimally invasive, providing excellent visualization, and allowing accelerated rehabilitation. The purpose of this article is to describe a technique for performing endoscopically assisted fasciotomies for chronic exertional compartment syndrome of the lower leg using an entirely endoscopic thermal ablating device. The endoscopic thermal fasciotomy technique is associated with minimal morbidity, ensures excellent hemostasis, and affords an early return to sports. PMID:26900549

  16. Aural Canal, Esophageal, and Rectal Temperatures During Exertional Heat Stress and the Subsequent Recovery Period

    PubMed Central

    Gagnon, Daniel; Lemire, Bruno B.; Jay, Ollie; Kenny, Glen P.

    2010-01-01

    Abstract Context: The measurement of body temperature is crucial for the initial diagnosis of exertional heat injury and for monitoring purposes during a subsequent treatment strategy. However, little information is available about how different measurements of body temperature respond during and after exertional heat stress. Objective: To present the temporal responses of aural canal (Tac), esophageal (Tes), and rectal (Tre) temperatures during 2 different scenarios (S1, S2) involving exertional heat stress and a subsequent recovery period. Design: Randomized controlled trial. Setting: University research laboratory. Patients or Other Participants: Twenty-four healthy volunteers, with 12 (5 men, 7 women) participating in S1 and 12 (7 men, 5 women) participating in S2. Intervention(s): The participants exercised in the heat (42°C, 30% relative humidity) until they reached a 39.5°C cut-off criterion, which was determined by Tre in S1 and by Tes in S2. As such, participants attained different levels of hyperthermia (as determined by Tre) at the end of exercise. Participants in S1 were subsequently immersed in cold water (2°C) until Tre reached 37.5°C, and participants in S2 recovered in a temperate environment (30°C, 30% relative humidity) for 60 minutes. Main Outcome Measure(s): We measured Tac, Tes, and Tre throughout both scenarios. Results: The Tes (S1  =  40.19 ± 0.41°C, S2  =  39.50 ± 0.02°C) was higher at the end of exercise compared with both Tac (S1  =  39.74 ± 0.42°C, S2  =  38.89 ± 0.32°C) and Tre (S1  =  39.41 ± 0.04°C, S2  =  38.74 ± 0.28°C) (for both comparisons in each scenario, P < .001). Conversely, Tes (S1  =  36.26 ± 0.74°C, S2  =  37.36 ± 0.34°C) and Tac (S1  =  36.48 ± 1.07°C, S2  =  36.97 ± 0.38°C) were lower compared with Tre (S1  =  37.54 ± 0.04°C, S2  =  37.78 ± 0.31°C) at the end of both scenarios (for both comparisons in each scenario, P < .001). Conclusions: We

  17. Cytokine immunoreactivity in cortical and subcortical neurons in periventricular leukomalacia: are cytokines implicated in neuronal dysfunction in cerebral palsy?

    PubMed

    Kadhim, Hazim; Tabarki, Brahim; De Prez, Carine; Sébire, Guillaume

    2003-03-01

    The major neuropathological substrate associated with cerebral palsy (CP) is a form of white matter (WM) injury known as periventricular leukomalacia (PVL). Proinflammatory cytokines were recently shown to be implicated in PVL pathogenesis. Many PVL patients develop cortical and deep gray neuronal dysfunctions such as epilepsy, cognitive deficits and extrapyramidal disorders. The precise nature of the relationship between the WM lesion and the subsequent neuronal disorders is unclear. Cytokines were shown to exert neurotoxicity in experimental models. This raises the need to investigate a possible noxious effect by cytokines on neuronal cortical development. In situ immunohistochemical methods were applied on 22 brains from infants both with PVL (study group) and without PVL (control group) to detect any immunoreactivity for cytokines (TNF-alpha, IL-1beta, IL-6) in cortical and gray matter neurons. While cortical and other neuronal structures in PVL brains did not display noticeable pathological anomalies, strong cytokine immunoreactivity was detected in many neurons in the neocortex, hippocampus, basal ganglia and thalamus. There were, however, regional differences in cytokine labeling. In addition, there was more TNF-alpha staining than IL-1beta; IL-6 was negative. In contrast, neuronal cytokine labeling in the "control" brains was negligible. In conclusion, we report and characterize, for the first time, the in situ immunoreactivity for proinflammatory cytokines in cortical and deep gray neurons in PVL. These findings might provide insights into the neuro-anatomical correlate for the intellectual deficits and the other cortical and deep gray neuronal dysfunctions associated with PVL.

  18. Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons

    PubMed Central

    Dagostin, André A.; Lovell, Peter V.; Hilscher, Markus M.; Mello, Claudio V.; Leão, Ricardo M.

    2015-01-01

    Central neurons express a variety of neuronal types and ion channels that promote firing heterogeneity among their distinct neuronal populations. Action potential (AP) phasic firing, produced by low-threshold voltage-activated potassium currents (VAKCs), is commonly observed in mammalian brainstem neurons involved in the processing of temporal properties of the acoustic information. The avian caudomedial nidopallium (NCM) is an auditory area analogous to portions of the mammalian auditory cortex that is involved in the perceptual discrimination and memorization of birdsong and shows complex responses to auditory stimuli We performed in vitro whole-cell patch-clamp recordings in brain slices from adult zebra finches (Taeniopygia guttata) and observed that half of NCM neurons fire APs phasically in response to membrane depolarizations, while the rest fire transiently or tonically. Phasic neurons fired APs faster and with more temporal precision than tonic and transient neurons. These neurons had similar membrane resting potentials, but phasic neurons had lower membrane input resistance and time constant. Surprisingly phasic neurons did not express low-threshold VAKCs, which curtailed firing in phasic mammalian brainstem neurons, having similar VAKCs to other NCM neurons. The phasic firing was determined not by VAKCs, but by the potassium background leak conductances, which was more prominently expressed in phasic neurons, a result corroborated by pharmacological, dynamic-clamp, and modeling experiments. These results reveal a new role for leak currents in generating firing diversity in central neurons. PMID:26696830

  19. Failing phrenics: an obscure cause of exertional dyspnea

    PubMed Central

    Rafiq, Arsalan; Ijaz, Mohsin; Tariq, Hassan; Vakde, Trupti; Duncalf, Richard

    2016-01-01

    Abstract Introduction: Idiopathic phrenic nerve palsy is a rare cause of exertional dyspnea. We present a case of a patient presenting with worsening dyspnea of an unknown etiology found to be related to bilateral phrenic nerve palsy. Discussion: Forty-two-year-old man presented to our emergency department with exertional dyspnea, orthopnea, and a left lower lobe consolidation treated initially as bronchitis by his primary physician as an outpatient, then subsequently as pneumonia at another institution, with no improvement in symptomatology. After admission to our hospital, CT chest demonstrated only supradiaphragmatic atelectatic changes. Echocardiography was normal. Bronchoscopy was contemplated however the patient could not lie flat. A fluoroscopic sniff test demonstrated diaphragmatic dysfunction and pulmonary function tests revealed restrictive pulmonary disease with evidence of neuromuscular etiology. Nerve conduction studies confirmed bilateral phrenic neuropathy. He was referred to a specialized neuromuscular disease center where subsequent workup did not demonstrate any specific etiology. A sleep study confirmed sleep disordered breathing suggestive of diaphragmatic paralysis and he was discharged on bi-level positive pressure ventilation. Conclusion: This is a unique case of exertional dyspnea and orthopnea from diaphragmatic paresis caused by bilateral phrenic nerve palsy where the initial workup for pulmonary and cardiovascular etiologies was essentially unremarkable. Shortness of breath and orthopnea caused by phrenic neuropathy is a rare condition, yet has a variety of etiologies. Our case suggests a template to the diagnostic approach, management, and follow up of bilateral phrenic nerve palsy. PMID:27442657

  20. Exercise, physical activity, and exertion over the business cycle.

    PubMed

    Colman, Gregory; Dave, Dhaval

    2013-09-01

    Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes.

  1. Fractional Cable Models for Spiny Neuronal Dendrites

    NASA Astrophysics Data System (ADS)

    Henry, B. I.; Langlands, T. A. M.; Wearne, S. L.

    2008-03-01

    Cable equations with fractional order temporal operators are introduced to model electrotonic properties of spiny neuronal dendrites. These equations are derived from Nernst-Planck equations with fractional order operators to model the anomalous subdiffusion that arises from trapping properties of dendritic spines. The fractional cable models predict that postsynaptic potentials propagating along dendrites with larger spine densities can arrive at the soma faster and be sustained at higher levels over longer times. Calibration and validation of the models should provide new insight into the functional implications of altered neuronal spine densities, a hallmark of normal aging and many neurodegenerative disorders.

  2. Neuronal Complexity in Subthalamic Nucleus is Reduced in Parkinson's Disease.

    PubMed

    Vyas, Saurabh; Huang, He; Gale, John T; Sarma, Sridevi V; Montgomery, Erwin B

    2016-01-01

    Several theories posit increased Subthalamic Nucleus (STN) activity is causal to Parkinsonism, yet in our previous study we showed that activity from 113 STN neurons from two epilepsy patients and 103 neurons from nine Parkinson's disease (PD) patients demonstrated no significant differences in frequencies or in the coefficients of variation of mean discharge frequencies per 1-s epochs. We continued our analysis using point process modeling to capture higher order temporal dynamics; in particular, bursting, beta-band oscillations, excitatory and inhibitory ensemble interactions, and neuronal complexity. We used this analysis as input to a logistic regression classifier and were able to differentiate between PD and epilepsy neurons with an accuracy of 92%. We also found neuronal complexity, i.e., the number of states in a neuron's point process model, and inhibitory ensemble dynamics, which can be interpreted as a reduction in complexity, to be the most important features with respect to classification accuracy. Even in a dataset with no significant differences in firing rate, we observed differences between PD and epilepsy for other single-neuron measures. Our results suggest PD comes with a reduction in neuronal "complexity," which translates to a neuron's ability to encode information; the more complexity, the more information the neuron can encode. This is also consistent with studies correlating disease to loss of variability in neuronal activity, as the lower the complexity, the less variability.

  3. 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

  4. Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy.

    PubMed

    Tchekalarova, Jana D; Ivanova, Natasha; Atanasova, Dimitrina; Pechlivanova, Daniela M; Lazarov, Nikolai; Kortenska, Lidia; Mitreva, Rumiana; Lozanov, Valentin; Stoynev, Alexander

    2016-08-01

    Over the last 10 years, accumulated experimental and clinical evidence has supported the idea that AT1 receptor subtype is involved in epilepsy. Recently, we have shown that the selective AT1 receptor antagonist losartan attenuates epileptogenesis and exerts neuroprotection in the CA1 area of the hippocampus in epileptic Wistar rats. This study aimed to verify the efficacy of long-term treatment with losartan (10 mg/kg) after kainate-induced status epilepticus (SE) on seizure activity, behavioral and biochemical changes, and neuronal damage in a model of co-morbid hypertension and epilepsy. Spontaneous seizures were video- and EEG-monitored in spontaneously hypertensive rats (SHRs) for a 16-week period after SE. The behavior was analyzed by open field, elevated plus maze, sugar preference test, and forced swim test. The levels of serotonin in the hippocampus and neuronal loss were estimated by HPLC and hematoxylin and eosin staining, respectively. The AT1 receptor antagonism delayed the onset of seizures and alleviated their frequency and duration during and after discontinuation of treatment. Losartan showed neuroprotection mostly in the CA3 area of the hippocampus and the septo-temporal hilus of the dentate gyrus in SHRs. However, the AT1 receptor antagonist did not exert a substantial influence on concomitant with epilepsy behavioral changes and decreased 5-HT levels in the hippocampus. Our results suggest that the antihypertensive therapy with an AT1 receptor blocker might be effective against seizure activity and neuronal damage in a co-morbid hypertension and epilepsy.

  5. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    PubMed Central

    Homberg, Judith R.; Olivier, Jocelien D. A.; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine

  6. Temporal mapping and analysis

    NASA Technical Reports Server (NTRS)

    O'Hara, Charles G. (Inventor); Shrestha, Bijay (Inventor); Vijayaraj, Veeraraghavan (Inventor); Mali, Preeti (Inventor)

    2011-01-01

    A compositing process for selecting spatial data collected over a period of time, creating temporal data cubes from the spatial data, and processing and/or analyzing the data using temporal mapping algebra functions. In some embodiments, the temporal data cube is creating a masked cube using the data cubes, and computing a composite from the masked cube by using temporal mapping algebra.

  7. Time-warp invariant pattern detection with bursting neurons

    NASA Astrophysics Data System (ADS)

    Gollisch, Tim

    2008-01-01

    Sound patterns are defined by the temporal relations of their constituents, individual acoustic cues. Auditory systems need to extract these temporal relations to detect or classify sounds. In various cases, ranging from human speech to communication signals of grasshoppers, this pattern detection has been found to display invariance to temporal stretching or compression of the sound signal ('linear time-warp invariance'). In this work, a four-neuron network model is introduced, designed to solve such a detection task for the example of grasshopper courtship songs. As an essential ingredient, the network contains neurons with intrinsic bursting dynamics, which allow them to encode durations between acoustic events in short, rapid sequences of spikes. As shown by analytical calculations and computer simulations, these neuronal dynamics result in a powerful mechanism for temporal integration. Finally, the network reads out the encoded temporal information by detecting equal activity of two such bursting neurons. This leads to the recognition of rhythmic patterns independent of temporal stretching or compression.

  8. Associative Memory Neural Network with Low Temporal Spiking Rates

    NASA Astrophysics Data System (ADS)

    Amit, Daniel J.; Treves, A.

    1989-10-01

    We describe a modified attractor neural network in which neuronal dynamics takes place on a time scale of the absolute refractory period but the mean temporal firing rate of any neuron in the network is lower by an arbitrary factor that characterizes the strength of the effective inhibition. It operates by encoding information on the excitatory neurons only and assuming the inhibitory neurons to be faster and to inhibit the excitatory ones by an effective postsynaptic potential that is expressed in terms of the activity of the excitatory neurons themselves. Retrieval is identified as a nonergodic behavior of the network whose consecutive states have a significantly enhanced activity rate for the neurons that should be active in a stored pattern and a reduced activity rate for the neurons that are inactive in the memorized pattern. In contrast to the Hopfield model the network operates away from fixed points and under the strong influence of noise. As a consequence, of the neurons that should be active in a pattern, only a small fraction is active in any given time cycle and those are randomly distributed, leading to reduced temporal rates. We argue that this model brings neural network models much closer to biological reality. We present the results of detailed analysis of the model as well as simulations.

  9. Temporal identity in axonal target layer recognition.

    PubMed

    Petrovic, Milan; Hummel, Thomas

    2008-12-11

    The segregation of axon and dendrite projections into distinct synaptic layers is a fundamental principle of nervous system organization and the structural basis for information processing in the brain. Layer-specific recognition molecules that allow projecting neurons to stabilize transient contacts and initiate synaptogenesis have been identified. However, most of the neuronal cell-surface molecules critical for layer organization are expressed broadly in the developing nervous system, raising the question of how these so-called permissive adhesion molecules support synaptic specificity. Here we show that the temporal expression dynamics of the zinc-finger protein sequoia is the major determinant of Drosophila photoreceptor connectivity into distinct synaptic layers. Neighbouring R8 and R7 photoreceptors show consecutive peaks of elevated sequoia expression, which correspond to their sequential target-layer innervation. Loss of sequoia in R7 leads to a projection switch into the R8 recipient layer, whereas a prolonged expression in R8 induces a redirection of their axons into the R7 layer. The sequoia-induced axon targeting is mediated through the ubiquitously expressed Cadherin-N cell adhesion molecule. Our data support a model in which recognition specificity during synaptic layer formation is generated through a temporally restricted axonal competence to respond to broadly expressed adhesion molecules. Because developing neurons innervating the same target area often project in a distinct, birth-order-dependent sequence, temporal identity seems to contain crucial information in generating not only cell type diversity during neuronal division but also connection diversity of projecting neurons.

  10. Neurofibromin and Neuronal Apoptosis

    DTIC Science & Technology

    2005-07-01

    for these differences in the response of Nfl-/- neurons. "So What" Section. The learning disabilities associated with NF I constitute a highly variable...and +/+ neurons appear to become more significant with age. Our results may have implications for two areas: 1) the pathogenesis of learning ... disabilities in children with NF I, and 2) therapeutic strategies or targets for prolonging neuron survival, or for increasing neuronal response to protective

  11. AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

    PubMed

    Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

    2017-09-06

    To maintain energy homeostasis, orexigenic (appetite-inducing) and anorexigenic (appetite suppressing) brain systems functionally interact to regulate food intake. Within the hypothalamus, neurons that express agouti-related protein (AgRP) sense orexigenic factors and orchestrate an increase in food-seeking behavior. In contrast, calcitonin gene-related peptide (CGRP)-expressing neurons in the parabrachial nucleus (PBN) suppress feeding. PBN CGRP neurons become active in response to anorexigenic hormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (CCK), secreted by the small intestine. Additionally, exogenous compounds, such as lithium chloride (LiCl), a salt that creates gastric discomfort, and lipopolysaccharide (LPS), a bacterial cell wall component that induces inflammation, exert appetite-suppressing effects and activate PBN CGRP neurons. The effects of increasing the homeostatic drive to eat on feeding behavior during appetite suppressing conditions are unknown. Here, we show in mice that food deprivation or optogenetic activation of AgRP neurons induces feeding to overcome the appetite suppressing effects of amylin, CCK, and LiCl, but not LPS. AgRP neuron photostimulation can also increase feeding during chemogenetic-mediated stimulation of PBN CGRP neurons. AgRP neuron stimulation reduces Fos expression in PBN CGRP neurons across all conditions. Finally, stimulation of projections from AgRP neurons to the PBN increases feeding following administration of amylin, CCK, and LiCl, but not LPS. These results demonstrate that AgRP neurons are sufficient to increase feeding during noninflammatory-based appetite suppression and to decrease activity in anorexigenic PBN CGRP neurons, thereby increasing food intake during homeostatic need.SIGNIFICANCE STATEMENT The motivation to eat depends on the relative balance of activity in distinct brain regions that induce or suppress appetite. An abnormal amount of activity in

  12. Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity.

    PubMed

    Corty, Megan M; Freeman, Marc R

    2013-11-11

    Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

  13. Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon.

    PubMed

    Baccari, M C; Traini, C; Garella, R; Cipriani, G; Vannucchi, M G

    2012-11-01

    The hormone relaxin exerts a variety of functions on the smooth muscle of reproductive and nonreproductive organs, most of which occur through a nitric oxide (NO)-mediated mechanism. In the stomach and ileum, relaxin causes muscle relaxation by modulating the activity and expression of different nitric oxide synthase (NOS) isoforms region-dependently. Nothing is known on the effects of relaxin in the colon, the gut region expressing the highest number of neuronal (n) NOSβ-immunoreactive neurons and mainly involved in motor symptoms of pregnancy and menstrual cycle. Therefore, we studied the effects of relaxin exposure in the mouse proximal colon in vitro evaluating muscle mechanical activity and NOS isoform expression. The functional experiments showed that relaxin decreases muscle tone and increases amplitude of spontaneous contractions; the immunohistochemical results showed that relaxin increases nNOSβ and endothelial (e) NOS expression in the neurons and decreases nNOSα and eNOS expression in the smooth muscle cells (SMC). We hypothesized that, in the colon, relaxin primarily increases the activity and expression of nNOSβ and eNOS in the neurons, causing a reduction of the muscle tone. The downregulation of nNOSα and eNOS expression in the SMC associated with increased muscle contractility could be the consequence of continuous exposue of these cells to the NO of neuronal origin. These findings may help to better understand the physiology of NO in the gastrointestinal tract and the role that the "relaxin-NO" system plays in motor disorders such as functional bowel disease.

  14. Coherent neuronal ensembles are rapidly recruited when making a look-reach decision.

    PubMed

    Wong, Yan T; Fabiszak, Margaret M; Novikov, Yevgeny; Daw, Nathaniel D; Pesaran, Bijan

    2016-02-01

    Selecting and planning actions recruits neurons across many areas of the brain, but how ensembles of neurons work together to make decisions is unknown. Temporally coherent neural activity may provide a mechanism by which neurons coordinate their activity to make decisions. If so, neurons that are part of coherent ensembles may predict movement choices before other ensembles of neurons. We recorded neuronal activity in the lateral and medial banks of the intraparietal sulcus (IPS) of the posterior parietal cortex while monkeys made choices about where to look and reach. We decoded the activity to predict the choices. Ensembles of neurons that displayed coherent patterns of spiking activity extending across the IPS--'dual-coherent' ensembles--predicted movement choices substantially earlier than other neuronal ensembles. We propose that dual-coherent spike timing reflects interactions between groups of neurons that are important to decisions.

  15. Coherent neuronal ensembles are rapidly recruited when making a look-reach decision

    PubMed Central

    Wong, Yan T.; Fabiszak, Margaret M.; Novikov, Yevgeny; Daw, Nathaniel D.; Pesaran, Bijan

    2015-01-01

    Summary Selecting and planning actions recruits neurons across many areas of the brain but how ensembles of neurons work together to make decisions is unknown. Temporally-coherent neural activity may provide a mechanism by which neurons coordinate their activity in order to make decisions. If so, neurons that are part of coherent ensembles may predict movement choices before other ensembles of neurons. We recorded neuronal activity in the lateral and medial banks of the intraparietal sulcus (IPS) of the posterior parietal cortex, while monkeys made choices about where to look and reach and decoded the activity to predict the choices. Ensembles of neurons that displayed coherent patterns of spiking activity extending across the IPS, “dual coherent” ensembles, predicted movement choices substantially earlier than other neuronal ensembles. We propose that dual-coherent spike timing reflects interactions between groups of neurons that play an important role in how we make decisions. PMID:26752158

  16. Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination.

    PubMed

    Personius, Kirkwood E; Chang, Qiang; Mentis, George Z; O'Donovan, Michael J; Balice-Gordon, Rita J

    2007-07-10

    During late embryonic and early postnatal life, neuromuscular junctions undergo synapse elimination that is modulated by patterns of motor neuron activity. Here, we test the hypothesis that reduced spinal neuron gap junctional coupling decreases temporally correlated motor neuron activity that, in turn, modulates neuromuscular synapse elimination, by using mutant mice lacking connexin 40 (Cx40), a developmentally regulated gap junction protein expressed in motor and other spinal neurons. In Cx40-/- mice, electrical coupling among lumbar motor neurons, measured by whole-cell recordings, was reduced, and single motor unit recordings in awake, behaving neonates showed that temporally correlated motor neuron activity was also reduced. Immunostaining and intracellular recording showed that the neuromuscular synapse elimination was accelerated in muscles from Cx40-/- mice compared with WT littermates. Our work shows that gap junctional coupling modulates neuronal activity patterns that, in turn, mediate synaptic competition, a process that shapes synaptic circuitry in the developing brain.

  17. Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination

    PubMed Central

    Personius, Kirkwood E.; Chang, Qiang; Mentis, George Z.; O'Donovan, Michael J.; Balice-Gordon, Rita J.

    2007-01-01

    During late embryonic and early postnatal life, neuromuscular junctions undergo synapse elimination that is modulated by patterns of motor neuron activity. Here, we test the hypothesis that reduced spinal neuron gap junctional coupling decreases temporally correlated motor neuron activity that, in turn, modulates neuromuscular synapse elimination, by using mutant mice lacking connexin 40 (Cx40), a developmentally regulated gap junction protein expressed in motor and other spinal neurons. In Cx40−/− mice, electrical coupling among lumbar motor neurons, measured by whole-cell recordings, was reduced, and single motor unit recordings in awake, behaving neonates showed that temporally correlated motor neuron activity was also reduced. Immunostaining and intracellular recording showed that the neuromuscular synapse elimination was accelerated in muscles from Cx40−/− mice compared with WT littermates. Our work shows that gap junctional coupling modulates neuronal activity patterns that, in turn, mediate synaptic competition, a process that shapes synaptic circuitry in the developing brain. PMID:17609378

  18. Wheelchair users' perceived exertion during typical mobility activities.

    PubMed

    Qi, L; Ferguson-Pell, M; Salimi, Z; Haennel, R; Ramadi, A

    2015-09-01

    Each participant performed a series of wheelchair exercises equivalent in intensity to minimal functional speed (1 m s(-1)), functional walking speed (1.3 m s(-1)), a relatively challenging speed (1.6 m s(-1)) and a self-selected speed. Each participant also completed a graded exercise test (GXT) to volitional exhaustion (VO2peak). The purpose of this study was (1) to assess the physical capacity of wheelchair users as they undertake typical mobility activities and (2) to investigate how closely the components of a differentiated model of perceived exertion mirror wheelchair users' own perception of exertion. Eleven (eight males and three females) spinal cord-injured or congenitally impaired wheelchair-dependent participants volunteered for the study. Differentiated ratings of perceived exertion (RPE_arm and RPE_respiration) and oxygen uptake (VO2) and heart rate were recorded during each exercise. The mean comfortable speed at which the participants propelled their own wheelchairs on the wheelchair ergometer was 1.1±0.2 m s(-1). Speeds of 1 m s(-1) and 1.3 m s(-1) are typical of everyday functional propulsion. The corresponding RPE_respiration and RPE_arm ranged from 7 to 13 on the Borg scale; the %VO2peak measured in these trials ranged from 37 to 80% VO2peak. For propulsion intensities used in the present study-low, moderate, high and graded exercise intensity-no difference could be observed between RPE_respiration and RPE_arm. There were no significant differences between RPE_arm and RPE_respiration at the termination of the GXT. The current study showed potential for the use of RPE to assess and monitor daily wheelchair propulsion intensity in individuals with paraplegia.

  19. A virtual rat for simulating environmental and exertional heat stress.

    PubMed

    Rakesh, Vineet; Stallings, Jonathan D; Reifman, Jaques

    2014-12-01

    Severe cases of environmental or exertional heat stress can lead to varying degrees of organ dysfunction. To understand heat-injury progression and develop efficient management and mitigation strategies, it is critical to determine the thermal response in susceptible organs under different heat-stress conditions. To this end, we used our previously published virtual rat, which is capable of computing the spatiotemporal temperature distribution in the animal, and extended it to simulate various heat-stress scenarios, including 1) different environmental conditions, 2) exertional heat stress, 3) circadian rhythm effect on the thermal response, and 4) whole body cooling. Our predictions were consistent with published in vivo temperature measurements for all cases, validating our simulations. We observed a differential thermal response in the organs, with the liver experiencing the highest temperatures for all environmental and exertional heat-stress cases. For every 3°C rise in the external temperature from 40 to 46°C, core and organ temperatures increased by ∼0.8°C. Core temperatures increased by 2.6 and 4.1°C for increases in exercise intensity from rest to 75 and 100% of maximal O2 consumption, respectively. We also found differences as large as 0.8°C in organ temperatures for the same heat stress induced at different times during the day. Even after whole body cooling at a relatively low external temperature (1°C for 20 min), average organ temperatures were still elevated by 2.3 to 2.5°C compared with normothermia. These results can be used to optimize experimental protocol designs, reduce the amount of animal experimentation, and design and test improved heat-stress prevention and management strategies.

  20. Pressure garment design tool to monitor exerted pressures.

    PubMed

    Macintyre, Lisa; Ferguson, Rhona

    2013-09-01

    Pressure garments are used in the treatment of hypertrophic scarring following serious burns. The use of pressure garments is believed to hasten the maturation process, reduce pruritus associated with immature hypertrophic scars and prevent the formation of contractures over flexor joints. Pressure garments are normally made to measure for individual patients from elastic fabrics and are worn continuously for up to 2 years or until scar maturation. There are 2 methods of constructing pressure garments. The most common method, called the Reduction Factor method, involves reducing the patient's circumferential measurements by a certain percentage. The second method uses the Laplace Law to calculate the dimensions of pressure garments based on the circumferential measurements of the patient and the tension profile of the fabric. The Laplace Law method is complicated to utilise manually and no design tool is currently available to aid this process. This paper presents the development and suggested use of 2 new pressure garment design tools that will aid pressure garment design using the Reduction Factor and Laplace Law methods. Both tools calculate the pressure garment dimensions and the mean pressure that will be exerted around the body at each measurement point. Monitoring the pressures exerted by pressure garments and noting the clinical outcome would enable clinicians to build an understanding of the implications of particular pressures on scar outcome, maturation times and patient compliance rates. Once the optimum pressure for particular treatments is known, the Laplace Law method described in this paper can be used to deliver those average pressures to all patients. This paper also presents the results of a small scale audit of measurements taken for the fabrication of pressure garments in two UK hospitals. This audit highlights the wide range of pressures that are exerted using the Reduction Factor method and that manual pattern 'smoothing' can dramatically

  1. Nonspatial Sequence Coding in CA1 Neurons

    PubMed Central

    Allen, Timothy A.; Salz, Daniel M.; McKenzie, Sam

    2016-01-01

    The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequence-memory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as “in sequence” or “out of sequence”. We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items—in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe-specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20–40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4–12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus. SIGNIFICANCE STATEMENT The ability to remember the order of life events depends on the hippocampus, but the underlying neural mechanisms remain poorly understood. Here we addressed this issue by recording neural activity in hippocampal

  2. Loss of nonphosphorylated neurofilament immunoreactivity in temporal cortical areas in Alzheimer's disease.

    PubMed

    Thangavel, R; Sahu, S K; Van Hoesen, G W; Zaheer, A

    2009-05-05

    The distribution of immunoreactive neurons with nonphosphorylated neurofilament protein (SMI32) was studied in temporal cortical areas in normal subjects and in patients with Alzheimer's disease (AD). SMI32 immunopositive neurons were localized mainly in cortical layers II, III, V and VI, and were medium to large-sized pyramidal neurons. Patients with AD had prominent degeneration of SMI32 positive neurons in layers III and V of Brodmann areas 38, 36, 35 and 20; in layers II and IV of the entorhinal cortex (Brodmann area 28); and hippocampal neurons. Neurofibrillary tangles (NFTs) were stained with Thioflavin-S and with an antibody (AT8) against hyperphosphorylated tau. The NFT distribution was compared to that of the neuronal cytoskeletal marker SMI32 in these temporal cortical regions. The results showed that the loss of SMI32 immunoreactivity in temporal cortical regions of AD brain is paralleled by an increase in NFTs and AT8 immunoreactivity in neurons. The SMI32 immunoreactivity was drastically reduced in the cortical layers where tangle-bearing neurons are localized. A strong SMI32 immunoreactivity was observed in numerous neurons containing NFTs by double-immunolabeling with SMI32 and AT8. However, few neurons were labeled by AT8 and SMI32. These results suggest that the development of NFTs in some neurons results from some alteration in SMI32 expression, but does not account for all, particularly, early NFT-related changes. Also, there is a clear correlation of NFTs with selective population of pyramidal neurons in the temporal cortical areas and these pyramidal cells are specifically prone to formation of paired helical filaments. Furthermore, these pyramidal neurons might represent a significant portion of the neurons of origin of long corticocortical connection, and consequently contribute to the destruction of memory-related input to the hippocampal formation.

  3. [Exertion syncope disclosing supravalvular mitral stenosis in an infant].

    PubMed

    Buyse, G; Kuchler, H; Crittin, J; Sekarski, N; Hurni, M; Cotting, J; Payot, M

    1993-05-01

    An infant with frequent upper airways infections presented syncopes during meals and weeping since the age of eleven months. Cardiac examination was always normal. At 14 months of age, an echocardiogram with colour Doppler demonstrated a severely stenotic isolated supramitral membrane with severe pulmonary hypertension. The membrane was immediately excised curing the malformation and suppressing definitively the syncopes, probably due to decreased cerebral blood flow during exertion. An echocardiogram should always be performed when syncopes remain unexplained in small children. It allows early diagnosis and treatment of congenital heart defects which do not have auscultatory findings especially those resulting in severe pulmonary venous obstruction.

  4. The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism.

    PubMed

    Gonzalez-Aparicio, Ramiro; Blanco, Eduardo; Serrano, Antonia; Pavon, Francisco Javier; Parsons, Loren H; Maldonado, Rafael; Robledo, Patricia; Fernandez-Espejo, Emilio; de Fonseca, Fernando Rodriguez

    2014-03-01

    Oleoylethanolamide (OEA) is an agonist of the peroxisome proliferator-activated receptor α (PPARα) and has been described to exhibit neuroprotective properties when administered locally in animal models of several neurological disorder models, including stroke and Parkinson's disease. However, there is little information regarding the effectiveness of systemic administration of OEA on Parkinson's disease. In the present study, OEA-mediated neuroprotection has been tested on in vivo and in vitro m