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Sample records for neurons exert temporally

  1. Prucalopride exerts neuroprotection in human enteric neurons.

    PubMed

    Bianco, Francesca; Bonora, Elena; Natarajan, Dipa; Vargiolu, Manuela; Thapar, Nikhil; Torresan, Francesco; Giancola, Fiorella; Boschetti, Elisa; Volta, Umberto; Bazzoli, Franco; Mazzoni, Maurizio; Seri, Marco; Clavenzani, Paolo; Stanghellini, Vincenzo; Sternini, Catia; De Giorgio, Roberto

    2016-05-15

    Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT4 receptors are known to mediate intestinal peristalsis and recent data in experimental animals have shown their role in neuronal maintenance and neurogenesis. This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H2O2 as shown by increased survival (73.5 ± 0.1% of neuronal survival vs. 33.3 ± 0.1%, respectively; P < 0.0001) and a significant reduction of proapoptotic caspase-3 and caspase-9 activation in all neurons tested. The protective effect of prucalopride was reversed by the specific 5-HT4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well-known enterokinetic effect. PMID:26893157

  2. Behavioral Sensitivity of Temporally Modulated Striatal Neurons

    PubMed Central

    Portugal, George S.; Wilson, A. George; Matell, Matthew S.

    2011-01-01

    Recent investigations into the neural mechanisms that underlie temporal perception have revealed that the striatum is an important contributor to interval timing processes, and electrophysiological recording studies have shown that the firing rates of striatal neurons are modulated by the time in a trial at which an operant response is made. However, it remains unclear whether striatal firing rate modulations are related to the passage of time alone (i.e., whether temporal information is represented in an “abstract” manner independent of other attributes of biological importance), or whether this temporal information is embedded within striatal activity related to co-occurring contextual information, such as motor behaviors. This study evaluated these two hypotheses by recording from striatal neurons while rats performed a temporal production task. Rats were trained to respond at different nosepoke apertures for food reward under two simultaneously active reinforcement schedules: a variable-interval (VI-15 s) schedule and a fixed-interval (FI-15 s) schedule of reinforcement. Responding during a trial occurred in a sequential manner composing three phases; VI responding, FI responding, VI responding. The vast majority of task-sensitive striatal neurons (95%) varied their firing rates associated with equivalent behaviors (e.g., periods in which their snout was held within the nosepoke) across these behavioral phases, and 96% of cells varied their firing rates for the same behavior within a phase, thereby demonstrating their sensitivity to time. However, in a direct test of the abstract timing hypothesis, 91% of temporally modulated “hold” cells were further modulated by the overt motor behaviors associated with transitioning between nosepokes. As such, these data are inconsistent with the striatum representing time in an “abstract’ manner, but support the hypothesis that temporal information is embedded within contextual and motor functions of the

  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

    2016-01-01

    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

  5. Temporal correlations in neuronal avalanche occurrence

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

    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.

  6. 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. PMID:19842991

  7. 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

  8. Sensitivity to Temporal Reward Structure in Amygdala Neurons

    PubMed Central

    Bermudez, Maria A.; Göbel, Carl; Schultz, Wolfram

    2012-01-01

    Summary The time of reward and the temporal structure of reward occurrence fundamentally influence behavioral reinforcement and decision processes [1–11]. However, despite knowledge about timing in sensory and motor systems [12–17], we know little about temporal mechanisms of neuronal reward processing. In this experiment, visual stimuli predicted different instantaneous probabilities of reward occurrence that resulted in specific temporal reward structures. Licking behavior demonstrated that the animals had developed expectations for the time of reward that reflected the instantaneous reward probabilities. Neurons in the amygdala, a major component of the brain's reward system [18–29], showed two types of reward signal, both of which were sensitive to the expected time of reward. First, the time courses of anticipatory activity preceding reward delivery followed the specific instantaneous reward probabilities and thus paralleled the temporal reward structures. Second, the magnitudes of responses following reward delivery covaried with the instantaneous reward probabilities, reflecting the influence of temporal reward structures at the moment of reward delivery. In being sensitive to temporal reward structure, the reward signals of amygdala neurons reflected the temporally specific expectations of reward. The data demonstrate an active involvement of amygdala neurons in timing processes that are crucial for reward function. PMID:22959346

  9. 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. PMID:27409809

  10. 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

  11. Flagellar Biosynthesis Exerts Temporal Regulation of Secretion of Specific Campylobacter jejuni Colonization and Virulence Determinants

    PubMed Central

    Barrero-Tobon, Angelica M.; Hendrixson, David R.

    2014-01-01

    Summary 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 virluence 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. PMID:25041103

  12. Temporal Characteristics of Gustatory Responses in Rat Parabrachial Neurons Vary by Stimulus and Chemosensitive Neuron Type

    PubMed Central

    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 500ms 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. PMID:24124597

  13. Temporally tuned neuronal differentiation supports the functional remodeling of a neuronal network in Drosophila.

    PubMed

    Veverytsa, Lyubov; Allan, Douglas W

    2012-03-27

    During insect metamorphosis, neuronal networks undergo extensive remodeling by restructuring their connectivity and recruiting newborn neurons from postembryonic lineages. The neuronal network that directs the essential behavior, ecdysis, generates a distinct behavioral sequence at each developmental transition. Larval ecdysis replaces the cuticle between larval stages, and pupal ecdysis externalizes and expands the head and appendages to their adult position. However, the network changes that support these differences are unknown. Crustacean cardioactive peptide (CCAP) neurons and the peptide hormones they secrete are critical for ecdysis; their targeted ablation alters larval ecdysis progression and results in a failure of pupal ecdysis. In this study, we demonstrate that the CCAP neuron network is remodeled immediately before pupal ecdysis by the emergence of 12 late CCAP neurons. All 12 are CCAP efferents that exit the central nervous system. Importantly, these late CCAP neurons were found to be entirely sufficient for wild-type pupal ecdysis, even after targeted ablation of all other 42 CCAP neurons. Our evidence indicates that late CCAP neurons are derived from early, likely embryonic, lineages. However, they do not differentiate to express their peptide hormone battery, nor do they project an axon via lateral nerve trunks until pupariation, both of which are believed to be critical for the function of CCAP efferent neurons in ecdysis. Further analysis implicated ecdysone signaling via ecdysone receptors A/B1 and the nuclear receptor ftz-f1 as the differentiation trigger. These results demonstrate the utility of temporally tuned neuronal differentiation as a hard-wired developmental mechanism to remodel a neuronal network to generate a scheduled change in behavior. PMID:22393011

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Identifying Temporal Codes in Spontaneously Active Sensory Neurons

    PubMed Central

    Neiman, Alexander B.; Russell, David F.; Rowe, Michael H.

    2011-01-01

    The manner in which information is encoded in neural signals is a major issue in Neuroscience. A common distinction is between rate codes, where information in neural responses is encoded as the number of spikes within a specified time frame (encoding window), and temporal codes, where the position of spikes within the encoding window carries some or all of the information about the stimulus. One test for the existence of a temporal code in neural responses is to add artificial time jitter to each spike in the response, and then assess whether or not information in the response has been degraded. If so, temporal encoding might be inferred, on the assumption that the jitter is small enough to alter the position, but not the number, of spikes within the encoding window. Here, the effects of artificial jitter on various spike train and information metrics were derived analytically, and this theory was validated using data from afferent neurons of the turtle vestibular and paddlefish electrosensory systems, and from model neurons. We demonstrate that the jitter procedure will degrade information content even when coding is known to be entirely by rate. For this and additional reasons, we conclude that the jitter procedure by itself is not sufficient to establish the presence of a temporal code. PMID:22087303

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

    PubMed

    Padival, M A; Blume, S R; Rosenkranz, J A

    2013-08-29

    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

  20. Temporal coding of odor mixtures in an olfactory receptor neuron

    PubMed Central

    Su, Chih-Ying; Martelli, Carlotta; Emonet, Thierry; Carlson, John R.

    2011-01-01

    Most natural odors are mixtures and often elicit percepts distinct from those elicited by their constituents. This emergence of a unique odor quality has long been attributed to central processing. Here we show that sophisticated integration of olfactory information begins in olfactory receptor neurons (ORNs) in Drosophila. Odor mixtures are encoded in the temporal dynamics as well as in the magnitudes of ORN responses. ORNs can respond to an inhibitory odorant with different durations depending on the level of background excitation. ORNs respond to mixtures with distinctive temporal dynamics that reflect the physicochemical properties of the constituent odorants. The insect repellent DEET (N,N-diethyl-m-toluamide), which attenuates odor responses of multiple ORNs, differs from an ORN-specific inhibitor in its effects on temporal dynamics. Our analysis reveals a means by which integration of information from odor mixtures begins in ORNs and provides insight into the contribution of inhibitory stimuli to sensory coding. PMID:21383179

  1. Nitric Oxide Exerts Basal and Insulin-Dependent Anorexigenic Actions in POMC Hypothalamic Neurons.

    PubMed

    Wellhauser, Leigh; Chalmers, Jennifer A; Belsham, Denise D

    2016-04-01

    The arcuate nucleus of the hypothalamus represents a key center for the control of appetite and feeding through the regulation of 2 key neuronal populations, notably agouti-related peptide/neuropeptide Y and proopimelanocortin (POMC)/cocaine- and amphetamine-regulated transcript neurons. Altered regulation of these neuronal networks, in particular the dysfunction of POMC neurons upon high-fat consumption, is a major pathogenic mechanism involved in the development of obesity and type 2 diabetes mellitus. Efforts are underway to preserve the integrity or enhance the functionality of POMC neurons in order to prevent or treat these metabolic diseases. Here, we report for the first time that the nitric oxide (NO(-)) donor, sodium nitroprusside (SNP) mediates anorexigenic actions in both hypothalamic tissue and hypothalamic-derived cell models by mediating the up-regulation of POMC levels. SNP increased POMC mRNA in a dose-dependent manner and enhanced α-melanocortin-secreting hormone production and secretion in mHypoA-POMC/GFP-2 cells. SNP also enhanced insulin-driven POMC expression likely by inhibiting the deacetylase activity of sirtuin 1. Furthermore, SNP enhanced insulin-dependent POMC expression, likely by reducing the transcriptional repression of Foxo1 on the POMC gene. Prolonged SNP exposure prevented the development of insulin resistance. Taken together, the NO(-) donor SNP enhances the anorexigenic potential of POMC neurons by promoting its transcriptional expression independent and in cooperation with insulin. Thus, increasing cellular NO(-) levels represents a hormone-independent method of promoting anorexigenic output from the existing POMC neuronal populations and may be advantageous in the fight against these prevalent disorders. PMID:26930171

  2. 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

  3. Frontal neurons modulate memory retrieval across widely varying temporal scales.

    PubMed

    Zhang, Wen-Hua; Williams, Ziv M

    2015-06-01

    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 prefrontal cortex (VLPFC) of monkeys, an area interconnected with both temporal and frontal associative neocortical regions, signaled the need to alter between retrieval of memories formed at different times. These signals were most closely related to the time interval between initial learning and later retrieval, and did not correlate with task switch demands, novelty, or behavioral response. Consistent with these physiological findings, focal inactivation of the VLPFC led to a marked degradation in retrieval performance. These findings suggest that the VLPFC plays a necessary regulatory role in retrieving memories over different temporal scales. PMID:25979992

  4. 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

  5. Rosiglitazone exerts neuroprotective effects via the suppression of neuronal autophagy and apoptosis in the cortex following traumatic brain injury

    PubMed Central

    YAO, JUNCHAO; ZHENG, KEBIN; ZHANG, XIANG

    2015-01-01

    Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity in adults and children worldwide. Recent studies have demonstrated that both apoptosis and autophagy participate in TBI-induced neuronal cell death and functional loss. The peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist rosiglitazone (RSG) is a well-known anti-inflammatory, which carries out its effects via the activation of PPAR-γ. Previous studies have suggested that RSG may exert neuroprotective effects in animal models of both chronic and acute brain injury; however, whether RSG is involved in autophagic neuronal death following TBI remains to be elucidated. The present study aimed to determine whether RSG carries out its neuroprotective properties via the attenuation of neuronal apoptosis and autophagy, following TBI in a rat model. Furthermore, the role of RSG was investigated with regards to the modulation of inflammation and glutamate excitotoxicity, and the impact of RSG on functional recovery following TBI was determined. The rats were subjected to controlled cortical impact injury, prior to being randomly divided into three groups: A sham-operated group, a TBI group, and an RSG treatment group. The RSG treatment group was intraperitoneally treated with 2 mg/kg RSG immediately after TBI. The results of the present study demonstrated that RSG treatment following TBI significantly reduced neuronal apoptosis and autophagy, and increased functional recovery. These effects were correlated with a decrease in the protein expression levels of tumor necrosis factor α and interleukin-6. However, no significant changes were observed in the protein expression levels of glutamate transporter-1 in the brain cortex. The results of the present study provide in vivo evidence that RSG may exert neuroprotective effects via the inhibition of neuronal apoptosis and autophagy following experimental TBI in rats, and the mechanism underlying these effects may be associated

  6. 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. PMID:22186081

  7. Subthreshold outward currents enhance temporal integration in auditory neurons.

    PubMed

    Svirskis, Gytis; Dodla, Ramana; Rinzel, John

    2003-11-01

    Many auditory neurons possess low-threshold potassium currents ( I(KLT)) that enhance their responsiveness to rapid and coincident inputs. We present recordings from gerbil medial superior olivary (MSO) neurons in vitro and modeling results that illustrate how I(KLT) improves the detection of brief signals, of weak signals in noise, and of the coincidence of signals (as needed for sound localization). We quantify the enhancing effect of I(KLT) on temporal processing with several measures: signal-to-noise ratio (SNR), reverse correlation or spike-triggered averaging of input currents, and interaural time difference (ITD) tuning curves. To characterize how I(KLT), which activates below spike threshold, influences a neuron's voltage rise toward threshold, i.e., how it filters the inputs, we focus first on the response to weak and noisy signals. Cells and models were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the "noise"), together with a larger but still subthreshold postsynaptic conductance, EPSG (the "signal"). Reduction of I(KLT) decreased the SNR, mainly due to an increase in spontaneous firing (more "false positive"). The spike-triggered reverse correlation indicated that I(KLT) shortened the integration time for spike generation. I(KLT) also heightened the model's timing selectivity for coincidence detection of simulated binaural inputs. Further, ITD tuning is shifted in favor of a slope code rather than a place code by precise and rapid inhibition onto MSO cells (Brand et al. 2002). In several ways, low-threshold outward currents are seen to shape integration of weak and strong signals in auditory neurons. PMID:14669013

  8. 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

  9. 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

  10. Hypothalamic oxytocin and vasopressin neurons exert sex-specific effects on pair bonding, gregariousness, and aggression in finches.

    PubMed

    Kelly, Aubrey M; Goodson, James L

    2014-04-22

    Antagonism of oxytocin (OT) receptors (OTRs) impairs the formation of pair bonds in prairie voles (Microtus ochrogaster) and zebra finches (Taenioypygia guttata), and also reduces the preference for the larger of two groups ("gregariousness") in finches. These effects tend to be stronger in females. The contributions of specific peptide cell groups to these processes remain unknown, however. This issue is complicated by the fact that OTRs in finches and voles bind not only forms of OT, but also vasopressin (VP), and >10 cell groups produce each peptide in any given species. Using RNA interference, we found that knockdown of VP and OT production in the paraventricular nucleus of the hypothalamus exerts diverse behavioral effects in zebra finches, most of which are sexually differentiated. Our data show that knockdown of VP production significantly reduces gregariousness in both sexes and exerts sex-specific effects on aggression directed toward opposite-sex birds (increases in males; decreases in females), whereas OT knockdown produces female-specific deficits in gregariousness, pair bonding, and nest cup ownership; reduces side-by-side perching in both sexes; modulates stress coping; and induces hyperphagia in males. These findings demonstrate that paraventricular neurons are major contributors to the effects of VP-OT peptides on pair bonding and gregariousness; reveal previously unknown effects of sex-specific peptide on opposite-sex aggression; and demonstrate a surprising lack of effects on same-sex aggression. Finally, the observed effects of OT knockdown on feeding and stress coping parallel findings in mammals, suggesting that OT modulation of these processes is evolutionarily conserved across the amniote vertebrate classes. PMID:24711411

  11. 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. PMID:27423628

  12. 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

  13. 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. PMID:23266791

  14. 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

  15. Temporal resolution of general odor pulses by olfactory sensory neurons in American cockroaches

    PubMed

    Lemon; Getz

    1997-01-01

    Behavioral and physiological evidence indicates that insect pheromone sensory neurons are able to resolve pulses of pheromone concentration as they occur downwind from a point source, but the abilities of insect sensory neurons that are sensitive to general odors to respond to pulsatile stimuli are unknown. The temporal response characteristics of olfactory sensory neurons of female American cockroaches Periplaneta americana in response to general odors were measured using a series of short odor pulses (20­400 ms). Odor pulses were delivered to olfactory sensilla in a moving airstream controlled by electromagnetic valves. The responses of sensory neurons were recorded using a tungsten electrode placed at the base of the sensillum. The temporal responses of sensory neurons followed the temporal changes in stimulus concentration, which were estimated by replacing the odorant with oil smoke and measuring the concentration of smoke passing through a light beam. Spike frequency varied with odorant concentration with surprisingly fine temporal resolution. Cockroach olfactory sensory neurons were able reliably to follow 25 ms pulses of the pure odorant 1-hexanol and 50 ms pulses of the complex odor blend coconut oil. Lower concentrations of odorants elicited responses with lower peak spike frequencies that still retained the temporal resolution of the stimulus pulses. Thus, responses of olfactory sensory neurons can reflect the fine structures of non-uniform distributions of general odorants in a turbulent odor plume as well as the average odorant concentration. PMID:9319720

  16. Chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy

    PubMed Central

    Fiala, Milan; Avagyan, Hripsime; Merino, Jose Joaquin; Bernas, Michael; Valdivia, Juan; Espinosa-Jeffrey, Araceli; Witte, Marlys; Weinand, Martin

    2012-01-01

    To identify the upstream signals of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy (TLE), we evaluated by immunohistochemistry and confocal microscopy brain tissues of 13 TLE patients and 5 control patients regarding expression of chemokines and cell-cycle proteins. The chemokine RANTES (CCR5) and other CC-chemokines and apoptotic markers (caspase-3, -8, -9) were expressed in lateral temporal cortical and hippocampal neurons of TLE patients, but not in neurons of control cases. The chemokine RANTES is usually found in cytoplasmic and extracellular locations. However, in TLE neurons, RANTES was displayed in an unusual location, the neuronal nuclei. In addition, the cell-cycle regulatory transcription factor E2F1 was found in an abnormal location in neuronal cytoplasm. The pro-inflammatory enzyme cyclooxygenase-2 and cytokine interleukin-1β were expressed both in neurons of patients suffering from temporal lobe epilepsy and from cerebral trauma. The vessels showed fibrin leakage, perivascular macrophages and expression of IL-6 on endothelial cells. In conclusion, the cytoplasmic effects of E2F1 and nuclear effects of RANTES might have novel roles in neuronal apoptosis of TLE neurons and indicate a need to develop new medical and/or surgical neuroprotective strategies against apoptotic signaling by these molecules. Both RANTES and E2F1 signaling are upstream from caspase activation, thus the antagonists of RANTES and/or E2F1 blockade might be neuroprotective for patients with medically intractable temporal lobe epilepsy. The results have implications for the development of new medical and surgical therapies based on inhibition of chemotactic and mitogenic stimuli of neuronal apoptosis in patients with medically intractable temporal lobe epilepsy. PMID:22444245

  17. 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. PMID:9133400

  18. Segment-specific neuronal subtype specification by the integration of anteroposterior and temporal cues.

    PubMed

    Karlsson, Daniel; Baumgardt, Magnus; Thor, Stefan

    2010-05-01

    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

  19. 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

  20. 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. PMID:23401536

  1. 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…

  2. 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

  3. Spatio-temporal pattern recognizers using spiking neurons and spike-timing-dependent plasticity.

    PubMed

    Humble, James; Denham, Susan; Wennekers, Thomas

    2012-01-01

    It has previously been shown that by using spike-timing-dependent plasticity (STDP), neurons can adapt to the beginning of a repeating spatio-temporal firing pattern in their input. In the present work, we demonstrate that this mechanism can be extended to train recognizers for longer spatio-temporal input signals. Using a number of neurons that are mutually connected by plastic synapses and subject to a global winner-takes-all mechanism, chains of neurons can form where each neuron is selective to a different segment of a repeating input pattern, and the neurons are feed-forwardly connected in such a way that both the correct input segment and the firing of the previous neurons are required in order to activate the next neuron in the chain. This is akin to a simple class of finite state automata. We show that nearest-neighbor STDP (where only the pre-synaptic spike most recent to a post-synaptic one is considered) leads to "nearest-neighbor" chains where connections only form between subsequent states in a chain (similar to classic "synfire chains"). In contrast, "all-to-all spike-timing-dependent plasticity" (where all pre- and post-synaptic spike pairs matter) leads to multiple connections that can span several temporal stages in the chain; these connections respect the temporal order of the neurons. It is also demonstrated that previously learnt individual chains can be "stitched together" by repeatedly presenting them in a fixed order. This way longer sequence recognizers can be formed, and potentially also nested structures. Robustness of recognition with respect to speed variations in the input patterns is shown to depend on rise-times of post-synaptic potentials and the membrane noise. It is argued that the memory capacity of the model is high, but could theoretically be increased using sparse codes. PMID:23087641

  4. How Does the Sparse Memory "Engram" Neurons Encode the Memory of a Spatial-Temporal Event?

    PubMed

    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

  5. 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…

  6. 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

  7. Selective vulnerability of hippocampal NAAGergic neurons in experimental temporal lobe epilepsy.

    PubMed

    Pacheco Otalora, Luis F; Moffett, John R; Garrido-Sanabria, Emilio R

    2007-05-01

    The dipeptide N-acetylaspartylglutamate (NAAG) has been recently implicated in numerous neurological disorders. NAAG binds and stimulates group II metabotropic glutamate receptors producing a down-modulation of synaptic glutamate release. In the present immunohistochemical study, we compare the distribution of NAAG-containing (NAAGergic) neurons between the hippocampus of control and chronic epileptic rats obtained with the pilocarpine model of temporal lobe epilepsy. In the hippocampal formation, NAAGergic neurons comprise a subpopulation of GABAergic neurons. Examination by light microscopy revealed a significant reduction of NAAG-immunoreactive neurons in CA3 stratum oriens (35.8%) and CA1 stratum oriens (78.87%), stratum pyramidale (40%), and stratum radiatum (56.6%). Similar loss of NAAGergic neurons was observed in the subiculum characterized by 71.82% and 77.53% reduction in the stratum oriens and radiatum, respectively, when compared with controls. NAAGergic neurons in CA2 and dentate gyrus were apparently resistant to seizure-related cell loss but appeared more complex and exhibited numerous NAAG-positive puncta. Our findings indicate a selective vulnerability of NAAGergic neurons in temporal lobe epilepsy. PMID:17346683

  8. 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. PMID:25355963

  9. Temporally diverse firing patterns in olfactory receptor neurons underlie spatiotemporal neural codes for odors

    PubMed Central

    Raman, Baranidharan; Joseph, Joby; Tang, Jeff; Stopfer, Mark

    2010-01-01

    Odorants are represented as spatiotemporal patterns of spikes in neurons of the antennal lobe (AL, insects) and olfactory bulb (OB, vertebrates). These response patterns have been thought to arise primarily from interactions within the AL/OB, an idea supported, in part, by the assumption that olfactory receptor neurons (ORNs) respond to odorants with simple firing patterns. However, activating the AL directly with simple pulses of current evoked responses in AL neurons that were much less diverse, complex, and enduring than responses elicited by odorants. Similarly, models of the AL driven by simplistic inputs generated relatively simple output. How then are dynamic neural codes for odors generated? Consistent with recent results from several other species, our recordings from locust ORNs showed a great diversity of temporal structure. Further, we found that, viewed as a population, many response features of ORNs were remarkably similar to those observed within the AL. Using a set of computational models constrained by our electrophysiological recordings, we found that the temporal heterogeneity of responses of ORNs critically underlies the generation of spatiotemporal odor codes in the AL. A test then performed in vivo confirmed that, given temporally homogeneous input, the AL cannot create diverse spatiotemporal patterns on its own; however, given temporally heterogeneous input, the AL generated realistic firing patterns. Finally, given the temporally structured input provided by ORNs, we clarified several separate, additional contributions of the AL to olfactory information processing. Thus, our results demonstrate the origin and subsequent reformatting of spatiotemporal neural codes for odors. PMID:20147528

  10. Gray, White Matter Concentration Changes and Their Correlation with Heterotopic Neurons in Temporal Lobe Epilepsy

    PubMed Central

    Tae, Woo Suk; Joo, Eun Yun; Kim, Sung Tae

    2010-01-01

    Objective To identify changes in gray and white matter concentrations (GMC, WMC), and their relation to heterotopic neuron numbers in mesial temporal lobe epilepsy (mTLE). Materials and Methods The gray matter or white matter concentrations of 16 left and 15 right mTLE patients who achieved an excellent surgical outcome were compared with those of 24 healthy volunteers for the left group and with 23 healthy volunteers for the right group, by optimized voxel-based morphometry using unmodulated and modulated images. A histologic count of heterotopic neurons was obtained in the white matter of the anterior temporal lobe originating from the patients' surgical specimens. In addition, the number of heterotopic neurons were tested to determine if there was a correlation with the GMC or WMC. Results The GMCs of the left and right mTLE groups were reduced in the ipsilateral hippocampi, bilateral thalami, precentral gyri, and in the cerebellum. The WMCs were reduced in the ipsilateral white matter of the anterior temporal lobe, bilateral parahippocampal gyri, and internal capsules, but increased in the pons and bilateral precentral gyri. The heterotopic neuron counts in the left mTLE group showed a positive correlation (r = 0.819, p < 0.0001) with GMCs and a negative correlation (r = -0.839, p < 0.0001) with WMCs in the white matter of the anterior temporal lobe. Conclusion The present study shows the abnormalities of the cortico-thalamo-hippocampal network including a gray matter volume reduction in the anterior frontal lobes and an abnormality of brain tissue concentration in the pontine area. Furthermore, heterotopic neuron numbers were significantly correlated with GMC or WMC in the left white matter of anterior temporal lobe. PMID:20046492

  11. 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. PMID:26853282

  12. PTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling.

    PubMed

    Plani-Lam, Janice Hiu-Chor; Chow, Tai-Cheong; Siu, Kam-Leung; Chau, Wing Hin; Ng, Ming-Him James; Bao, Suying; Ng, Cheung Toa; Sham, Pak; Shum, Daisy Kwok-Yan; Ingley, Evan; Jin, Dong-Yan; Song, You-Qiang

    2015-04-01

    Although expression quantitative trait locus, eQTL, serves as an explicit indicator of gene-gene associations, challenges remain to disentangle the mechanisms by which genetic variations alter gene expression. Here we combined eQTL and molecular analyses to identify an association between two seemingly non-associated genes in brain expression data from BXD inbred mice, namely Ptpn21 and Nrg3. Using biotinylated receptor tracking and immunoprecipitation analyses, we determined that PTPN21 de-phosphorylates the upstream receptor tyrosine kinase ErbB4 leading to the up-regulation of its downstream signaling. Conversely, kinase-dead ErbB4 (K751R) or phosphatase-dead PTPN21 (C1108S) mutants impede PTPN21-dependent signaling. Furthermore, PTPN21 also induced Elk-1 activation in embryonic cortical neurons and a novel Elk-1 binding motif was identified in a region located 1919bp upstream of the NRG3 initiation codon. This enables PTPN21 to promote NRG3 expression through Elk-1, which provides a biochemical mechanism for the PTPN21-NRG3 association identified by eQTL. Biologically, PTPN21 positively influences cortical neuronal survival and, similar to Elk-1, it also enhances neuritic length. Our combined approaches show for the first time, a link between NRG3 and PTPN21 within a signaling cascade. This may explain why these two seemingly unrelated genes have previously been identified as risk genes for schizophrenia. PMID:25681686

  13. Neuronal synchrony in relation to burst discharge in epileptic human temporal lobes.

    PubMed

    Colder, B W; Wilson, C L; Frysinger, R C; Chao, L C; Harper, R M; Engel, J

    1996-06-01

    1. Synchronous interactions between neurons in mesial temporal structures of patients with complex partial seizures were studied using cross-correlation analyses. We recorded spontaneous activity from 293 neurons in 24 patients during the interictal state. Patients had depth microelectrodes chronically implanted in amygdala, hippocampal formation, and parahippocampal gyrus to record epileptic activity. One hundred twenty-five cells were recorded from the temporal lobe commonly initiating seizures (ipsilateral temporal lobe), and 168 cells from the contralateral temporal lobe. Eight hundred forty-three cross-correlograms were constructed between all pairs of simultaneously recorded neurons. Cross-correlogram peaks or troughs that exceeded confidence limits within 200 ms of the origin were considered evidence of synchronous neuronal interaction. 2. Synchronous neuronal interactions were observed in 223 of 843 cross-correlograms. Eighty-six percent of these 223 cross-correlograms showed significant central peaks (peak interactions), suggesting excitatory interactions, whereas the remainder displayed significant central troughs (trough interactions), suggesting inhibitory interactions. 3. Cross-correlograms constructed using cells from the ipsilateral temporal lobe (ipsilateral cross-correlograms) were more likely to display significant central troughs (14/262) than cross-correlograms constructed using cells from the contralateral temporal lobe (6/376; contralateral cross-correlograms). Similarly, cross-correlograms constructed using one cell from each hemisphere (11/205; bilateral cross-correlograms) were also more likely to display significant central troughs (trough interactions) than contralateral cross-correlograms. Both ipsilateral (77/262) and contralateral cross-correlograms (102/376) were more likely to display significant central peaks (peak interactions) than bilateral cross-correlograms (13/205). 4. Cells from different structures in the ipsilateral

  14. Different levels of Ih determine distinct temporal integration in bursting and regular-spiking neurons in rat subiculum

    PubMed Central

    van Welie, Ingrid; Remme, Michiel W H; van Hooft, Johannes A; Wadman, Wytse J

    2006-01-01

    Pyramidal neurons in the subiculum typically display either bursting or regular-spiking behaviour. Although this classification into two neuronal classes is well described, it is unknown how these two classes of neurons contribute to the integration of input to the subiculum. Here, we report that bursting neurons posses a hyperpolarization-activated cation current (Ih) that is two-fold larger (conductance, 5.3 ± 0.5 nS) than in regular-spiking neurons (2.2 ± 0.6 nS), whereas Ih exhibits similar voltage-dependent and kinetic properties in both classes of neurons. Bursting and regular-spiking neurons display similar morphology. The difference in Ih between the two classes of neurons is not responsible for the distinct firing patterns, as neither pharmacological blockade of Ih nor enhancement of Ih using a dynamic clamp affects the qualitative firing patterns. Instead, the difference in Ih between bursting and regular-spiking neurons determines the temporal integration of evoked synaptic input from the CA1 area. In response to stimulation at 50 Hz, bursting neurons, with a large Ih, show ∼50% less temporal summation than regular-spiking neurons. The amount of temporal summation in both neuronal classes is equal after pharmacological blockade of Ih. A computer simulation model of a subicular neuron with the properties of either a bursting or a regular-spiking neuron confirmed the pivotal role of Ih in temporal integration of synaptic input. These data suggest that in the subicular network, bursting neurons are better suited to discriminate the content of high-frequency input, such as that occurring during gamma oscillations, than regular-spiking neurons. PMID:16809363

  15. 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.

  16. Balance between Excitation and Inhibition Controls the Temporal Organization of Neuronal Avalanches

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2014-01-01

    SUMMARY Visual information is mediated by two major thalamic pathways, which 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 towards 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. PMID:24698277

  18. 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

  19. A single fraction from Uncaria sinensis exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons.

    PubMed

    Kim, Ha Neui; Jang, Ji Yeon; Choi, Byung Tae

    2015-06-01

    We identified a neuroprotective single fraction among 62 ones of hexane extract from Uncaria sinensis (JGH43IA) and investigated its effects and mechanisms in primary cortical neurons. Pretreatment with JGH43IA showed a significantly increase cell viability in a dose-dependent manner with a decrease in the lactate dehydrogenase release. When we performed morphological assay and flow cytometry to determination of the type of cell death, pretreatment with JGH43IA showed a significant reduction of glutamate-induced apoptotic cell death. Then we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation to elucidate possible pathways of neuroprotection by JGH43IA. Pretreatment with JGH43IA exhibited a significant attenuation of NMDAR GluN2B subunit activation and a decrease in active form of calpain 1 leading to subsequent cleavage of striatal-enriched protein tyrosine phosphatase (STEP). In addition, pretreatment with JGH43IA showed a marked increase of cAMP responsive element binding protein. These results suggest that JGH43IA may have neuroprotective effects through down-regulation of NMDAR GluN2B subunit and calpain 1 activation, and subsequent alleviation of STEP cleavage. This single fraction from U. sinensis might be a useful therapeutic agent for brain disorder associated with glutamate injury. PMID:26140220

  20. A single fraction from Uncaria sinensis exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons

    PubMed Central

    Kim, Ha Neui; Jang, Ji Yeon

    2015-01-01

    We identified a neuroprotective single fraction among 62 ones of hexane extract from Uncaria sinensis (JGH43IA) and investigated its effects and mechanisms in primary cortical neurons. Pretreatment with JGH43IA showed a significantly increase cell viability in a dose-dependent manner with a decrease in the lactate dehydrogenase release. When we performed morphological assay and flow cytometry to determination of the type of cell death, pretreatment with JGH43IA showed a significant reduction of glutamate-induced apoptotic cell death. Then we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation to elucidate possible pathways of neuroprotection by JGH43IA. Pretreatment with JGH43IA exhibited a significant attenuation of NMDAR GluN2B subunit activation and a decrease in active form of calpain 1 leading to subsequent cleavage of striatal-enriched protein tyrosine phosphatase (STEP). In addition, pretreatment with JGH43IA showed a marked increase of cAMP responsive element binding protein. These results suggest that JGH43IA may have neuroprotective effects through down-regulation of NMDAR GluN2B subunit and calpain 1 activation, and subsequent alleviation of STEP cleavage. This single fraction from U. sinensis might be a useful therapeutic agent for brain disorder associated with glutamate injury. PMID:26140220

  1. 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.

  2. 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. PMID:21404332

  3. Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model

    PubMed Central

    Pissadaki, Eleftheria Kyriaki; Sidiropoulou, Kyriaki; Reczko, Martin; Poirazi, Panayiota

    2010-01-01

    The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting, but how these changes affect information processing remains unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal dendritic layers influence the information content of model responses. We find that the temporal delay between activation of the two layers acts as a switch between excitability modes: short delays induce bursting while long delays decrease firing. For long delays, the average firing frequency of the model response discriminates spatially clustered from diffused inputs to the distal dendritic tree. For short delays, the onset latency and inter-spike-interval succession of model responses can accurately classify input signals as temporally close or distant and spatially clustered or diffused across different stimulation protocols. These findings suggest that a CA1 pyramidal neuron may be capable of encoding and transmitting presynaptic spatiotemporal information about the activity of the entorhinal cortex-hippocampal network to higher brain regions via the selective use of either a temporal or a rate code. PMID:21187899

  4. Local and Global Correlations between Neurons in the Middle Temporal Area of Primate Visual Cortex.

    PubMed

    Solomon, Selina S; Chen, Spencer C; Morley, John W; Solomon, Samuel G

    2015-09-01

    In humans and other primates, the analysis of visual motion includes populations of neurons in the middle-temporal (MT) area of visual cortex. Motion analysis will be constrained by the structure of neural correlations in these populations. Here, we use multi-electrode arrays to measure correlations in anesthetized marmoset, a New World monkey where area MT lies exposed on the cortical surface. We measured correlations in the spike count between pairs of neurons and within populations of neurons, for moving dot fields and moving gratings. Correlations were weaker in area MT than in area V1. The magnitude of correlations in area MT diminished with distance between receptive fields, and difference in preferred direction. Correlations during presentation of moving gratings were stronger than those during presentation of moving dot fields, extended further across cortex, and were less dependent on the functional properties of neurons. Analysis of the timescales of correlation suggests presence of 2 mechanisms. A local mechanism, associated with near-synchronous spiking activity, is strongest in nearby neurons with similar direction preference and is independent of visual stimulus. A global mechanism, operating over larger spatial scales and longer timescales, is independent of direction preference and is modulated by the type of visual stimulus presented. PMID:24904074

  5. Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer disease.

    PubMed

    Hu, William T; Josephs, Keith A; Knopman, David S; Boeve, Bradley F; Dickson, Dennis W; Petersen, Ronald C; Parisi, Joseph E

    2008-08-01

    TAR DNA binding protein-43 (TDP-43) immunoreactive neuronal inclusions are detected in 20-30% of Alzheimer disease (AD) brains, but the distribution of this pathology has not been rigorously studied. In this report, we describe region-specific distribution and density of TDP-43 positive neuronal cytoplasmic inclusions (NCIs) in clinically demented individuals with high probability AD pathology, all with Braak neurofibrillary tangle stages of V or VI. Sections of hippocampus, amygdala, as well as temporal, frontal, and parietal neocortex, were analyzed with TDP-43 immunohistochemistry, and the density of NCIs was assessed using a semiquantitative scoring method. Of the 29 cases, six had TDP-43 positive NCIs in the amygdala only and seven had TDP-43 inclusions restricted to amygdala and hippocampus. In 16 cases, TDP-43 immunoreactivity was more widespread, affecting temporal, frontal or parietal neocortex. These findings indicate that medial temporal lobe limbic structures are vulnerable to TDP-43 pathology in advanced AD, and that the amygdala appears to be the most susceptible region. The distribution of the lesions in this cross-sectional analysis may suggest a progression of TDP-43 pathology in AD, with limbic structures in the medial temporal lobe affected first, followed by higher order association cortices. PMID:18592255

  6. Gray matter loss correlates with mesial temporal lobe neuronal hyperexcitability inside the human seizure onset zone

    PubMed Central

    Staba, Richard J.; Ekstrom, Arne D.; Suthana, Nanthia A.; Burggren, Alison; Fried, Itzhak; Engel, Jerome; Bookheimer, Susan Y.

    2011-01-01

    Summary Purpose Patient studies have not provided consistent evidence for interictal neuronal hyperexcitability inside the seizure onset zone (SOZ). We hypothesized that gray matter (GM) loss could have important effects on neuronal firing, and quantifying these effects would reveal significant differences in neuronal firing inside versus outside the SOZ. Methods MRI and computational unfolding of mesial temporal lobe (MTL) subregions was used to construct anatomical maps to compute GM loss in presurgical patients with medically intractable focal seizures in relation to control subjects. In patients, these same maps were used to locate the position of microelectrodes that recorded interictal neuronal activity. Single neuron firing and burst rates were evaluated in relation to GM loss and MTL subregions inside and outside the SOZ. Key findings MTL GM thickness was reduced inside and outside the SOZ in patients with respect to control subjects, yet GM loss was associated more strongly with firing and burst rates in several MTL subregions inside the SOZ. Adjusting single neuron firing and burst rates for the effects of GM loss revealed significantly higher firing rates in the subregion consisting of dentate gyrus and CA2 and CA3 (CA23DG), as well as CA1 and entorhinal cortex (EC) inside versus outside the SOZ where normalized MRI GM loss was ≥1.40 mm. Firing rates were higher in subicular cortex inside the SOZ at GM loss ≥1.97 mm, while burst rates were higher in CA23DG, CA1, and EC inside than outside the SOZ at similar levels of GM loss. Significance The correlation between GM loss and increased firing and burst rates suggests GM structural alterations in MTL subregions are associated with interictal neuronal hyperexcitability inside the SOZ. Significant differences in firing rates and bursting in areas with GM loss inside compared to outside the SOZ indicate that synaptic reorganization following cell loss could be associated with varying degrees of

  7. 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

    2016-01-01

    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

  8. 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

  9. TEMPORAL RESPONSE OF NEURONS TO AMBIENT HEATING IN THE PREOPTIC AND SEPTAL AREA OF THE UNANESTHETIZED RABBIT

    EPA Science Inventory

    The firing rates of single neurons were recorded in the septal and preoptic areas of unanesthetized rabbits during brief periods of ambient heating. The temporal response for neurons responsive to ambient temperature were calculated as the interval of time between the onset of he...

  10. Enhancing Prefrontal Neuron Activity Enables Associative Learning of Temporally Disparate Events.

    PubMed

    Volle, Julien; Yu, Xiaotian; Sun, Huaying; Tanninen, Stephanie E; Insel, Nathan; Takehara-Nishiuchi, Kaori

    2016-06-14

    The ability to link events that are separated in time is important for extracting meaning from experiences and guiding behavior in the future. This ability likely requires the brain to continue representing events even after they have passed, a process that may involve the prefrontal cortex and takes the form of sustained, event-specific neuron activity. Here, we show that experimentally increasing the activity of excitatory neurons in the medial prefrontal cortex (mPFC) enables rats to associate two stimuli separated by a 750-ms long temporal gap. Learning is accompanied by ramping increases in prefrontal theta and beta rhythms during the interval between stimuli. This ramping activity predicts memory-related behavioral responses on a trial-by-trial basis but is not correlated with the same muscular activity during non-memory conditions. Thus, the enhancement of prefrontal neuron excitability extends the time course of evoked prefrontal network activation and facilitates the formation of associations of temporally disparate, but correlated, events. PMID:27264170

  11. 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

  12. Adaptive temporal integration of motion in direction-selective neurons in macaque visual cortex.

    PubMed

    Bair, Wyeth; Movshon, J Anthony

    2004-08-18

    Direction-selective neurons in the primary visual cortex (V1) and the extrastriate motion area MT/V5 constitute a critical channel that links early cortical mechanisms of spatiotemporal integration to downstream signals that underlie motion perception. We studied how temporal integration in direction-selective cells depends on speed, spatial frequency (SF), and contrast using randomly moving sinusoidal gratings and spike-triggered average (STA) analysis. The window of temporal integration revealed by the STAs varied substantially with stimulus parameters, extending farther back in time for slow motion, high SF, and low contrast. At low speeds and high SF, STA peaks were larger, indicating that a single spike often conveyed more information about the stimulus under conditions in which the mean firing rate was very low. The observed trends were similar in V1 and MT and offer a physiological correlate for a large body of psychophysical data on temporal integration. We applied the same visual stimuli to a model of motion detection based on oriented linear filters (a motion energy model) that incorporated an integrate-and-fire mechanism and found that it did not account for the neuronal data. Our results show that cortical motion processing in V1 and in MT is highly nonlinear and stimulus dependent. They cast considerable doubt on the ability of simple oriented filter models to account for the output of direction-selective neurons in a general manner. Finally, they suggest that spike rate tuning functions may miss important aspects of the neural coding of motion for stimulus conditions that evoke low firing rates. PMID:15317857

  13. 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

  14. Temporal filtering properties of ampullary electrosensory neurons in the torus semicircularis of Eigenmannia: evolutionary and computational implications.

    PubMed

    Fortune, E S; Rose, G J

    1997-01-01

    Weakly electric fish have parallel electrosensory systems, the phylogenetically older ampullary system and the novel tuberous system. The tuberous system is an adaptation related to the evolution of active electrolocation. To examine the evolutionary relationship of the ampullary and tuberous systems, the temporal filtering properties of ampullary neurons in the dorsal torus semicircularis of Eigenmannia were studied. 'Whole-cell' recordings were made in vivo using patch-type pipettes. The responses of 19 neurons to sinusoidal electric signals (< 40 Hz) were recorded and the anatomy of these neurons demonstrated by injection of biocytin. All eight low-pass ampullary neurons had broad, relatively smooth post-synaptic potentials (psps) that at low frequencies nicely reflected the sinusoidal stimuli. These neurons had somata of 10-14 microns diameter and thick, spiny dendrites. Eight high-pass neurons were recorded, representing three physiological classes. The first class (3 neurons) had psps that roughly followed the sinusoidal time course of the stimulus; the psp morphology was similar to low-pass neurons. The second class had many small, fast, individual psps; their rate of occurrence varied with the stimulus. Finally, four neurons showed psps that were of constant width across stimulus frequencies. All three classes of high-pass neurons had small somata (8-10 microns diameter) with thin dendrites and either few or no spines. Some of these neurons had large varicosities on the dendrites. Three neurons had band-pass filtering properties: neurons that showed strong band-pass properties were morphologically similar to low-pass neurons. Comparisons of the temporal filtering, shapes of post-synaptic potentials, and anatomy of ampullary and tuberous neurons in the torus suggest that the circuitry for tuberous processing in the torus may have evolved as an elaboration or duplication of the ampullary system. The mechanisms underlying the low-pass filtering characteristics

  15. 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

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

    PubMed

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

    2015-10-01

    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

  17. 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. PMID:26614093

  18. 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. PMID:26945036

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

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

    PubMed

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

    2015-09-01

    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

  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

    2008-07-01

    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. PMID:18511020

  7. Effects of attention and distractor contrast on the responses of middle temporal area neurons to transient motion direction changes.

    PubMed

    Khayat, Paul S; Martinez-Trujillo, Julio C

    2015-06-01

    The ability of primates to detect transient changes in a visual scene can be influenced by the allocation of attention, as well as by the presence of distractors. We investigated the neural substrates of these effects by recording the responses of neurons in the middle temporal area (MT) of two monkeys while they detected a transient motion direction change in a moving target. We found that positioning a distractor near the target impaired the change-detection performance of the animals. This impairment monotonically decreased as the distractor's contrast decreased. A neural correlate of this effect was a decrease in the ability of MT neurons to signal the direction change (detection sensitivity or DS) when a distractor was near the target, both located inside the neuron's receptive field. Moreover, decreasing distractor contrast increased neuronal DS. On the other hand, directing attention away from the target decreased neuronal DS. At the level of individual neurons, we found a negative correlation between the degree of response normalization and the DS. Finally, the intensity of a neuron's response to the change was predictive of the animal's reaction time, suggesting that the activity of our recorded neurons was linked to the animal's detection performance. Our results suggest that the ability of an MT neuron to signal a transient direction change is regulated by the degree of inhibitory drive into the cell. The presence of distractors, their contrast and the allocation of attention influence such inhibitory drive, therefore modulating the ability of the neurons to signal transient changes in stimulus features and consequently behavioral performance. PMID:25885809

  8. Temporal and spatial distribution of Fos protein in the parabrachial nucleus neurons during experimental tooth movement of the rat molar.

    PubMed

    Hiroshima, K; Maeda, T; Hanada, K; Wakisaka, S

    2001-07-27

    The present study was undertaken to reveal spatio-temporal changes in the distribution of Fos-like immunoreactive (-IR) neurons in the parabrachial nucleus (PBN), one of the important relay nuclei for processing autonomic and somatosensory information from the oro-facial regions, following the induction of experimental tooth movement in rat upper molars. The experimental tooth movement was induced by the insertion of elastic rubber between the first and second upper molars. In normal animals, the PBN contained a smaller number of Fos-IR neurons. Following experimental tooth movement, the Fos-IR neurons increased in number significantly on both the ipsilateral and contralateral PBN, reaching a maximum at 4 h (about 10 times that of normal animals), and then decreased gradually. However, a significant number of Fos-IR neurons remained at 24 h post-operation. Remarkable side-by-side differences in the number of Fos-IR neurons were recognized at 1 to 4 h following the experimental tooth movement. Their number returned to normal (basal) levels at 5 days post. All subnuclei of PBN showed similar temporal changes in the number of Fos-IR neurons, this being particularly apparent in lateral PBN. Administrations of morphine (3 and 10 mg/kg, i.p.) drastically reduced the induction of Fos-IR neurons in all subnuclei of both the ipsilateral and contralateral PBN in a dose-dependent manner, and its effect was antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The reduction of Fos-IR neurons by morphine pretreatment suggests that the appearance of Fos-IR neurons in the PBN may be partly due to the noxious stimulation and/or stress arising from tooth movement. The bilateral expression of Fos-IR neurons in the PBN indicates that the experimental tooth movement causes the activation of PBN neurons for the processing of somatosensory as well as autonomic information. The prolonged expression of Fos-IR neurons in all the subnuclei of bilateral PBN reflects clinical features of

  9. Spatial and temporal contrast sensitivity of neurones in areas 17 and 18 of the cat's visual cortex.

    PubMed Central

    Movshon, J A; Thompson, I D; Tolhurst, D J

    1978-01-01

    1. We have examined the spatial and temporal tuning properties of 238 cortical neurones, recorded using conventional techniques from acutely prepared anaesthetized cats. We determined spatial and temporal frequency tuning curves using sinusoidal grating stimuli presented to each neurone's receptive field by a digital computer on a cathode ray tube. 2. We measured tuning curves either by determining response amplitude as a function of spatial or temporal frequency, or by measuring contrast sensitivity (the inverse of the contrast of the grating that just elicited a detectable response). The two measures give very similar tuning curves in all cases. 3. We recorded from 184 neurones in area 17; of these 156 had receptive fields within 5 degrees of the area centralis. The range of preferred spatial frequency for these neurones was 0.3--3 c/deg, and their spatial frequency tuning band widths varied from 0.7 to 3.2 octaves at half-amplitude. The most common band width was roughly 1.3 octaves. Simple and complex cells in area 17 did not differ in their distributions of preferred spatial frequency, although complex cells were, on average, slightly less selective for spatial frequency than simple cells. 4. We recorded from fifty-four neurones from area 18, and performed several experiments in which we recorded from corresponding portions of both area 17 and area 18 in the same electrode penetration. Neurones in area 18 preferred spatial frequencies that were, on average, one third as high as those preferred by area 17 neurones at the same retinal eccentricity. Thus the range of preferred spatial frequency in area eighteen cells having receptive fields within 5 deg of the area centralis was between less than 0.1 and 0.5 c/deg. The distributions of optimum spatial frequency in the two areas were practically non-overlapping at eccentricities as high as 15 deg, the greatest eccentricity we examined. Neurones in area 18 were about as selective for spatial frequency as were

  10. Temporal Structure of Receptor Neuron Input to the Olfactory Bulb Imaged in Behaving Rats

    PubMed Central

    Carey, Ryan M.; Verhagen, Justus V.; Wesson, Daniel W.; Pírez, Nicolás; Wachowiak, Matt

    2009-01-01

    The dynamics of sensory input to the nervous system play a critical role in shaping higher-level processing. In the olfactory system, the dynamics of input from olfactory receptor neurons (ORNs) are poorly characterized and depend on multiple factors, including respiration-driven airflow through the nasal cavity, odorant sorption kinetics, receptor–ligand interactions between odorant and receptor, and the electrophysiological properties of ORNs. Here, we provide a detailed characterization of the temporal organization of ORN input to the mammalian olfactory bulb (OB) during natural respiration, using calcium imaging to monitor ORN input to the OB in awake, head-fixed rats expressing odor-guided behaviors. We report several key findings. First, across a population of homotypic ORNs, each inhalation of odorant evokes a burst of action potentials having a rise time of about 80 ms and a duration of about 100 ms. This rise time indicates a relatively slow, progressive increase in ORN activation as odorant flows through the nasal cavity. Second, the dynamics of ORN input differ among glomeruli and for different odorants and concentrations, but remain reliable across successive inhalations. Third, inhalation alone (in the absence of odorant) evokes ORN input to a significant fraction of OB glomeruli. Finally, high-frequency sniffing of odorant strongly reduces the temporal coupling between ORN inputs and the respiratory cycle. These results suggest that the dynamics of sensory input to the olfactory system may play a role in coding odor information and that, in the awake animal, strategies for processing odor information may change as a function of sampling behavior. PMID:19091924

  11. 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

  12. Temporal encoding precision of bat auditory neurons tuned to target distance deteriorates on the way to the cortex.

    PubMed

    Macías, Silvio; Hechavarría, Julio C; Kössl, Manfred

    2016-03-01

    During echolocation, bats estimate distance to avoid obstacles and capture moving prey. The primary distance cue is the delay between the bat's emitted echolocation pulse and the return of an echo. In the bat's auditory system, echo delay-tuned neurons that only respond to pulse-echo pairs having a specific echo delay serve target distance calculation. Accurate prey localization should benefit from the spike precision in such neurons. Here we show that delay-tuned neurons in the inferior colliculus of the mustached bat respond with higher temporal precision, shorter latency and shorter response duration than those of the auditory cortex. Based on these characteristics, we suggest that collicular neurons are best suited for a fast and accurate response that could lead to fast behavioral reactions while cortical neurons, with coarser temporal precision and longer latencies and response durations could be more appropriate for integrating acoustic information over time. The latter could be important for the formation of biosonar images. PMID:26785850

  13. Temporal coupling between neuronal activity and blood flow in rat cerebellar cortex as indicated by field potential analysis

    PubMed Central

    Mathiesen, Claus; Caesar, Kirsten; Lauritzen, Martin

    2000-01-01

    Laser-Doppler flowmetry and extracellular recordings of field potentials were used to examine the temporal coupling between neuronal activity and increases in cerebellar blood flow (CeBF). Climbing fibre-evoked increases in CeBF were dependent on stimulus duration, indicating that increases in CeBF reflected a time integral in neuronal activity. The simplest way to represent neuronal activity over time was to obtain a running summation of evoked field potential amplitudes (runΣFP). RunΣFP was calculated for each stimulus protocol and compared with the time course of the CeBF responses to demonstrate coupling between nerve cell activity and CeBF. In the climbing fibre system, the amplitude and time course of CeBF were in agreement with the calculated postsynaptic runΣFP (2–20 Hz for 60 s). This suggested coupling between CeBF and neuronal activity in this excitatory, monosynaptic, afferent-input system under these conditions. There was no correlation between runΣFP and CeBF during prolonged stimulation. Parallel fibre-evoked increases in CeBF correlated with runΣFP of pre- and postsynaptic potentials (2–15 Hz for 60 s). At higher stimulation frequencies and during longer-lasting stimulation the time course and amplitudes of CeBF responses correlated with runΣFP of presynaptic, but not postsynaptic potentials. This suggested a more complex relationship in this mixed inhibitory-excitatory, disynaptic, afferent-input system. This study has demonstrated temporal coupling between neuronal activity and CeBF in the monosynaptic, excitatory climbing-fibre system. In the mixed mono- and disynaptic parallel fibre system, temporal coupling was most clearly observed at low stimulation frequencies. We propose that appropriate modelling of electrophysiological data is needed to document functional coupling of neuronal activity and blood flow. PMID:10673558

  14. Voltage-gated Na+ channels enhance the temporal filtering properties of electrosensory neurons in the torus.

    PubMed

    Fortune, Eric S; Rose, Gary J

    2003-08-01

    Regenerative processes enhance postsynaptic potential (PSP) amplitude and behaviorally relevant temporal filtering in more than one-third of electrosensory neurons in the torus semicircularis of Eigenmannia. Data from in vivo current-clamp intracellular recordings indicate that these "regenerative PSPs" can be divided in two groups based on their half-amplitude durations: constant duration (CD) and variable duration (VD) PSPs. CD PSPs have half-amplitude durations of between 20 and 60 ms that do not vary in relation to stimulus periodicity. In contrast, the half-amplitude durations of VD PSPs vary in relation to stimulus periodicity and range from approximately 10 to 500 ms. Injection of 0.1 nA sinusoidal current through the recording electrode demonstrated that CD PSPs and not VD PSPs can be elicited by voltage fluctuations alone. In addition, CD PSPs were blocked by intracellular application of either QX-314 or QX-222, whereas VD PSPs were not. These in vivo data suggest, therefore, that CD PSPs are mediated by voltage-dependent Na+ conductances. PMID:12750421

  15. Temporal coupling between specifications of neuronal and macular fates of the inner ear.

    PubMed

    Deng, Xiaohong; Wu, Doris K

    2016-06-01

    The inner ear is a complex organ comprised of various specialized sensory organs for detecting sound and head movements. The timing of specification for these sensory organs, however, is not clear. Previous fate mapping results of the inner ear indicate that vestibular and auditory ganglia and two of the vestibular sensory organs, the utricular macula (UM) and saccular macula (SM), are lineage related. Based on the medial-lateral relationship where respective auditory and vestibular neuroblasts exit from the otic epithelium and the subsequent formation of the medial SM and lateral UM in these regions, we hypothesized that specification of the two lateral structures, the vestibular ganglion and the UM are coupled and likewise for the two medial structures, the auditory ganglion and the SM. We tested this hypothesis by surgically inverting the primary axes of the otic cup in ovo and investigating the fate of the vestibular neurogenic region, which had been spotted with a lipophilic dye. Our results showed that the laterally-positioned, dye-associated, vestibular ganglion and UM were largely normal in transplanted ears, whereas both auditory ganglion and SM showed abnormalities suggesting the lateral but not the medial-derived structures were mostly specified at the time of transplantation. Both of these results are consistent with a temporal coupling between neuronal and macular fate specifications. PMID:27083418

  16. 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

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

    PubMed

    Raccuglia, Davide; Yan McCurdy, Li; Demir, Mahmut; Gorur-Shandilya, Srinivas; Kunst, Michael; Emonet, Thierry; 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

  18. Analysis and classification of delay-sensitive cortical neurons based on response to temporal parameters in echolocation signals.

    PubMed

    Chittajallu, S K; Palakal, M J; Wong, D

    1995-04-01

    Echolocating bats generate an acoustic image of their target by processing target-reflected echoes of their emitted biosonar pulses. Efforts in building computational models of auditory processing in the bat auditory system, using extensive neurophysiological data from cortical studies are challenged by the intrinsic complexity and the significant variability in neural response to stimuli. In this paper, we use a computerized method for the analysis and classification of delay-sensitive neurons to classify neurons from the auditory cortex of Myotis lucifugus, a species that echolocates with FM signals. The coefficients of the bi-linear fit to the best delay response surfaces (mean R2 = 0.01) were used in classifying the neurons. Six classes were derived that corresponded to the four previously characterized neurophysiologically. The first class corresponded to delay-tuned neurons which exhibited a constant best delay at different pulse repetition rates and pulse durations. Three other classes corresponded to the different subtypes of tracking neurons which changed their best delay to one or both of these stimulus temporal parameters. Two additional classes were differentiated although their best-delay response were similar to either the delay-tuned or the duration and pulse-repetition rate sensitive class. Artificial delay-sensitive neurons built from the parameters of the centroid of each class, will serve a key role in the FM bat auditory system model that we are building. PMID:7642448

  19. Selective neuronal vulnerability of human hippocampal CA1 neurons: lesion evolution, temporal course, and pattern of hippocampal damage in diffusion-weighted MR imaging.

    PubMed

    Bartsch, Thorsten; Döhring, Juliane; Reuter, Sigrid; Finke, Carsten; Rohr, Axel; Brauer, Henriette; Deuschl, Günther; Jansen, Olav

    2015-11-01

    The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n=50), limbic encephalitis (n=30), after status epilepticus (n=17), and transient global amnesia (n=53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus. PMID:26082014

  20. 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

  1. Temporal response dynamics of Drosophila olfactory sensory neurons depends on receptor type and response polarity

    PubMed Central

    Getahun, Merid N.; Wicher, Dieter; Hansson, Bill S.; Olsson, Shannon B.

    2012-01-01

    Insect olfactory sensory neurons (OSN) express a diverse array of receptors from different protein families, i.e. ionotropic receptors (IR), gustatory receptors (GR) and odorant receptors (OR). It is well known that insects are exposed to a plethora of odor molecules that vary widely in both space and time under turbulent natural conditions. In addition to divergent ligand specificities, these different receptors might also provide an increased range of temporal dynamics and sensitivities for the olfactory system. To test this, we challenged different Drosophila OSNs with both varying stimulus durations (10–2000 ms), and repeated stimulus pulses of key ligands at various frequencies (1–10 Hz). Our results show that OR-expressing OSNs responded faster and with higher sensitivity to short stimulations as compared to IR- and Gr21a-expressing OSNs. In addition, OR-expressing OSNs could respond to repeated stimulations of excitatory ligands up to 5 Hz, while IR-expressing OSNs required ~5x longer stimulations and/or higher concentrations to respond to similar stimulus durations and frequencies. Nevertheless, IR-expressing OSNs did not exhibit adaptation to longer stimulations, unlike OR- and Gr21a-OSNs. Both OR- and IR-expressing OSNs were also unable to resolve repeated pulses of inhibitory ligands as fast as excitatory ligands. These differences were independent of the peri-receptor environment in which the receptors were expressed and suggest that the receptor expressed by a given OSN affects both its sensitivity and its response to transient, intermittent chemical stimuli. OR-expressing OSNs are better at resolving low dose, intermittent stimuli, while IR-expressing OSNs respond more accurately to long-lasting odor pulses. This diversity increases the capacity of the insect olfactory system to respond to the diverse spatiotemporal signals in the natural environment. PMID:23162431

  2. 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

  3. 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

  4. Neuromolecular Imaging Shows Temporal Synchrony Patterns between Serotonin and Movement within Neuronal Motor Circuits in the Brain

    PubMed Central

    Broderick, Patricia A.

    2013-01-01

    The present discourse links the electrical and chemical properties of the brain with neurotransmitters and movement behaviors to further elucidate strategies to diagnose and treat brain disease. Neuromolecular imaging (NMI), based on electrochemical principles, is used to detect serotonin in nerve terminals (dorsal and ventral striata) and somatodendrites (ventral tegmentum) of reward/motor mesocorticolimbic and nigrostriatal brain circuits. Neuronal release of serotonin is detected at the same time and in the same animal, freely moving and unrestrained, while open-field behaviors are monitored via infrared photobeams. The purpose is to emphasize the unique ability of NMI and the BRODERICK PROBE® biosensors to empirically image a pattern of temporal synchrony, previously reported, for example, in Aplysia using central pattern generators (CPGs), serotonin and cerebral peptide-2. Temporal synchrony is reviewed within the context of the literature on central pattern generators, neurotransmitters and movement disorders. Specifically, temporal synchrony data are derived from studies on psychostimulant behavior with and without cocaine while at the same time and continuously, serotonin release in motor neurons within basal ganglia, is detected. The results show that temporal synchrony between the neurotransmitter, serotonin and natural movement occurs when the brain is NOT injured via, e.g., trauma, addictive drugs or psychiatric illness. In striking contrast, in the case of serotonin and cocaine-induced psychostimulant behavior, a different form of synchrony and also asynchrony can occur. Thus, the known dysfunctional movement behavior produced by cocaine may well be related to the loss of temporal synchrony, the loss of the ability to match serotonin in brain with motor activity. The empirical study of temporal synchrony patterns in humans and animals may be more relevant to the dynamics of motor circuits and movement behaviors than are studies of static parameters

  5. 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

  6. Theta oscillation and neuronal activity in rat hippocampus are involved in temporal discrimination of time in seconds

    PubMed Central

    Nakazono, Tomoaki; Sano, Tomomi; Takahashi, Susumu; Sakurai, Yoshio

    2015-01-01

    The discovery of time cells revealed that the rodent hippocampus has information regarding time. Previous studies have suggested that the role of hippocampal time cells is to integrate temporally segregated events into a sequence using working memory with time perception. However, it is unclear whether hippocampal cells contribute to time perception itself because most previous studies employed delayed matching-to-sample tasks that did not separately evaluate time perception from working memory processes. Here, we investigated the function of the rat hippocampus in time perception using a temporal discrimination task. In the task, rats had to discriminate between durations of 1 and 3 s to get a reward, and maintaining task-related information as working memory was not required. We found that some hippocampal neurons showed firing rate modulation similar to that of time cells. Moreover, theta oscillation of local field potentials (LFPs) showed a transient enhancement of power during time discrimination periods. However, there were little relationships between the neuronal activities and theta oscillations. These results suggest that both the individual neuronal activities and theta oscillations of LFPs in the hippocampus have a possibility to be engaged in seconds order time perception; however, they participate in different ways. PMID:26157367

  7. 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. PMID:26462572

  8. Firing patterns of human limbic neurons during stereoencephalography (SEEG) and clinical temporal lobe seizures.

    PubMed

    Babb, T L; Wilson, C L; Isokawa-Akesson, M

    1987-06-01

    Comparisons of the patterns of neuronal firing and stereoencephalography (SEEG) recorded from the same microelectrodes chronically implanted in the human limbic system were made in order to study neuronal electrogenesis at onset and during propagation of focal partial complex seizures. Alert or sleeping patients were monitored during spontaneous subclinical seizures (no alterations in consciousness detectable), during auras reported by the patients as typical, and during clinical seizures with loss of consciousness, movements and post-ictal confusion. During subclinical SEEG seizures (ipsilateral, normal consciousness), few neurons increased firing (estimated at only 7%) either at the focus or at propagated sites. During auras, with altered consciousness, there were relatively few neurons that increased firing, with the estimate about 14% or twice as many as during a subclinical seizure. During the onset of a clinical seizure that involved loss of consciousness, movements and post-ictal confusion, many neurons were recruited into increased firing, with an estimate of approximately 36%. During this increased electrogenesis, neurons fired briefly in association with high-frequency local SEEG; however, the bursts were shorter than the SEEG seizure pattern. Apparently, other local neurons were recruited to fire in bursts to sustain sufficient axonal driving for widespread propagation of the seizure. When the focal SEEG slowed, the units stopped firing, which suggested that the 'focal' seizure need not be sustained for more than several seconds because propagated seizure activity was self-sustaining at distant structures. The data lead to the conclusion that SEEG seizures can be generated focally by synchronous firing of fewer than 10% of neurons in the 'epileptic pool.' However, when greater percentages of neurons are recruited in the 'epileptic focus' there is greater propagation to widespread sites, especially contralaterally, which will produce clinical partial

  9. Cortical integration in the visual system of the macaque monkey: large-scale morphological differences in the pyramidal neurons in the occipital, parietal and temporal lobes.

    PubMed Central

    Elston, G N; Tweedale, R; Rosa, M G

    1999-01-01

    Layer III pyramidal neurons were injected with Lucifer yellow in tangential cortical slices taken from the inferior temporal cortex (area TE) and the superior temporal polysensory (STP) area of the macaque monkey. Basal dendritic field areas of layer III pyramidal neurons in area STP are significantly larger, and their dendritic arborizations more complex, than those of cells in area TE. Moreover, the dendritic fields of layer III pyramidal neurons in both STP and TE are many times larger and more complex than those in areas forming 'lower' stages in cortical visual processing, such as the first (V1), second (V2), fourth (V4) and middle temporal (MT) visual areas. By combining data on spine density with those of Sholl analyses, we were able to estimate the average number of spines in the basal dendritic field of layer III pyramidal neurons in each area. These calculations revealed a 13-fold difference in the number of spines in the basal dendritic field between areas STP and V1 in animals of similar age. The large differences in complexity of the same kind of neuron in different visual areas go against arguments for isopotentiality of different cortical regions and provide a basis that allows pyramidal neurons in temporal areas TE and STP to integrate more inputs than neurons in more caudal visual areas. PMID:10445291

  10. Sustained firing of model central auditory neurons yields a discriminative spectro-temporal representation for natural sounds.

    PubMed

    Carlin, Michael A; Elhilali, Mounya

    2013-01-01

    The processing characteristics of neurons in the central auditory system are directly shaped by and reflect the statistics of natural acoustic environments, but the principles that govern the relationship between natural sound ensembles and observed responses in neurophysiological studies remain unclear. In particular, accumulating evidence suggests the presence of a code based on sustained neural firing rates, where central auditory neurons exhibit strong, persistent responses to their preferred stimuli. Such a strategy can indicate the presence of ongoing sounds, is involved in parsing complex auditory scenes, and may play a role in matching neural dynamics to varying time scales in acoustic signals. In this paper, we describe a computational framework for exploring the influence of a code based on sustained firing rates on the shape of the spectro-temporal receptive field (STRF), a linear kernel that maps a spectro-temporal acoustic stimulus to the instantaneous firing rate of a central auditory neuron. We demonstrate the emergence of richly structured STRFs that capture the structure of natural sounds over a wide range of timescales, and show how the emergent ensembles resemble those commonly reported in physiological studies. Furthermore, we compare ensembles that optimize a sustained firing code with one that optimizes a sparse code, another widely considered coding strategy, and suggest how the resulting population responses are not mutually exclusive. Finally, we demonstrate how the emergent ensembles contour the high-energy spectro-temporal modulations of natural sounds, forming a discriminative representation that captures the full range of modulation statistics that characterize natural sound ensembles. These findings have direct implications for our understanding of how sensory systems encode the informative components of natural stimuli and potentially facilitate multi-sensory integration. PMID:23555217

  11. Hierarchical Temporal Memory Based on Spin-Neurons and Resistive Memory for Energy-Efficient Brain-Inspired Computing.

    PubMed

    Fan, Deliang; Sharad, Mrigank; Sengupta, Abhronil; Roy, Kaushik

    2016-09-01

    Hierarchical temporal memory (HTM) tries to mimic the computing in cerebral neocortex. It identifies spatial and temporal patterns in the input for making inferences. This may require a large number of computationally expensive tasks, such as dot product evaluations. Nanodevices that can provide direct mapping for such primitives are of great interest. In this paper, we propose that the computing blocks for HTM can be mapped using low-voltage, magnetometallic spin-neurons combined with an emerging resistive crossbar network, which involves a comprehensive design at algorithm, architecture, circuit, and device levels. Simulation results show the possibility of more than 200× lower energy as compared with a 45-nm CMOS ASIC design. PMID:26285225

  12. 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. PMID:22430497

  13. 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. PMID:25764308

  14. Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish.

    PubMed

    Montgomery, Jacob E; Wiggin, Timothy D; Rivera-Perez, Luis M; Lillesaar, Christina; Masino, Mark A

    2016-06-01

    Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have been examined in detail at different ages; however, some aspects of the development of these cells remain unclear. Although antibodies to serotonin (5-HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults, the only tryptophan hydroxylase (tph) transcript that has been described in the spinal cord is tph1a. Paradoxically, spinal tph1a is only expressed transiently in embryos, which brings the source of 5-HT in the ISNs of larvae and adults into question. Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish larvae. We confirmed this hypothesis through in situ hybridization. Next, we used 5-HT antibody labeling and transgenic markers of tph2-expressing neurons to identify a transient population of ISNs in embryos that was distinct from ISNs that appeared later in development. The existence of separate ISN populations may not have been recognized previously due to their shared location in the ventral spinal cord. Finally, we used transgenic markers and immunohistochemical labeling to identify the transient ISN population as GABAergic Kolmer-Agduhr double-prime (KA″) neurons. Altogether, this study revealed a novel developmental paradigm in which KA″ neurons are transiently serotonergic before the appearance of a stable population of tph2-expressing ISNs. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 673-687, 2016. PMID:26437856

  15. Temporal Rac1 - HIF-1 crosstalk modulates hypoxic survival of aged neurons.

    PubMed

    Güntert, Tanja; Gassmann, Max; Ogunshola, Omolara O

    2016-07-01

    Neurodegenerative diseases are frequently associated with hypoxic conditions. During hypoxia the neuronal cytoskeleton is rapidly reorganized and such abnormalities are directly linked to adverse outcomes. Besides their roles as master regulators of the cytoskeleton, the Rho GTPases are also involved in cellular processes stimulated by hypoxic stress. We investigated the contribution of Rac1-mediated signaling to hypoxic responses of mature neurons using primary cortical cells cultured for 17 days in vitro. We show Rac1 is both upregulated and activated during hypoxia. Pharmacological inhibition of Rac1, but not RhoA, completely abrogated hypoxic HIF-1α stabilization and expression of the HIF-1 targets VEGF and GLUT1. Furthermore activity of JNK and GSK3β were also highly dependent on Rac1 activity and biphasic effects were observed after 6 and 24h of exposure. Notably, inhibition of either pathway suppressed HIF-1α accumulation. Although inhibition of Rac1 did not affect neuronal viability during acute exposure cell death was strongly induced after 24h revealing a time-dependent effect of Rac1 signaling on survival. Thus hypoxia-activated Rac1 is critical for neuronal HIF-1α stabilization and survival during oxygen deprivation via integration of complex signaling cascades. PMID:27018294

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

    PubMed Central

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

    2008-01-01

    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 100Hz, 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. PMID:18539336

  17. Temporal resolution of neurons in cat inferior colliculus to intracochlear electrical stimulation: effects of neonatal deafening and chronic stimulation.

    PubMed

    Snyder, R; Leake, P; Rebscher, S; Beitel, R

    1995-02-01

    1. Cochlear implants have been available for > 20 yr to profoundly deaf adults who have lost their hearing after acquiring language. The success of these cochlear prostheses has encouraged the application of implants in prelingually deaf children as young as 2 yr old. To further characterize the consequences of chronic intracochlear electrical stimulation (ICES) on the developing auditory system, the temporal-response properties of single neurons in the inferior colliculus (IC) were recorded in deafened anesthetized cats. 2. The neurons were excited by unilateral ICES with the use of a scala tympani stimulating electrode implanted in the left cochlea. The electrodes were modeled after those used in cochlear implant patients. Responses of 443 units were recorded extracellularly in the contralateral (right) IC with the use of tungsten microelectrodes. Recordings were made in three groups of adult animals: neonatally deafened/chronically stimulated animals (192 units), neonatally deafened/unstimulated animals (80 units), and adult-deafened/prior normal-hearing animals (171 units). The neonatally deafened cats were deafened by multiple intramuscular injections of neomycin sulfate and never developed demonstrable hearing. Most of the deafened, chronically stimulated animals were implanted at 6 wk of age and stimulated at suprathreshold levels for 4 h/day for 3-6 mo. The unstimulated animals were implanted as adults at least 2 wk before the acute physiological experiment and were left unstimulated until the acute experiment was conducted. Prior-normal adults were deafened and implanted at least 2 wk before the acute experiment. 3. IC units were isolated with the use of a search stimulus consisting of three cycles of a 100-Hz sinusoid. Most units responded to sinusoidal stimulation with either an onset response or a sustained response. Onset units were the predominant unit found in the external nucleus, whereas sustained units were found almost exclusively in the central

  18. 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…

  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. Rapid feedforward computation by temporal encoding and learning with spiking neurons.

    PubMed

    Yu, Qiang; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

    2013-10-01

    Primates perform remarkably well in cognitive tasks such as pattern recognition. Motivated by recent findings in biological systems, a unified and consistent feedforward system network with a proper encoding scheme and supervised temporal rules is built for solving the pattern recognition task. The temporal rules used for processing precise spiking patterns have recently emerged as ways of emulating the brain's computation from its anatomy and physiology. Most of these rules could be used for recognizing different spatiotemporal patterns. However, there arises the question of whether these temporal rules could be used to recognize real-world stimuli such as images. Furthermore, how the information is represented in the brain still remains unclear. To tackle these problems, a proper encoding method and a unified computational model with consistent and efficient learning rule are proposed. Through encoding, external stimuli are converted into sparse representations, which also have properties of invariance. These temporal patterns are then learned through biologically derived algorithms in the learning layer, followed by the final decision presented through the readout layer. The performance of the model with images of digits from the MNIST database is presented. The results show that the proposed model is capable of recognizing images correctly with a performance comparable to that of current benchmark algorithms. The results also suggest a plausibility proof for a class of feedforward models of rapid and robust recognition in the brain. PMID:24808592

  1. 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…

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

    PubMed

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

    2011-09-01

    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 (V(m) 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

  3. Elevated serum neuron-specific enolase in patients with temporal lobe epilepsy: a video-EEG study.

    PubMed

    Palmio, Johanna; Keränen, Tapani; Alapirtti, Tiina; Hulkkonen, Janne; Mäkinen, Riikka; Holm, Päivi; Suhonen, Jaana; Peltola, Jukka

    2008-10-01

    Established markers of brain damage, neuron-specific enolase (NSE) and S-100b protein (S-100), may increase after status epilepticus, but whether a single tonic-clonic or complex partial seizure induces elevation of these markers is not known. Furthermore, it is unclear whether the risk of seizure-related neuronal damage in temporal lobe epilepsy (TLE) differs from that in extratemporal lobe epilepsies (XTLE). The aim of this study was to analyze NSE and S-100 in patients with TLE and XTLE after acute seizures. The levels of NSE and S-100 were measured in serum before (0h) and at 3, 6, 12, and 24h after acute seizures in 31 patients during inpatient video-EEG monitoring. The patients were categorized into the TLE and the XTLE group based on video-EEG recordings and MRI findings. Fifteen patients had TLE and 16 XTLE. Index seizures were mainly complex partial seizures (n=21). In TLE mean+/-S.D. values for NSE levels (mug/L) were 8.36+/-2.64 (0h), 11.35+/-3.84 (3h), 13.48+/-4.49 (6h), 12.95+/-5.46 (12h) and 10.33+/-3.13 (24h) (p=0.006, ANOVA). In XTLE the changes were not significant (p=0.3). There was less increase in the levels of S-100 in TLE (p=0.05) and no significant change in XTLE (p=0.4). The levels of markers of neuronal damage were increased in patients with TLE, not only after tonic-clonic but also after complex partial seizures. These data suggest that TLE may be associated with brain damage. PMID:18595663

  4. 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

  5. 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

  6. The influence of temporal pattern of stimulation on delay tuning of neurons in the auditory cortex of the FM bat, Myotis lucifugus.

    PubMed

    Tanaka, H; Wong, D

    1993-03-01

    In echolocating bats, delay-sensitive neurons show facilitative responses to simulated pulse-echo pairs at particular echo delays. Three experiments examined how the temporal pattern of stimulation affected the delay tuning of neurons in the auditory cortex of the awake FM bat, Myotis lucifugus. First, delay tuning was compared using a series of pulse-echo pairs fixed in echo delay ('standard' stimuli), and a series of pulse-echo pairs in which successive sound pairs decreased by a fixed echo-delay step ('approach' stimuli). Similar best delays were measured with both stimulation patterns presented at repetition rates in which the neuron was delay-sensitive. At the higher delay-sensitive pulse repetition rates, approach stimuli evoked larger delay-dependent responses. Second, approach stimuli were fixed at different intertrial intervals. The best delay was unaffected by intertrial interval, although some neurons showed larger responses for longer intertrial intervals (0.5, 1.0 s), especially at the higher delay-sensitive pulse repetition rates. Third, approach stimuli were fixed at different echo-delay steps to simulate target velocity. The majority of neurons showed some sensitivity to echo-delay step, with clear preference for target velocity mainly between 1.8-7.0 m/s. This suggests that delay-sensitive neurons compute target velocity by rate of change of echo delay over successive echoes. Thus, response properties of cortical neurons are influenced by dynamic acoustic conditions found in target-directed flight. PMID:8473246

  7. 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

  8. 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

  9. 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.

  10. Preliminary findings suggest the number and volume of supragranular and infragranular pyramidal neurons are similar in the anterior superior temporal area of control subjects and subjects with autism

    PubMed Central

    Kim, Esther; Camacho, Jasmin; Combs, Zachary; Ariza, Jeanelle; Lechpammer, Mirna; Noctor, Stephen; Martínez-Cerdeño, Verónica

    2015-01-01

    We investigated the cytoarchitecture of the anterior superior temporal area (TA2) of the postmortem cerebral cortex in 9 subjects with autism and 9 age-matched typically developing subjects between the ages of 13 and 56 years. The superior temporal gyrus is involved in auditory processing and social cognition and its pathology has been correlated with autism. We quantified the number and soma volume of pyramidal neurons in the supragranular layers and pyramidal neurons in the infragranular layers in each subject. We did not find significant differences in the number or volume of supragranular or infragranular neurons in the cerebral cortex of subjects with autism compared to typically developing subjects. This report does not support an alteration of supragranular to infragranular neurons in autism. However, further stereological analysis of the number of cells and cell volumes in specific cortical areas is needed to better establish the cellular phenotype of the autistic cerebral cortex and to understand its clinical relevance in autism. PMID:25582788

  11. 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

  12. A Million-Plus Neuron Model of the Hippocampal Dentate Gyrus: Dependency of Spatio-Temporal Network Dynamics on Topography

    PubMed Central

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

    2016-01-01

    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. PMID:26737346

  13. 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. PMID:26737346

  14. [Chronic exertional compartment syndrome].

    PubMed

    Rom, Eyal; Tenenbaum, Shay; Chechick, Ofir; Burstein, Gideon; Amit, Yehuda; Thein, Ran

    2013-10-01

    Chronic exertional compartment syndrome is an uncommon phenomenon first reported in the mid 50's. This condition is characterized by sharp pain during physical activity, causing reduction in activity frequency or intensity and even abstention. This syndrome is caused by elevation of the intra-compartmental pressure which leads to decreased tissue perfusion, thus ischemic damage to the tissue ensues. Chronic exertional syndrome is usually related to repetitive physical activity, usually in young people and athletes. The physical activity performed by the patient causes a rise in intra-compartmental pressure and thereby causes pain. The patient discontinues the activity and the pain subsides within minutes of rest. Chronic exertional syndrome is reported to occur in the thigh, shoulder, arm, hand, foot and gluteal region, but most commonly in the leg, especially the anterior compartment. The diagnosis of chronic exertional syndrome is primarily based on patients' medical history, supported by intramuscular pressure measurement of the specific compartment involved. Treatment of chronic exertional syndrome, especially the anterior and lateral compartment of the leg is mainly by surgery i.e. fasciotomy. If the patient is reluctant to undergo a surgical procedure, the conservative treatment is based on abstention from the offending activity, changing footwear or using arch support. However, the conservative approach is not as successful as surgical treatment. PMID:24450036

  15. 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

  16. Exertional Leg Pain.

    PubMed

    Rajasekaran, Sathish; Finnoff, Jonathan T

    2016-02-01

    Exertional leg pain is a common condition seen in runners and the general population. Given the broad differential diagnosis of this complaint, this article focuses on the incidence, anatomy, pathophysiology, clinical presentation, diagnostic evaluation, and management of common causes that include medial tibial stress syndrome, tibial bone stress injury, chronic exertional compartment syndrome, arterial endofibrosis, popliteal artery entrapment syndrome, and entrapment of the common peroneal, superficial peroneal, and saphenous nerves. Successful diagnosis of these conditions hinges on performing a thorough history and physical examination followed by proper diagnostic testing and appropriate management. PMID:26616179

  17. Temporal Resolution of Misfolded Prion Protein Transport, Accumulation, Glial Activation, and Neuronal Death in the Retinas of Mice Inoculated with Scrapie.

    PubMed

    West Greenlee, M Heather; Lind, Melissa; Kokemuller, Robyn; Mammadova, Najiba; Kondru, Naveen; Manne, Sireesha; Smith, Jodi; Kanthasamy, Anumantha; Greenlee, Justin

    2016-09-01

    Currently, there is a lack of pathological landmarks to describe the progression of prion disease in vivo. Our goal was to use an experimental model to determine the temporal relationship between the transport of misfolded prion protein (PrP(Sc)) from the brain to the retina, the accumulation of PrP(Sc) in the retina, the response of the surrounding retinal tissue, and loss of neurons. Retinal samples from mice inoculated with RML scrapie were collected at 30, 60, 90, 105, and 120 days post inoculation (dpi) or at the onset of clinical signs of disease (153 dpi). Retinal homogenates were tested for prion seeding activity. Antibody staining was used to assess accumulation of PrP(Sc) and the resulting response of retinal tissue. Loss of photoreceptors was used as a measure of neuronal death. PrP(Sc) seeding activity was first detected in all samples at 60 dpi. Accumulation of PrP(Sc) and coincident activation of retinal glia were first detected at 90 dpi. Activation of microglia was first detected at 105 dpi, but neuronal death was not detectable until 120 dpi. Our results demonstrate that by using the retina we can resolve the temporal separation between several key events in the pathogenesis of prion disease. PMID:27521336

  18. The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures.

    PubMed

    Wong, Shi-Bing; Hung, Wei-Chen; Min, Ming-Yuan

    2016-06-30

    Tian ma (Gastrodia elata, GE) is an ancient Chinese herbal medicine that has been suggested to be effective as an anticonvulsant and analgesic, and to have sedative effects against vertigo, general paralysis, epilepsy and tetanus. The primary active ingredient isolated from GE is termed gastrodin, which is the glucoside of 4-hydroxybenzyl alcohol (4-HBA). Gastrodin can abolish hypoxia-, glutamate- and N-methyl-D-aspartate (NMDA) receptor-induced toxicity in primary culture of rat cortical neurons, and reduces seizure severity in seizure-sensitive gerbils. We evaluated the effect of gastrodin on NMDA excitotoxicity in hippocampal slice cultures (HSCs) with propidium iodide (PI) fluorescence measurement. We also evaluated the effects of gastrodin for treating active in vivo temporal lobe seizures induced by lithium/pilocarpine. Seizure severity, time span to seizure onset, mortality rate and hippocampal histology for survivors were compared. The effect of gastrodin was evaluated for treating in vitro seizures induced by Mg²⁺-free medium in hippocampal slices. Frequencies and amplitudes of epileptiform discharges were compared. The effect of gastrodin on synaptic transmission was evaluated on hippocampal CA1 Schaffer collaterals. Application of 25 μM gastrodin significantly suppressed NMDA excitotoxicity in CA3 but not in CA1 hippocampus and dentate gyrus. Intraventricular gastrodin accelerated seizure onset for 12 min after intraperitoneal pilocarpine injection (P = 0.051). Three of five rats (60%) in the gastrodin group, and three of four (75%) in the dimethyl sulfoxide (DMSO) group died within 3 days after status epilepticus (SE). Gastrodin also failed to inhibit epileptiform discharges in hippocampal slices induced by Mg²⁺-free medium, believed to be NMDA receptor-mediated spontaneous activity. The frequencies of the spontaneous epileptiform discharges were similar under treatments with 25 μM gastrodin, 200 μM gastrodin and DMSO. For the evaluation of

  19. 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

  20. Early Mechanisms of Pathobiology Are Revealed by Transcriptional Temporal Dynamics in Hippocampal CA1 Neurons of Prion Infected Mice

    PubMed Central

    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

  1. 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. PMID:27013413

  2. Chronic exertional compartment syndrome.

    PubMed

    George, Christopher A; Hutchinson, Mark R

    2012-04-01

    Chronic exertional compartment syndrome is a relatively common, but often overlooked cause of leg pain in athletes. A careful history and physical examination is essential in the diagnosis of CECS. Affected individuals have recurrent, activity-related leg pain that recurs at a consistent duration or intensity and is only relieved by rest. Measurement of baseline and postexercise compartment pressures confirms the diagnosis and helps in the planning of treatment. Surgical treatment with fasciotomy of the involved compartments is successful in allowing patients to return to full activity levels. With surgical treatment, it is critical to address all affected compartments as well as releasing any fascial defects, both of which may cause recurrent symptoms if neglected. With appropriate diagnosis and treatment, excellent outcomes can be achieved and allow athletes to return to full, unrestricted activity levels. PMID:22341019

  3. 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. PMID:25857536

  4. Temporally advanced dynamic change of receptive field of lateral geniculate neurons during brief visual stimulation: Effects of brainstem peribrachial stimulation.

    PubMed

    Jurkus, P; Ruksenas, O; Heggelund, P

    2013-07-01

    Processing of visual information in the brain seems to proceed from initial fast but coarse to subsequent detailed processing. Such coarse-to-fine changes appear also in the response of single neurons in the visual pathway. In the dorsal lateral geniculate nucleus (dLGN), there is a dynamic change in the receptive field (RF) properties of neurons during visual stimulation. During a stimulus flash centered on the RF, the width of the RF-center, presumably related to spatial resolution, changes rapidly from large to small in an initial transient response component. In a subsequent sustained component, the RF-center width is rather stable apart from an initial slight widening. Several brainstem nuclei modulate the geniculocortical transmission in a state-dependent manner. Thus, modulatory input from cholinergic neurons in the peribrachial brainstem region (PBR) enhances the geniculocortical transmission during arousal. We studied whether such input also influences the dynamic RF-changes during visual stimulation. We compared dynamic changes of RF-center width of dLGN neurons during brief stimulus presentation in a control condition, with changes during combined presentation of the visual stimulus and electrical PBR-stimulation. The major finding was that PBR-stimulation gave an advancement of the dynamic change of the RF-center width such that the different response components occurred earlier. Consistent with previous studies, we also found that PBR-stimulation increased the gain of firing rate during the sustained response component. However, this increase of gain was particularly strong in the transition from the transient to the sustained component at the time when the center width was minimal. The results suggest that increased modulatory PBR-input not only increase the gain of the geniculocortical transmission, but also contributes to faster dynamics of transmission. We discuss implications for possible effects on visual spatial resolution. PMID:23542736

  5. Ginsenoside Rg1 exerts a protective effect against Aβ₂₅₋₃₅-induced toxicity in primary cultured rat cortical neurons through the NF-κB/NO pathway.

    PubMed

    Wu, Jiaying; Yang, Hongyu; Zhao, Qingwei; Zhang, Xingguo; Lou, Yijia

    2016-03-01

    Ginsenoside Rg1 (Rg1) is a multipotent triterpene saponin extracted from ginseng, and has been proven to act as a nootropic agent against various types of neurological damage. The present study was designed to investigate the neuroprotective effect and the underlying mechanisms of Rg1 on apoptosis induced by β-amyloid peptide 25-35 (Aβ25-35) in primary cultured cortical neurons. The primary neurons were preincubated with 20 µM Rg1 for 24 h and exposed to 10 µM Aβ25-35 for 72 h. In the present study, we found that Rg1 prevented nuclear factor κ-light-chain‑enhancer of activated B cells (NF-κB) nuclear translocation and IκB-α phosphorylation in primary cultured cortical neurons after Aβ25-35 exposure by scavenging excess reactive oxygen species (ROS); ROS was measured using DCFDA and examined using a fluorescence microscope. In addition, Rg1 successfully suppressed Aβ25‑35-inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in a NF-κB-dependent manner; the suppression of NO was clearly illustrated by the NO production assay. Pretreatment of the cells with Rg1 elevated the proportion of Bcl-2/Bax, lessened the release of cytochrome c from mitochondria into cytoplasm and then blocked mitochondrial apoptotic cascades after Aβ25-35 insult by lowering NO generation. Taken together, our data demonstrate that Rg1 rescues primary cultured cortical neurons from Aβ25-35-induced cell apoptosis through the downregulation of the NF-κB/NO signaling pathway. PMID:26865401

  6. Temporal target restriction of olfactory receptor neurons by Semaphorin-1a/PlexinA-mediated axon-axon interactions.

    PubMed

    Sweeney, Lora B; Couto, Africa; Chou, Ya-Hui; Berdnik, Daniela; Dickson, Barry J; Luo, Liqun; Komiyama, Takaki

    2007-01-18

    Axon-axon interactions have been implicated in neural circuit assembly, but the underlying mechanisms are poorly understood. Here, we show that in the Drosophila antennal lobe, early-arriving axons of olfactory receptor neurons (ORNs) from the antenna are required for the proper targeting of late-arriving ORN axons from the maxillary palp (MP). Semaphorin-1a is required for targeting of all MP but only half of the antennal ORN classes examined. Sema-1a acts nonautonomously to control ORN axon-axon interactions, in contrast to its cell-autonomous function in olfactory projection neurons. Phenotypic and genetic interaction analyses implicate PlexinA as the Sema-1a receptor in ORN targeting. Sema-1a on antennal ORN axons is required for correct targeting of MP axons within the antennal lobe, while interactions amongst MP axons facilitate their entry into the antennal lobe. We propose that Sema-1a/PlexinA-mediated repulsion provides a mechanism by which early-arriving ORN axons constrain the target choices of late-arriving axons. PMID:17224402

  7. 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

  8. 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

  9. Temporally structured impulse activity in spontaneously discharging somatosensory cortical neurons in the awake cat: recognition and quantitative description of four different patterns of bursts, post-recording GFAP immunohistology and computer reconstruction of the studied cortical surface.

    PubMed

    Miasnikov, A A; Webster, H H; Dykes, R W

    1999-04-01

    We elaborated two methods used in two previous publications [J. Martinson, H.H. Webster, A.A. Myasnikov, R.W. Dykes, Recognition of temporally structured activity in spontaneously discharging neurons in the somatosensory cortex in waking cats, Brain Res. 750 (1997) 129-140 [16]; H.H. Webster, I. Salimi, A.A. Myasnikov, R.W. Dykes. The effects of peripheral deafferentation on spontaneously bursting neurons in the somatosensory cortex of waking cats, Brain Res. 750 (1997) 109-121 [21

  10. Inter-observer reliability of forceful exertion analysis based on video-recordings.

    PubMed

    Bao, S; Howard, N; Spielholz, P; Silverstein, B

    2010-09-01

    The objectives were to examine inter-observer reliability of job-level forceful exertion analyses and temporal agreement of detailed time study results. Three observers performed the analyses on 12 different jobs. Continuous duration, frequency and % time of lifting, pushing/pulling, power and pinch gripping exertions and estimated level of the exertions were obtained. Intraclass correlation coefficient and variance components were computed. Temporal agreement analyses of raw time study data were performed. The inter-observer reliability was good for most job-level exposure parameters (continuous duration, frequency and % time of forceful exertions), but only fair to moderate for the estimated level of forceful exertions. The finding that the between-observer variability was less than the between-exertion variability confirmed that the forceful exertion analysis method used in the present study can detect job exertion differences.Using three observers to perform detailed time studies on task activities and getting consensus of the majority can increase the between-observer agreement up to 97%. STATEMENT OF RELEVANCE: The results inform researchers that inter-observer reliability for job-level exposure measurement of forceful exertion analysis obtained from detailed time studies is generally good, but the observers' ability in the estimation of forceful exertion level can be poor. It also provides information on the temporal agreement of detailed forceful exertion analysis and guidelines on achieving better agreement for studies where accurate synchronisation of task activities and direct physiological/biomechanical measurements is crucial. PMID:20737338

  11. 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

  12. Chronic Exertional Compartment Syndrome Testing.

    PubMed

    Flick, David; Flick, Renee

    2015-01-01

    Chronic exertional compartment syndrome is diagnosed based on historical and physical exam findings combined with elevated intracompartmental pressures. Direct static testing with a large bore needle device is the most common instrument used for diagnosis. Based on the most recent systematic reviews, there is poor evidence for the traditional diagnostic pressures used in practice with no standardization of the procedure. New research has introduced a standardized approach with dynamic testing of the limb with transducer-tipped catheters. Less invasive methods of testing using radiologic techniques are currently under investigation. A detailed understanding of the anatomy and physiology of the limb is paramount in executing a safe and accurate procedure. PMID:26359839

  13. Does mental exertion alter maximal muscle activation?

    PubMed Central

    Rozand, Vianney; Pageaux, Benjamin; Marcora, Samuele M.; Papaxanthis, Charalambos; Lepers, Romuald

    2014-01-01

    Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 min each: (i) high mental exertion (incongruent Stroop task), (ii) moderate mental exertion (congruent Stroop task), (iii) low mental exertion (watching a movie). In each condition, mental exertion was combined with 10 intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 min). Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors. PMID:25309404

  14. 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

  15. Exertion injuries in female athletes.

    PubMed Central

    Orava, S.; Hulkko, A.; Jormakka, E.

    1981-01-01

    Because sports injuries in men form most of the available statistics, the reportage of injuries in female athletes is sparse. We describe exertion injuries and disorders in 281 women athletes, all of which hampered athletic training or performances. Sixty per cent of the injuries occurred to girls ages between 12-19 years, and about forty-eight per cent were track and field athletes. The most common sites of injury were the ankle, foot, heel and leg. Osteochondritic disorders were the most typical injuries in the series, and the chronic medical tibial syndrome was the injury that needed surgical treatment most frequently. Overuse injuries seem to differ very little from each other in the events included in this survey. Images p229-a p229-b p229-c PMID:6797496

  16. Exertion injuries in female athletes.

    PubMed

    Orava, S; Hulkko, A; Jormakka, E

    1981-12-01

    Because sports injuries in men form most of the available statistics, the reportage of injuries in female athletes is sparse. We describe exertion injuries and disorders in 281 women athletes, all of which hampered athletic training or performances. Sixty per cent of the injuries occurred to girls ages between 12-19 years, and about forty-eight per cent were track and field athletes. The most common sites of injury were the ankle, foot, heel and leg. Osteochondritic disorders were the most typical injuries in the series, and the chronic medical tibial syndrome was the injury that needed surgical treatment most frequently. Overuse injuries seem to differ very little from each other in the events included in this survey. PMID:6797496

  17. Exertional leg pain in the athlete.

    PubMed

    Rajasekaran, Sathish; Kvinlaug, Kylie; Finnoff, Jonathan T

    2012-12-01

    Exertional leg pain is a common condition seen in athletes and the general population. Although the differential diagnosis of exertional leg pain is broad, this article focuses on the incidence, anatomy, pathophysiology, clinical presentation, diagnostic evaluation, management, and return-to-play guidelines of chronic exertional compartment syndrome and vascular and nerve entrapment etiologies. PMID:23245661

  18. 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. PMID:27294694

  19. Temporal resolution of misfolded prion protein transport, accumulation, glial activation, and neuronal death in the retinas of mice inoculated with scrapie: relevance to biomarkers of prion disease progression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Vestibular Neuronitis

    MedlinePlus

    ... Prevent Painful Swimmer's Ear Additional Content Medical News Vestibular Neuronitis By Lawrence R. Lustig, MD NOTE: This ... Drugs Herpes Zoster Oticus Meniere Disease Purulent Labyrinthitis Vestibular Neuronitis Vestibular neuronitis is a disorder characterized by ...

  1. 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

  2. Spiking neurons in a hierarchical self-organizing map model can learn to develop spatial and temporal properties of entorhinal grid cells and hippocampal place cells.

    PubMed

    Pilly, Praveen K; Grossberg, Stephen

    2013-01-01

    Medial entorhinal grid cells and hippocampal place cells provide neural correlates of spatial representation in the brain. A place cell typically fires whenever an animal is present in one or more spatial regions, or places, of an environment. A grid cell typically fires in multiple spatial regions that form a regular hexagonal grid structure extending throughout the environment. Different grid and place cells prefer spatially offset regions, with their firing fields increasing in size along the dorsoventral axes of the medial entorhinal cortex and hippocampus. The spacing between neighboring fields for a grid cell also increases along the dorsoventral axis. This article presents a neural model whose spiking neurons operate in a hierarchy of self-organizing maps, each obeying the same laws. This spiking GridPlaceMap model simulates how grid cells and place cells may develop. It responds to realistic rat navigational trajectories by learning grid cells with hexagonal grid firing fields of multiple spatial scales and place cells with one or more firing fields that match neurophysiological data about these cells and their development in juvenile rats. The place cells represent much larger spaces than the grid cells, which enable them to support navigational behaviors. Both self-organizing maps amplify and learn to categorize the most frequent and energetic co-occurrences of their inputs. The current results build upon a previous rate-based model of grid and place cell learning, and thus illustrate a general method for converting rate-based adaptive neural models, without the loss of any of their analog properties, into models whose cells obey spiking dynamics. New properties of the spiking GridPlaceMap model include the appearance of theta band modulation. The spiking model also opens a path for implementation in brain-emulating nanochips comprised of networks of noisy spiking neurons with multiple-level adaptive weights for controlling autonomous adaptive robots

  3. Spiking Neurons in a Hierarchical Self-Organizing Map Model Can Learn to Develop Spatial and Temporal Properties of Entorhinal Grid Cells and Hippocampal Place Cells

    PubMed Central

    Pilly, Praveen K.; Grossberg, Stephen

    2013-01-01

    Medial entorhinal grid cells and hippocampal place cells provide neural correlates of spatial representation in the brain. A place cell typically fires whenever an animal is present in one or more spatial regions, or places, of an environment. A grid cell typically fires in multiple spatial regions that form a regular hexagonal grid structure extending throughout the environment. Different grid and place cells prefer spatially offset regions, with their firing fields increasing in size along the dorsoventral axes of the medial entorhinal cortex and hippocampus. The spacing between neighboring fields for a grid cell also increases along the dorsoventral axis. This article presents a neural model whose spiking neurons operate in a hierarchy of self-organizing maps, each obeying the same laws. This spiking GridPlaceMap model simulates how grid cells and place cells may develop. It responds to realistic rat navigational trajectories by learning grid cells with hexagonal grid firing fields of multiple spatial scales and place cells with one or more firing fields that match neurophysiological data about these cells and their development in juvenile rats. The place cells represent much larger spaces than the grid cells, which enable them to support navigational behaviors. Both self-organizing maps amplify and learn to categorize the most frequent and energetic co-occurrences of their inputs. The current results build upon a previous rate-based model of grid and place cell learning, and thus illustrate a general method for converting rate-based adaptive neural models, without the loss of any of their analog properties, into models whose cells obey spiking dynamics. New properties of the spiking GridPlaceMap model include the appearance of theta band modulation. The spiking model also opens a path for implementation in brain-emulating nanochips comprised of networks of noisy spiking neurons with multiple-level adaptive weights for controlling autonomous adaptive robots

  4. 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. PMID:26181673

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

    PubMed

    Garagnani, Max; Pulvermüller, Friedemann

    2013-10-01

    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

  6. Gender and contraction mode on perceived exertion.

    PubMed

    Pincivero, D M; Polen, R R; Byrd, B N

    2010-05-01

    The purpose of this study was to examine perceived exertion responses during concentric and eccentric elbow flexor contractions between young adult men and women. Thirty healthy young adults participated in two experimental sessions. During the first session, subjects performed five concentric isokinetic maximal voluntary contractions (MVC) of elbow flexion, followed by nine, randomly-ordered sub-maximal contractions (10-90% MVC). The same procedures were repeated during the second session, with the exception that eccentric contractions were performed. Subjects rated their perceived exertion following the sub-maximal contractions with the Borg category-ratio scale. Perceived exertion was significantly (p<0.05) less than equivalent values on the CR-10 scale at intensities greater than, and equal to, 30% MVC. A three-factor interaction between 30-40% MVC indicated that perceived exertion increased more during the eccentric, than concentric, contractions in women, while the opposite pattern was evident for the men. There were no significant contraction mode or gender differences. Power function modeling revealed that perceived exertion increased in a negatively accelerating manner, except for the men performing eccentric exercise. Perceived exertion increases in a similar non-linear manner between men and women during concentric contractions, while men exhibited a statistically linear pattern during eccentric contractions. PMID:20148376

  7. Prophylactic treatment with melatonin after status epilepticus: effects on epileptogenesis, neuronal damage, and behavioral changes in a kainate model of temporal lobe epilepsy.

    PubMed

    Tchekalarova, Jana; Petkova, Zlatina; Pechlivanova, Daniela; Moyanova, Slavianka; Kortenska, Lidia; Mitreva, Rumiana; Lozanov, Valentin; Atanasova, Dimitrina; Lazarov, Nikolai; Stoynev, Alexander

    2013-04-01

    Melatonin is a potent antioxidant which showed anticonvulsant activities both in experimental and clinical studies. In the present study, we examined the effect of melatonin treatment (10mg/kg/day, diluted in drinking water, 8 weeks) during epileptogenesis on the consequences of a kainate (KA)-induced status epilepticus (SE) in rats. Melatonin increased the latency in the appearance of spontaneous recurrent seizures (SRSs) and decreased their frequency only during the treatment period. The behavioral alterations associated with hyperactivity, depression-like behavior during the light phase, and deficits in hippocampus-dependent working memory were positively affected by melatonin treatment in rats with epilepsy. Melatonin reduced the neuronal damage in the CA1 area of the hippocampus and piriform cortex and recovered the decrease of hippocampal serotonin (5-HT) level in rats with epilepsy. Taken together, long-term melatonin treatment after SE was unable to suppress the development of epileptogenesis. However, it showed a potential in reducing some of the deleterious alterations that develop during the chronic epileptic state in a diurnal phase-dependent mode. PMID:23435277

  8. Depolarizing GABA acts on intrinsically bursting pyramidal neurons to drive giant depolarizing potentials in the immature hippocampus.

    PubMed

    Sipilä, Sampsa T; Huttu, Kristiina; Soltesz, Ivan; Voipio, Juha; Kaila, Kai

    2005-06-01

    Spontaneous periodic network events are a characteristic feature of developing neuronal networks, and they are thought to play a crucial role in the maturation of neuronal circuits. In the immature hippocampus, these types of events are seen in intracellular recordings as giant depolarizing potentials (GDPs) during the stage of neuronal development when GABA(A)-mediated transmission is depolarizing. However, the precise mechanism how GABAergic transmission promotes GDP occurrence is not known. Using whole-cell, cell-attached, perforated-patch, and field-potential recordings in hippocampal slices, we demonstrate here that CA3 pyramidal neurons in the newborn rat generate intrinsic bursts when depolarized. Furthermore, the characteristic rhythmicity of GDP generation is not based on a temporally patterned output of the GABAergic interneuronal network. However, GABAergic depolarization plays a key role in promoting voltage-dependent, intrinsic pyramidal bursting activity. The present data indicate that glutamatergic CA3 neurons have an instructive, pacemaker role in the generation of GDPs, whereas both synaptic and tonic depolarizing GABAergic mechanisms exert a temporally nonpatterned, facilitatory action in the generation of these network events. PMID:15930375

  9. Methylprednisolone exerts neuroprotective effects by regulating autophagy and apoptosis

    PubMed Central

    Gao, Wei; Chen, Shu-rui; Wu, Meng-yao; Gao, Kai; Li, Yuan-long; Wang, Hong-yu; Li, Chen-yuan; Li, Hong

    2016-01-01

    Methylprednisolone markedly reduces autophagy and apoptosis after secondary spinal cord injury. Here, we investigated whether pretreatment of cells with methylprednisolone would protect neuron-like cells from subsequent oxidative damage via suppression of autophagy and apoptosis. Cultured N2a cells were pretreated with 10 µM methylprednisolone for 30 minutes, then exposed to 100 µM H2O2 for 24 hours. Inverted phase contrast microscope images, MTT assay, flow cytometry and western blot results showed that, compared to cells exposed to 100 µM H2O2 alone, cells pretreated with methylprednisolone had a significantly lower percentage of apoptotic cells, maintained a healthy morphology, and showed downregulation of autophagic protein light chain 3B and Beclin-1 protein expression. These findings indicate that methylprednisolone exerted neuroprotective effects against oxidative damage by suppressing autophagy and apoptosis. PMID:27335569

  10. Methylprednisolone exerts neuroprotective effects by regulating autophagy and apoptosis.

    PubMed

    Gao, Wei; Chen, Shu-Rui; Wu, Meng-Yao; Gao, Kai; Li, Yuan-Long; Wang, Hong-Yu; Li, Chen-Yuan; Li, Hong

    2016-05-01

    Methylprednisolone markedly reduces autophagy and apoptosis after secondary spinal cord injury. Here, we investigated whether pretreatment of cells with methylprednisolone would protect neuron-like cells from subsequent oxidative damage via suppression of autophagy and apoptosis. Cultured N2a cells were pretreated with 10 µM methylprednisolone for 30 minutes, then exposed to 100 µM H2O2 for 24 hours. Inverted phase contrast microscope images, MTT assay, flow cytometry and western blot results showed that, compared to cells exposed to 100 µM H2O2 alone, cells pretreated with methylprednisolone had a significantly lower percentage of apoptotic cells, maintained a healthy morphology, and showed downregulation of autophagic protein light chain 3B and Beclin-1 protein expression. These findings indicate that methylprednisolone exerted neuroprotective effects against oxidative damage by suppressing autophagy and apoptosis. PMID:27335569

  11. 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

  12. 3D Visualization of the Temporal and Spatial Spread of Tau Pathology Reveals Extensive Sites of Tau Accumulation Associated with Neuronal Loss and Recognition Memory Deficit in Aged Tau Transgenic Mice

    PubMed Central

    Fu, Hongjun; Hussaini, S. Abid; Wegmann, Susanne; Profaci, Caterina; Daniels, Jacob D.; Herman, Mathieu; Emrani, Sheina; Figueroa, Helen Y.; Hyman, Bradley T.; Davies, Peter; Duff, Karen E.

    2016-01-01

    3D volume imaging using iDISCO+ was applied to observe the spatial and temporal progression of tau pathology in deep structures of the brain of a mouse model that recapitulates the earliest stages of Alzheimer’s disease (AD). Tau pathology was compared at four timepoints, up to 34 months as it spread through the hippocampal formation and out into the neocortex along an anatomically connected route. Tau pathology was associated with significant gliosis. No evidence for uptake and accumulation of tau by glia was observed. Neuronal cells did appear to have internalized tau, including in extrahippocampal areas as a small proportion of cells that had accumulated human tau protein did not express detectible levels of human tau mRNA. At the oldest timepoint, mature tau pathology in the entorhinal cortex (EC) was associated with significant cell loss. As in human AD, mature tau pathology in the EC and the presence of tau pathology in the neocortex correlated with cognitive impairment. 3D volume imaging is an ideal technique to easily monitor the spread of pathology over time in models of disease progression. PMID:27466814

  13. 3D Visualization of the Temporal and Spatial Spread of Tau Pathology Reveals Extensive Sites of Tau Accumulation Associated with Neuronal Loss and Recognition Memory Deficit in Aged Tau Transgenic Mice.

    PubMed

    Fu, Hongjun; Hussaini, S Abid; Wegmann, Susanne; Profaci, Caterina; Daniels, Jacob D; Herman, Mathieu; Emrani, Sheina; Figueroa, Helen Y; Hyman, Bradley T; Davies, Peter; Duff, Karen E

    2016-01-01

    3D volume imaging using iDISCO+ was applied to observe the spatial and temporal progression of tau pathology in deep structures of the brain of a mouse model that recapitulates the earliest stages of Alzheimer's disease (AD). Tau pathology was compared at four timepoints, up to 34 months as it spread through the hippocampal formation and out into the neocortex along an anatomically connected route. Tau pathology was associated with significant gliosis. No evidence for uptake and accumulation of tau by glia was observed. Neuronal cells did appear to have internalized tau, including in extrahippocampal areas as a small proportion of cells that had accumulated human tau protein did not express detectible levels of human tau mRNA. At the oldest timepoint, mature tau pathology in the entorhinal cortex (EC) was associated with significant cell loss. As in human AD, mature tau pathology in the EC and the presence of tau pathology in the neocortex correlated with cognitive impairment. 3D volume imaging is an ideal technique to easily monitor the spread of pathology over time in models of disease progression. PMID:27466814

  14. 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

  15. [Direct neuronal effects of statins].

    PubMed

    Bösel, J; Endres, M

    2006-03-01

    Statins, i.e. HMG-CoA reductase inhibitors, reduce the risk of stroke and may have therapeutic potential for other neurologic diseases, including multiple sclerosis and Alzheimer's disease. In addition to lowering cholesterol levels, statins exert a number of cholesterol-independent (pleiotropic) effects. While endothelial, anti-thrombotic, anti-inflammatory, and immunomodulatory, i.e. peripheral, effects of statins are well known, little is known about the direct effects on neurons. This may be of clinical relevance because some statins are able to cross the blood-brain barrier. Recent experimental studies demonstrate that statins reduce the activity of neuronal glutamate receptors and protect neurons from excitotoxic insults. At higher doses, however, statins may also inhibit neurite sprouting and even induce neuronal apoptosis. PMID:16028081

  16. 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.

  17. The force exerted by a fireball

    NASA Astrophysics Data System (ADS)

    Makrinich, G.; Fruchtman, A.

    2014-02-01

    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.

  18. Neuronal polarization.

    PubMed

    Takano, Tetsuya; Xu, Chundi; Funahashi, Yasuhiro; Namba, Takashi; Kaibuchi, Kozo

    2015-06-15

    Neurons are highly polarized cells with structurally and functionally distinct processes called axons and dendrites. This polarization underlies the directional flow of information in the central nervous system, so the establishment and maintenance of neuronal polarization is crucial for correct development and function. Great progress in our understanding of how neurons establish their polarity has been made through the use of cultured hippocampal neurons, while recent technological advances have enabled in vivo analysis of axon specification and elongation. This short review and accompanying poster highlight recent advances in this fascinating field, with an emphasis on the signaling mechanisms underlying axon and dendrite specification in vitro and in vivo. PMID:26081570

  19. Maturation of GABAergic Inhibition Promotes Strengthening of Temporally Coherent Inputs among Convergent Pathways

    PubMed Central

    Kuhlman, Sandra J.; Lu, Jiangteng; Lazarus, Matthew S.; Huang, Z. Josh

    2010-01-01

    Spike-timing-dependent plasticity (STDP), a form of Hebbian plasticity, is inherently stabilizing. Whether and how GABAergic inhibition influences STDP is not well understood. Using a model neuron driven by converging inputs modifiable by STDP, we determined that a sufficient level of inhibition was critical to ensure that temporal coherence (correlation among presynaptic spike times) of synaptic inputs, rather than initial strength or number of inputs within a pathway, controlled postsynaptic spike timing. Inhibition exerted this effect by preferentially reducing synaptic efficacy, the ability of inputs to evoke postsynaptic action potentials, of the less coherent inputs. In visual cortical slices, inhibition potently reduced synaptic efficacy at ages during but not before the critical period of ocular dominance (OD) plasticity. Whole-cell recordings revealed that the amplitude of unitary IPSCs from parvalbumin positive (Pv+) interneurons to pyramidal neurons increased during the critical period, while the synaptic decay time-constant decreased. In addition, intrinsic properties of Pv+ interneurons matured, resulting in an increase in instantaneous firing rate. Our results suggest that maturation of inhibition in visual cortex ensures that the temporally coherent inputs (e.g. those from the open eye during monocular deprivation) control postsynaptic spike times of binocular neurons, a prerequisite for Hebbian mechanisms to induce OD plasticity. PMID:20532211

  20. The neuronal and actin commitment: Why do neurons need rings?

    PubMed

    Leite, Sérgio Carvalho; Sousa, Mónica Mendes

    2016-09-01

    The role of the actin cytoskeleton in neurons has been extensively studied in actin-enriched compartments such as the growth cone and dendritic spines. The recent discovery of actin rings in the axon shaft and in dendrites, together with the identification of axon actin trails, has advanced our understanding on actin organization and dynamics in neurons. However, specifically in the case of actin rings, the mechanisms regulating their nucleation and assembly, and the functions that they may exert in axons and dendrites remain largely unexplored. Here we discuss the possible structural, mechanistic and functional properties of the subcortical neuronal cytoskeleton putting the current knowledge in perspective with the information available on actin rings formed in other biological contexts, and with the organization of actin-spectrin lattices in other cell types. The detailed analysis of these novel neuronal actin ring structures, together with the elucidation of the function of actin-binding proteins in neuron biology, has a large potential to uncover new mechanisms of neuronal function under normal conditions that may have impact in our understanding of axon degeneration and regeneration. © 2016 Wiley Periodicals, Inc. PMID:26784007

  1. Exercise exerts neuroprotective effects on Parkinson's disease model of rats.

    PubMed

    Tajiri, Naoki; Yasuhara, Takao; Shingo, Tetsuro; Kondo, Akihiko; Yuan, Wenji; Kadota, Tomohito; Wang, Feifei; Baba, Tanefumi; Tayra, Judith Thomas; Morimoto, Takamasa; Jing, Meng; Kikuchi, Yoichiro; Kuramoto, Satoshi; Agari, Takashi; Miyoshi, Yasuyuki; Fujino, Hidemi; Obata, Futoshi; Takeda, Isao; Furuta, Tomohisa; Date, Isao

    2010-01-15

    Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinson's disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinson's disease model of rats with subsequent improvement in deteriorated motor function. PMID:19900418

  2. 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

  3. 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.

  4. Audiotactile interactions in temporal perception.

    PubMed

    Occelli, Valeria; Spence, Charles; Zampini, Massimiliano

    2011-06-01

    In the present review, we focus on how commonalities in the ontogenetic development of the auditory and tactile sensory systems may inform the interplay between these signals in the temporal domain. In particular, we describe the results of behavioral studies that have investigated temporal resolution (in temporal order, synchrony/asynchrony, and simultaneity judgment tasks), as well as temporal numerosity perception, and similarities in the perception of frequency across touch and hearing. The evidence reviewed here highlights features of audiotactile temporal perception that are distinctive from those seen for other pairings of sensory modalities. For instance, audiotactile interactions are characterized in certain tasks (e.g., temporal numerosity judgments) by a more balanced reciprocal influence than are other modality pairings. Moreover, relative spatial position plays a different role in the temporal order and temporal recalibration processes for audiotactile stimulus pairings than for other modality pairings. The effect exerted by both the spatial arrangement of stimuli and attention on temporal order judgments is described. Moreover, a number of audiotactile interactions occurring during sensory-motor synchronization are highlighted. We also look at the audiotactile perception of rhythm and how it may be affected by musical training. The differences emerging from this body of research highlight the need for more extensive investigation into audiotactile temporal interactions. We conclude with a brief overview of some of the key issues deserving of further research in this area. PMID:21400125

  5. Return to physical activity after exertional rhabdomyolysis.

    PubMed

    O'Connor, Francis G; Brennan, Fred H; Campbell, William; Heled, Yuval; Deuster, Patricia

    2008-01-01

    Exertional rhabdomyolysis (ER) is a condition characterized by muscle pain, swelling, and weakness following some exertional stress, with or without concomitant heat stress. Athletes who experience ER often present to the emergency department, the training room, or the physician's office seeking guidance and care for this condition, often feeling it is simply normal delayed onset muscle soreness. The astute clinician must perform a thorough history and focused exam, in addition to ordering a serum creatine kinase (CK) and urinalysis. In this clinical setting, a CK equal to or greater than five times normal or a urine dipstick testing positive for blood with no demonstrable red blood cells upon microscopic assessment confirms the diagnosis. A urine or serum myoglobin is more definitive when expeditiously available. After treatment for ER, the provider must risk-stratify the athlete for risk of recurrence, consider further testing, and make the difficult decision on when, if, and under what conditions the athlete can safely return to play. PMID:19005354

  6. Neuronal arithmetic

    PubMed Central

    Silver, R. Angus

    2016-01-01

    The vast computational power of the brain has traditionally been viewed as arising from the complex connectivity of neural networks, in which an individual neuron acts as a simple linear summation and thresholding device. However, recent studies show that individual neurons utilize a wealth of nonlinear mechanisms to transform synaptic input into output firing. These mechanisms can arise from synaptic plasticity, synaptic noise, and somatic and dendritic conductances. This tool kit of nonlinear mechanisms confers considerable computational power on both morphologically simple and more complex neurons, enabling them to perform a range of arithmetic operations on signals encoded in a variety of different ways. PMID:20531421

  7. Spatially selective photoconductive stimulation of live neurons

    PubMed Central

    Campbell, Jacob; Singh, Dipika; Hollett, Geoffrey; Dravid, Shashank M.; Sailor, Michael J.; Arikkath, Jyothi

    2014-01-01

    Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques. While technically powerful, chemical stimulation has limited spatial resolution and microelectrode and optogenetic techniques require specialized equipment and expertise. We report an optimized and improved technique for laser based photoconductive stimulation of live neurons using an inverted confocal microscope that overcomes these limitations. The advantages of this approach include its non-invasive nature and adaptability to temporal and spatial manipulation. We demonstrate that the technique can be manipulated to achieve spatially selective stimulation of live neurons. Coupled with live imaging of fluorescent indicators, this simple and efficient technique should allow for significant advances in neuronal cell biology. PMID:24904287

  8. [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. PMID:27406773

  9. 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

  10. Genetic polymorphisms associated with exertional rhabdomyolysis.

    PubMed

    Deuster, Patricia A; Contreras-Sesvold, Carmen L; O'Connor, Francis G; Campbell, William W; Kenney, Kimbra; Capacchione, John F; Landau, Mark E; Muldoon, Sheila M; Rushing, Elisabeth J; Heled, Yuval

    2013-08-01

    Exertional rhabdomyolysis (ER) occurs in young, otherwise healthy, individuals principally during strenuous exercise, athletic, and military training. Although many risk factors have been offered, it is unclear why some individuals develop ER when participating in comparable levels of physical exertion under identical environmental conditions and others do not. This study investigated possible genetic polymorphisms that might help explain ER. DNA samples derived from a laboratory-based study of persons who had never experienced an episode of ER (controls) and clinical ER cases referred for testing over the past several years were analyzed for single nucleotide polymorphisms (SNPs) in candidate genes. These included angiotensin I converting enzyme (ACE), α-actinin-3 (ACTN3), creatine kinase muscle isoform (CKMM), heat shock protein A1B (HSPA1B), interleukin 6 (IL6), myosin light chain kinase (MYLK), adenosine monophosphate deaminase 1 (AMPD1), and sickle cell trait (HbS). Population included 134 controls and 47 ER cases. The majority of ER cases were men (n = 42/47, 89.4 %); the five women with ER were Caucasian. Eighteen African Americans (56.3 %) were ER cases. Three SNPs were associated with ER: CKMM Ncol, ACTN3 R577X, and MYLK C37885A. ER cases were 3.1 times more likely to have the GG genotype of CKMM (odds ratio/OR = 3.1, confidence interval/CI 1.33-7.10), 3.0 times for the XX genotype of ACTN3 SNP (OR = 2.97, CI 1.30-3.37), and 5.7 times for an A allele of MYLK (OR = 21.35, CI 2.60-12.30). All persons with HbS were also ER cases. Three distinct polymorphisms were associated with ER. Further work will be required to replicate these findings and determine the mechanism(s) whereby these variants might confer susceptibility. PMID:23543093

  11. 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,…

  12. The timing of neuronal loss across adolescence in the medial prefrontal cortex of male and female rats.

    PubMed

    Willing, J; Juraska, J M

    2015-08-20

    Adolescence is a critical period of brain maturation characterized by the reorganization of interacting neural networks. In particular the prefrontal cortex (PFC), a region involved in executive function, undergoes synaptic and neuronal pruning during this time in both humans and rats. Our laboratory has previously shown that rats lose neurons in the medial prefrontal cortex (mPFC) and there is an increase in white matter under the frontal cortex between adolescence and adulthood. Female rats lose more neurons during this period, and ovarian hormones may play a role as ovariectomy before adolescence prevents neuronal loss. However, little is known regarding the timing of neuroanatomical changes that occur between early adolescence and adulthood. In the present study, we quantified the number of neurons and glia in the male and female mPFC at multiple time points from preadolescence through adulthood (postnatal days 25, 35, 45, 60 and 90). Females, but not males, lost a significant number of neurons in the mPFC between days 35 and 45, coinciding with the onset of puberty. Counts of GABA immunoreactive cell bodies indicated that the neurons lost were not primarily GABAergic. These results suggest that in females, pubertal hormones may exert temporally specific changes in PFC anatomy. As expected, both males and females gained white matter under the PFC throughout adolescence, though these gains in females were diminished after day 35, but not in males. The differences in cell loss in males and females may lead to differential vulnerability to external influences and dysfunctions of the PFC that manifest in adolescence. PMID:26047728

  13. Mechanisms for generating temporal filters in the electrosensory system.

    PubMed

    Rose, G J; Fortune, E S

    1999-05-01

    Temporal patterns of sensory information are important cues in behaviors ranging from spatial analyses to communication. Neural representations of the temporal structure of sensory signals include fluctuations in the discharge rate of neurons over time (peripheral nervous system) and the differential level of activity in neurons tuned to particular temporal features (temporal filters in the central nervous system). This paper presents our current understanding of the mechanisms responsible for the transformations between these representations in electric fish of the genus Eigenmannia. The roles of passive and active membrane properties of neurons, and frequency-dependent gain-control mechanisms are discussed. PMID:10210668

  14. Cough, exertional, and other miscellaneous headaches.

    PubMed

    Sands, G H; Newman, L; Lipton, R

    1991-05-01

    We have discussed several miscellaneous headache disorders not associated with structural brain disease. The first group included those headaches provoked by "exertional" triggers in various forms. These include benign cough headache, BEH, and headache associated with sexual activity. The IHS diagnostic criteria were discussed. Benign exertional headache and cough headache were discussed together because of their substantial similarities. In general, BEH is characterized by severe, short-lived pain after coughing, sneezing, lifting a burden, sexual activity, or other similar brief effort. Structural disease of the brain or skull was the most important differential diagnosis for these disorders, with posterior fossa mass lesions being identified as the most common organic etiology. Magnetic resonance imaging with special attention to the posterior fossa and foramen magnum is the preferred method for evaluating these patients. Indomethacin is the treatment of choice. The headache associated with sexual activity is dull in the early phases of sexual excitement and becomes intense at orgasm. This headache is unpredictable in occurrence. Like BEH, the headache associated with sexual activity can be a manifestation of structural disease. Subarachnoid hemorrhage must be excluded, by CT scanning and CSF examination, in patients with the sexual headache. Benign headache associated with sexual activity has been successfully treated with indomethacin and beta-blockers. The second miscellaneous group of headache disorders includes those provoked by eating something cold or food additives, and by environmental stimuli. Idiopathic stabbing headache does not have a known trigger and appears frequently in migraineurs. Its occurrence may also herald the termination of an attack of cluster headache. Indomethacin treatment provides significant relief. Three headaches triggered by substances that are eaten were reviewed: ingestion of a cold stimulus, nitrate/nitrite-induced headache

  15. 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.

  16. 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. PMID:27183057

  17. 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.

  18. Stochastic models of neuronal dynamics

    PubMed Central

    Harrison, L.M; David, O; Friston, K.J

    2005-01-01

    Cortical activity is the product of interactions among neuronal populations. Macroscopic electrophysiological phenomena are generated by these interactions. In principle, the mechanisms of these interactions afford constraints on biologically plausible models of electrophysiological responses. In other words, the macroscopic features of cortical activity can be modelled in terms of the microscopic behaviour of neurons. An evoked response potential (ERP) is the mean electrical potential measured from an electrode on the scalp, in response to some event. The purpose of this paper is to outline a population density approach to modelling ERPs. We propose a biologically plausible model of neuronal activity that enables the estimation of physiologically meaningful parameters from electrophysiological data. The model encompasses four basic characteristics of neuronal activity and organization: (i) neurons are dynamic units, (ii) driven by stochastic forces, (iii) organized into populations with similar biophysical properties and response characteristics and (iv) multiple populations interact to form functional networks. This leads to a formulation of population dynamics in terms of the Fokker–Planck equation. The solution of this equation is the temporal evolution of a probability density over state-space, representing the distribution of an ensemble of trajectories. Each trajectory corresponds to the changing state of a neuron. Measurements can be modelled by taking expectations over this density, e.g. mean membrane potential, firing rate or energy consumption per neuron. The key motivation behind our approach is that ERPs represent an average response over many neurons. This means it is sufficient to model the probability density over neurons, because this implicitly models their average state. Although the dynamics of each neuron can be highly stochastic, the dynamics of the density is not. This means we can use Bayesian inference and estimation tools that have

  19. Motor Neuron Diseases

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Motor Neuron Diseases Information Page Condensed from Motor Neuron Diseases ... and Information Publicaciones en Español What are Motor Neuron Diseases? The motor neuron diseases (MNDs) are a ...

  20. Motor Neuron Diseases

    MedlinePlus

    ... called upper motor neurons ) are transmitted to nerve cells in the brain stem and spinal cord (called lower motor neurons ) and from them to particular muscles. Upper motor neurons direct the lower motor neurons ...

  1. Effects of Temporal Context and Temporal Expectancy on Neural Activity in Inferior Temporal Cortex

    PubMed Central

    Anderson, Britt; Sheinberg, David L.

    2008-01-01

    Timing is critical. The same event can mean different things at different times and some events are more likely to occur at one time than another. We used a cued visual classification task to evaluate how changes in temporal context affect neural responses in inferior temporal cortex, an extrastriate visual area known to be involved in object processing. On each trial a first image cued a temporal delay before a second target image appeared. The animal’s task was to classify the second image by pressing one of two buttons previously associated with that target. All images were used as both cues and targets. Whether an image cued a delay time or signaled a button press depended entirely upon whether it was the first or second picture in a trial. This paradigm allowed us to compare inferior temporal cortex neural activity to the same image subdivided by temporal context and expectation. Neuronal spiking was more robust and visually evoked local field potentials (LFP’s) larger for target presentations than for cue presentations. On invalidly cued trials, when targets appeared unexpectedly early, the magnitude of the evoked LFP was reduced and delayed and neuronal spiking was attenuated. Spike field coherence increased in the beta-gamma frequency range for expected targets. In conclusion, different neural responses in higher order ventral visual cortex may occur for the same visual image based on manipulations of temporal attention. PMID:18206961

  2. 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

  3. The neuronal code for number.

    PubMed

    Nieder, Andreas

    2016-06-01

    Humans and non-human primates share an elemental quantification system that resides in a dedicated neural network in the parietal and frontal lobes. In this cortical network, 'number neurons' encode the number of elements in a set, its cardinality or numerosity, irrespective of stimulus appearance across sensory motor systems, and from both spatial and temporal presentation arrays. After numbers have been extracted from sensory input, they need to be processed to support goal-directed behaviour. Studying number neurons provides insights into how information is maintained in working memory and transformed in tasks that require rule-based decisions. Beyond an understanding of how cardinal numbers are encoded, number processing provides a window into the neuronal mechanisms of high-level brain functions. PMID:27150407

  4. Dietary polyphenols exert neuroprotective effects by attenuating neuronal and astrocytic damage in cerebral ischemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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.

  6. 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…

  7. 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,...

  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, 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,...

  10. 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…

  11. 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... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms...

  12. 20 CFR 416.969a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Exertional and nonexertional limitations. 416.969a 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...

  13. 20 CFR 416.969a - 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. 416.969a 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...

  14. 20 CFR 416.969a - 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. 416.969a 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...

  15. 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... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms...

  16. 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... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms...

  17. 20 CFR 416.969a - 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. 416.969a 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...

  18. 20 CFR 404.1569a - Exertional and nonexertional limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Exertional and nonexertional limitations. 404.1569a 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...

  19. 20 CFR 416.969a - 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. 416.969a 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...

  20. 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... of jobs by various exertional levels (sedentary, light, medium, heavy, and very heavy) in terms...

  1. 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,...

  2. Unrecognized acute exertional compartment syndrome of the leg and treatment.

    PubMed

    Popovic, Nebojsa; Bottoni, Craig; Cassidy, Charles

    2011-04-01

    Acute-on-chronic exertional compartment syndrome is rare and may be easily missed without a high degree of awareness and clinical suspicion. We report a case of unrecognized acute-on-chronic exertional compartment syndrome in a recreational soccer player. The late sequela of this condition, foot drop, was successfully treated with transfer of the peroneus longus tendon. PMID:21667742

  3. 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…

  4. 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.

  5. 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.

  6. 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

  7. Direct conversion of human fibroblasts to induced serotonergic neurons.

    PubMed

    Xu, Z; Jiang, H; Zhong, P; Yan, Z; Chen, S; Feng, J

    2016-01-01

    Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly converted to induced serotonergic (i5HT) neurons by the expression of Ascl1, Foxa2, Lmx1b and FEV. The transdifferentiation was enhanced by p53 knockdown and appropriate culture conditions including hypoxia. The i5HT neurons expressed markers for mature serotonergic neurons, had Ca(2+)-dependent 5HT release and selective 5HT uptake, exhibited spontaneous action potentials and spontaneous excitatory postsynaptic currents. Application of serotonin significantly increased the firing rate of spontaneous action potentials, demonstrating the functional utility of i5HT neurons for studying serotonergic neurotransmission. The availability of human i5HT neurons will be very useful for research and drug discovery on many serotonin-related mental disorders. PMID:26216300

  8. 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

  9. Dopamine modulates excitability of basolateral amygdala neurons in vitro.

    PubMed

    Kröner, Sven; Rosenkranz, J Amiel; Grace, Anthony A; Barrionuevo, German

    2005-03-01

    The amygdala plays a role in affective behaviors, which are modulated by the dopamine (DA) innervation of the basolateral amygdala complex (BLA). Although in vivo studies indicate that activation of DA receptors alters BLA neuronal activity, it is unclear whether DA exerts direct effects on BLA neurons or whether it acts via indirect effects on BLA afferents. Using whole cell patch-clamp recordings in rat brain slices, we investigated the site and mechanisms through which DA regulates the excitability of BLA neurons. Dopamine enhanced the excitability of BLA projection neurons in response to somatic current injections via a postsynaptic effect. Dopamine D1 receptor activation increased excitability and evoked firing, whereas D2 receptor activation increased input resistance. Current- and voltage-clamp experiments in projection neurons showed that D1 receptor activation enhanced excitability by modulating a 4-aminopyridine- and alpha-dendrotoxin-sensitive, slowly inactivating K+ current. Furthermore, DA and D1 receptor activation increased evoked firing in fast-spiking BLA interneurons. Consistent with a postsynaptic modulation of interneuron excitability, DA also increased the frequency of spontaneous inhibitory postsynaptic currents recorded in projection neurons without changing release of GABA. These data demonstrate that DA exerts direct effects on BLA projection neurons and indirect actions via modulation of interneurons that may work in concert to enhance the neuronal response to large, suprathreshold inputs, while suppressing weaker inputs. PMID:15537813

  10. 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

  11. 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

  12. 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

  13. 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

  14. Simple neuron models of ITD sensitive neurons

    NASA Astrophysics Data System (ADS)

    Dasika, Vasant; White, John A.; Colburn, H. Steven

    2002-05-01

    Neurons which show sensitivity to interaural time delay (ITD) exist in both mammalian medial superior olive (MSO), and bird nucleus laminaris (NL). In this study, we examine simple mathematical models of single MSO and NL cells which respond probabilistically to a pair of isolated inputs with a response probability that depends on the input interpulse interval. Inputs are either isolated pulse pairs or pairs of periodic trains, with or without random jitter added to their event times. Refractoriness is incorporated in the input description and/or in the cell model in specified simulations. We find that periodic rate-ITD shapes are shaped by three interacting factors: the cell's temporal response (described by the paired-pulse response), input frequency, and the degree of input synchrony. Paired-pulse responses are able to predict the widths of rate-ITD curves obtained from deterministic periodic input simulations. Reduced input synchrony predictably smears rate-ITD curves. Larger numbers of weaker inputs yield stronger rate-ITD modulation than a few strong inputs. Model response is compared with in vivo and in vitro MSO and NL physiological data. Comparisons with published analytical models as well as more complex and realistic physiological cell models are examined.

  15. 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

  16. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    NASA Astrophysics Data System (ADS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B.

    2010-06-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities (<150 or >1000 cells mm-2) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component.

  17. Neuronal Mechanisms and Transformations Encoding Time-Varying Signals.

    PubMed

    Petkov, Christopher I; Bendor, Daniel

    2016-08-17

    Sensation in natural environments requires the analysis of time-varying signals. While previous work has uncovered how a signal's temporal rate is represented by neurons in sensory cortex, in this issue of Neuron, new evidence from Gao et al. (2016) provides insights on the underlying mechanisms. PMID:27537481

  18. Temporal integration at consecutive processing stages in the auditory pathway of the grasshopper.

    PubMed

    Wirtssohn, Sarah; Ronacher, Bernhard

    2015-04-01

    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

  19. 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

  20. Temporal profiling of changes in phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate and diacylglycerol allows comprehensive analysis of phospholipase C-initiated signalling in single neurons1

    PubMed Central

    Nelson, Carl P; Nahorski, Stefan R; Challiss, R A John

    2008-01-01

    Phosphatidylinositol 4,5-bisphosphate (PIP2) fulfils vital signalling roles in an array of cellular processes, yet until recently it has not been possible selectively to visualize real-time changes in PIP2 levels within living cells. Green fluorescent protein (GFP)-labelled Tubby protein (GFP-Tubby) enriches to the plasma membrane at rest and translocates to the cytosol following activation of endogenous Gαq/11-coupled muscarinic acetylcholine receptors in both SH-SY5Y human neuroblastoma cells and primary rat hippocampal neurons. GFP-Tubby translocation is independent of changes in cytosolic inositol 1,4,5-trisphosphate and instead reports dynamic changes in levels of plasma membrane PIP2. In contrast, enhanced GFP (eGFP)-tagged pleckstrin homology domain of phospholipase C (PLCδ1) (eGFP-PH) translocation reports increases in cytosolic inositol 1,4,5-trisphosphate. Comparison of GFP-Tubby, eGFP-PH and the eGFP-tagged C12 domain of protein kinase C-γ [eGFP-C1(2); to detect diacylglycerol] allowed a selective and comprehensive analysis of PLC-initiated signalling in living cells. Manipulating intracellular Ca2+ concentrations in the nanomolar range established that GFP-Tubby responses to a muscarinic agonist were sensitive to intracellular Ca2+ up to 100–200 nM in SH-SY5Y cells, demonstrating the exquisite sensitivity of agonist-mediated PLC activity within the range of physiological resting Ca2+ concentrations. We have also exploited GFP-Tubby selectively to visualize, for the first time, real-time changes in PIP2 in hippocampal neurons. PMID:18665913

  1. Temporal naturalism

    NASA Astrophysics Data System (ADS)

    Smolin, Lee

    2015-11-01

    Two people may claim both to be naturalists, but have divergent conceptions of basic elements of the natural world which lead them to mean different things when they talk about laws of nature, or states, or the role of mathematics in physics. These disagreements do not much affect the ordinary practice of science which is about small subsystems of the universe, described or explained against a background, idealized to be fixed. But these issues become crucial when we consider including the whole universe within our system, for then there is no fixed background to reference observables to. I argue here that the key issue responsible for divergent versions of naturalism and divergent approaches to cosmology is the conception of time. One version, which I call temporal naturalism, holds that time, in the sense of the succession of present moments, is real, and that laws of nature evolve in that time. This is contrasted with timeless naturalism, which holds that laws are immutable and the present moment and its passage are illusions. I argue that temporal naturalism is empirically more adequate than the alternatives, because it offers testable explanations for puzzles its rivals cannot address, and is likely a better basis for solving major puzzles that presently face cosmology and physics. This essay also addresses the problem of qualia and experience within naturalism and argues that only temporal naturalism can make a place for qualia as intrinsic qualities of matter.

  2. Coping with variability in small neuronal networks.

    PubMed

    Calabrese, Ronald L; Norris, Brian J; Wenning, Angela; Wright, Terrence M

    2011-12-01

    Experimental and corresponding modeling studies indicate that there is a 2- to 5-fold variation of intrinsic and synaptic parameters across animals while functional output is maintained. Here, we review experiments, using the heartbeat central pattern generator (CPG) in medicinal leeches, which explore the consequences of animal-to-animal variation in synaptic strength for coordinated motor output. We focus on a set of segmental heart motor neurons that all receive inhibitory synaptic input from the same four premotor interneurons. These four premotor inputs fire in a phase progression and the motor neurons also fire in a phase progression because of differences in synaptic strength profiles of the four inputs among segments. Our work tested the hypothesis that functional output is maintained in the face of animal-to-animal variation in the absolute strength of connections because relative strengths of the four inputs onto particular motor neurons is maintained across animals. Our experiments showed that relative strength is not strictly maintained across animals even as functional output is maintained, and animal-to-animal variations in strength of particular inputs do not correlate strongly with output phase. Further experiments measured the precise temporal pattern of the premotor inputs, the segmental synaptic strength profiles of their connections onto motor neurons, and the temporal pattern (phase progression) of those motor neurons all in the same animal for a series of 12 animals. The analysis of input and output in this sample of 12 individuals suggests that the number (four) of inputs to each motor neuron and the variability of the temporal pattern of input from the CPG across individuals weaken the influence of the strength of individual inputs. Moreover, the temporal pattern of the output varies as much across individuals as that of the input. Essentially, each animal arrives at a unique solution for how the network produces functional output. PMID

  3. The neuronal code(s) of the cerebellum.

    PubMed

    Heck, Detlef H; De Zeeuw, Chris I; Jaeger, Dieter; Khodakhah, Kamran; Person, Abigail L

    2013-11-01

    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. PMID:24198351

  4. 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

  5. Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state.

    PubMed

    Bellay, Timothy; Klaus, Andreas; Seshadri, Saurav; Plenz, Dietmar

    2015-01-01

    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. PMID:26151674

  6. Physiology and pharmacology of striatal neurons.

    PubMed

    Kreitzer, Anatol C

    2009-01-01

    The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function. PMID:19400717

  7. Synchronized action of synaptically coupled chaotic model neurons.

    PubMed

    Abarbanel, H D; Huerta, R; Rabinovich, M I; Rulkov, N F; Rowat, P F; Selverston, A I

    1996-11-15

    Experimental observations of the intracellular recorded electrical activity in individual neurons show that the temporal behavior is often chaotic. We discuss both our own observations on a cell from the stomatogastric central pattern generator of lobster and earlier observations in other cells. In this paper we work with models with chaotic neurons, building on models by Hindmarsh and Rose for bursting, spiking activity in neurons. The key feature of these simplified models of neurons is the presence of coupled slow and fast subsystems. We analyze the model neurons using the same tools employed in the analysis of our experimental data. We couple two model neurons both electrotonically and electrochemically in inhibitory and excitatory fashions. In each of these cases, we demonstrate that the model neurons can synchronize in phase and out of phase depending on the strength of the coupling. For normal synaptic coupling, we have a time delay between the action of one neuron and the response of the other. We also analyze how the synchronization depends on this delay. A rich spectrum of synchronized behaviors is possible for electrically coupled neurons and for inhibitory coupling between neurons. In synchronous neurons one typically sees chaotic motion of the coupled neurons. Excitatory coupling produces essentially periodic voltage trajectories, which are also synchronized. We display and discuss these synchronized behaviors using two "distance" measures of the synchronization. PMID:8888609

  8. Persulfate activation during exertion of total oxidant demand.

    PubMed

    Teel, Amy L; Elloy, Farah C; Watts, Richard J

    2016-09-01

    Total oxidant demand (TOD) is a parameter that is often measured during in situ chemical oxidation (ISCO) treatability studies. The importance of TOD is based on the concept that the oxidant demand created by soil organic matter and other reduced species must be overcome before contaminant oxidation can proceed. TOD testing was originally designed for permanganate ISCO, but has also recently been applied to activated persulfate ISCO. Recent studies have documented that phenoxides activate persulfate; because soil organic matter is rich in phenolic moieties, it may activate persulfate rather than simply exerting TOD. Therefore, the generation of reactive oxygen species was investigated in three soil horizons of varied soil organic carbon content over 5-day TOD testing. Hydroxyl radical may have been generated during TOD exertion, but was likely scavenged by soil organic matter. A high flux of reductants + nucleophiles (e.g. alkyl radicals + superoxide) was generated as TOD was exerted, resulting in the rapid destruction of the probe compound hexachloroethane and the common groundwater contaminant trichloroethylene (TCE). The results of this research document that, unlike permanganate TOD, contaminant destruction does occur as TOD is exerted in persulfate ISCO systems and is promoted by the activation of persulfate by soil organic matter. Future treatability studies for persulfate ISCO should consider contaminant destruction as TOD is exerted, and the potential for persulfate activation by soil organic matter. PMID:27269993

  9. Opioids, Exertion, and Dyspnea: A Review of the Evidence.

    PubMed

    Johnson, Miriam J; Hui, David; Currow, David C

    2016-03-01

    The aim of this paper is to review the evidence for a role for opioids as an intervention for exertion induced breathlessness with regard to exercise tolerance and breathlessness intensity. Current knowledge about exogenous opioids in exertion-induced breathlessness due to disease comes from a variety of phase 2 feasibility or pilot designs with differing duration, doses, drugs, exercise regimes, underlying aetiologies, and outcome measures. They provide interesting data but firm conclusions for either breathlessness severity or exercise endurance cannot be drawn. There are no adequately powered phase 3 trials of opioids which show improved exercise tolerance and/or exertion induced breathlessness. Low dose oral morphine seems well tolerated by most, and is beneficial for breathlessness intensity. Current work to investigate the effect on exercise tolerance is ongoing. PMID:25294225

  10. Perceived exertion and the field-independence--dependence dimension.

    PubMed

    Robertson, R J; Gillespie, R L; McCarthy, J; Rose, K D

    1978-04-01

    Perceived exertion responses were compared between field-independent and field-dependent perceivers at three cycle-ergometer pedalling rates. 50 male subjects were classified according to mode of field approach on the basis of their performance on an embedded-figures test. Power output was held constant at 840 kpm/min., while pedalling rate was randomly set at 40, 60, or 80 rpm. Significant differences between the field-independent and -dependent groups were not found at the three pedalling rates for any of the physiological variables or for over-all, legs and chest ratings of perceived exertion. The extent of differentiated psychological functioning did not account for individual differences in perceptual reactance during muscular exertion. PMID:662550

  11. 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

  12. 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. PMID:27330050

  13. 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.

  14. Adaptation to speed in macaque middle temporal and medial superior temporal areas.

    PubMed

    Price, Nicholas S C; Born, Richard T

    2013-03-01

    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. PMID:23467352

  15. 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

  16. Identifying local and descending inputs for primary sensory neurons.

    PubMed

    Zhang, Yi; Zhao, Shengli; Rodriguez, Erica; Takatoh, Jun; Han, Bao-Xia; Zhou, Xiang; Wang, Fan

    2015-10-01

    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

  17. 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

  18. Brain-Derived Estrogen Exerts Anti-inflammatory and Neuroprotective Actions in the Rat Hippocampus

    PubMed Central

    Zhang, Quan-Guang; Wang, Ruimin; Tang, Hui; Dong, Yan; Chan, Alice; Sareddy, Gangadhara Reddy; Vadlamudi, Ratna K.; Brann, Darrell W.

    2014-01-01

    17β-estradiol (E2) has been implicated to play a critical role in neuroprotection, synaptic plasticity, and cognitive function. Classically, the role of gonadal-derived E2 in these events is well established, but the role of brain-derived E2 is less clear. To address this issue, we investigated the expression, localization, and modulation of aromatase and local E2 levels in the hippocampus following global cerebral ischemia (GCI) in adult ovariectomized rats. Immunohistochemistry (IHC) revealed that the hippocampal regions CA1, CA3 and dentate gyrus (DG) exhibited high levels of immunoreactive aromatase staining, with aromatase being co-localized primarily in neurons in non-ischemic animals. Following GCI, aromatase became highly expressed in GFAP-positive astrocytes in the hippocampal CA1 region at 2–3 days post GCI reperfusion. An ELISA for E2 and IHC for E2 confirmed the GCI-induced elevation of local E2 in the CA1 region and that the increase in local E2 occurred in astrocytes. Furthermore, central administration of aromatase antisense (AS) oligonucleotides, but not missense (MS) oligonucleotides, blocked the increase in aromatase and local E2 in astrocytes after GCI, and resulted in a significant increase in GCI-induced hippocampal CA1 region neuronal cell death and neuroinflammation. As a whole, these results suggest that brain-derived E2 exerts important neuroprotective and anti-inflammatory actions in the hippocampal CA1 region following GCI. PMID:24508637

  19. RNA-seq analysis of developing olfactory bulb projection neurons.

    PubMed

    Kawasawa, Yuka Imamura; Salzberg, Anna C; Li, Mingfeng; Šestan, Nenad; Greer, Charles A; Imamura, Fumiaki

    2016-07-01

    Transmission of olfactory information to higher brain regions is mediated by olfactory bulb (OB) projection neurons, the mitral and tufted cells. Although mitral/tufted cells are often characterized as the OB counterpart of cortical projection neurons (also known as pyramidal neurons), they possess several unique morphological characteristics and project specifically to the olfactory cortices. Moreover, the molecular networks contributing to the generation of mitral/tufted cells during development are largely unknown. To understand the developmental patterns of gene expression in mitral/tufted cells in the OB, we performed transcriptome analyses targeting purified OB projection neurons at different developmental time points with next-generation RNA sequencing (RNA-seq). Through these analyses, we found 1202 protein-coding genes that are temporally differentially-regulated in developing projection neurons. Among them, 388 genes temporally changed their expression level only in projection neurons. The data provide useful resource to study the molecular mechanisms regulating development of mitral/tufted cells. We further compared the gene expression profiles of developing mitral/tufted cells with those of three cortical projection neuron subtypes, subcerebral projection neurons, corticothalamic projection neurons, and callosal projection neurons, and found that the molecular signature of developing olfactory projection neuron bears resemblance to that of subcerebral neurons. We also identified 3422 events that change the ratio of splicing isoforms in mitral/tufted cells during maturation. Interestingly, several genes expressed a novel isoform not previously reported. These results provide us with a broad perspective of the molecular networks underlying the development of OB projection neurons. PMID:27073125

  20. Spatiotemporal properties of fast and slow neurons in the pretectal nucleus lentiformis mesencephali in pigeons.

    PubMed

    Wylie, D R; Crowder, N A

    2000-11-01

    Neurons in the pretectal nucleus lentiformis mesencephali (LM) are involved in the analysis of optic flow that results from self-motion. Previous studies have shown that LM neurons have large receptive fields in the contralateral eye, are excited in response to largefield stimuli moving in a particular (preferred) direction, and are inhibited in response to motion in the opposite (anti-preferred) direction. We investigated the responses of LM neurons to sine wave gratings of varying spatial and temporal frequency drifting in the preferred and anti-preferred directions. The LM neurons fell into two categories. "Fast" neurons were maximally excited by gratings of low spatial [0.03-0.25 cycles/ degrees (cpd)] and mid-high temporal frequencies (0.5-16 Hz). "Slow" neurons were maximally excited by gratings of high spatial (0.35-2 cpd) and low-mid temporal frequencies (0.125-2 Hz). Of the slow neurons, all but one preferred forward (temporal to nasal) motion. The fast group included neurons that preferred forward, backward, upward, and downward motion. For most cells (81%), the spatial and temporal frequency that elicited maximal excitation to motion in the preferred direction did not coincide with the spatial and temporal frequency that elicited maximal inhibition to gratings moving in the anti-preferred direction. With respect to motion in the anti-preferred direction, a substantial proportion of the LM neurons (32%) showed bi-directional responses. That is, the spatiotemporal plots contained domains of excitation in addition to the region of inhibition. Neurons tuned to stimulus velocity across different spatial frequency were rare (5%), but some neurons (39%) were tuned to temporal frequency. These results are discussed in relation to previous studies of the responses of neurons in the accessory optic system and pretectum to drifting gratings and other largefield stimuli. PMID:11067995

  1. 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

  2. Neuronal variability of MSTd neurons changes differentially with eye movement and visually related variables.

    PubMed

    Brostek, Lukas; Büttner, Ulrich; Mustari, Michael J; Glasauer, Stefan

    2013-08-01

    Neurons in macaque cortical area MSTd are driven by visual motion and eye movement related signals. This multimodal characteristic makes MSTd an ideal system for studying the dependence of neuronal activity on different variables. Here, we analyzed the temporal structure of spiking patterns during visual motion stimulation using 2 distinct behavioral paradigms: fixation (FIX) and optokinetic response. For the FIX condition, inter- and intra-trial variability of spiking activity decreased with increasing stimulus strength, complying with a recent neurophysiological study reporting stimulus-related decline of neuronal variability. In contrast, for the optokinetic condition variability increased together with increasing eye velocity while retinal image velocity remained low. Analysis of stimulus signal variability revealed a correlation between the normalized variance of image velocity and neuronal variability, but no correlation with normalized eye velocity variance. We further show that the observed difference in neuronal variability allows classifying spike trains according to the paradigm used, even when mean firing rates (FRs) were similar. The stimulus-dependence of neuronal variability may result from the local network structure and/or the variability characteristics of the input signals, but may also reflect additional timing-based mechanisms independent of the neuron's mean FR and related to the modality driving the neuron. PMID:22772648

  3. 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. PMID:26168436

  4. 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…

  5. 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…

  6. Chronic exertional compartment syndrome in adductor pollicis muscle: case report.

    PubMed

    Lee, Chang-Hun; Lee, Kwang-Hyun; Lee, Seung-Hun; Kim, Yee-Suk; Chung, Ung-Seo

    2012-11-01

    We report a case of chronic exertional compartment syndrome in the adductor pollicis that was confirmed by measuring elevated compartment pressure. Specific finding of magnetic resonance imaging, increased T2 signal intensity in the involved compartment, was also useful for the diagnosis. Pain was relieved by fasciotomy through a volar approach. PMID:23040640

  7. 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)

  8. Control of Phasic Firing by a Background Leak Current in Avian Forebrain Auditory Neurons.

    PubMed

    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

  9. 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

  10. 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. PMID:25201176

  11. Temporal Lobe Sclerosis Associated with Hippocampal Sclerosis in Temporal Lobe Epilepsy: Neuropathological Features

    PubMed Central

    Thom, Maria; Eriksson, Sofia; Martinian, Lillian; Caboclo, Luis O.; McEvoy, Andrew W.; Duncan, John S.; Sisodiya, Sanjay M.

    2009-01-01

    Widespread changes involving neocortical as well as mesial temporal lobe structures can be present in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). The incidence, pathology and clinical significance of neocortical temporal lobe sclerosis (TLS) are not well characterized. We identified TLS in 30 out of 272 surgically treated cases of HS. TLS was defined by variable reduction of neurons from cortical layers II/III and laminar gliosis; it was typically accompanied by additional architectural abnormalities of layer II, i.e. abnormal neuronal orientation and aggregation. Quantitative analysis including tessellation methods for the distribution of layer II neurons supported these observations. In 40% of cases there was a gradient of TLS with more severe involvement towards the temporal pole, possibly signifying involvement of hippocampal projection pathways. There was a history of a febrile seizure as an initial precipitating injury in 73% of patients with TLS compared to 36% without TLS; no other clinical differences TLS and non-TLS cases were identified. TLS was not evident pre-operatively by neuroimaging. No obvious effect of TLS on seizure outcome was noted after temporal lobe resection; 73% became seizure-free at 2 year follow up. In conclusion, approximately 11% of surgically treated HS is accompanied by TLS. TLS is likely an acquired process with accompanying re-organizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity. PMID:19606061

  12. 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

  13. The Role and Effects of ANXA1 in Temporal Lobe Epilepsy: A Protection Mechanism?

    PubMed Central

    Yao, Bao-zhen; Yu, Shi-qian; Yuan, Hao; Zhang, Hai-ju; Niu, Ping; Ye, Jing-ping

    2015-01-01

    Background The endogenous protein annexin A1 (ANXA1) is an anti-inflammatory mediator in the brain that is thought to contribute to the progression of many neurological conditions. However, its exact role in temporal lobe epilepsy (TLE) remains unclear. We hypothesized that ANXA1 exerts negative actions on TLE by alleviating inflammatory damage in neurons. To identify the potential mechanism of TLE by assessing ANXA1 expression in TLE rats. Material/Methods TLE was induced in rats (n=70) via an intraperitoneal injection of lithium chloride (LiCl) and pilocarpine (PILO). The control group (n=10) received an injection of the equivalent amount of saline. ANXA1 expression was detected via immunohistochemistry and Western blotting. Results Successful establishment of the TLE model in rats resulted in epileptic seizures. ANXA1 was immunohistochemically detected as brownish yellow particles in the dentate gyrus and the CA1 region of the door zone; this expression was predominantly localized to the cytoplasm of glia rather than neurons. ANXA1 expression was stronger in TLE rats compared with the control group. ANXA1 expression in TLE was also assessed via Western blotting, and compared between groups at various time points. ANXA1 expression was significantly increased in the acute (the first 24 h) and chronic (after 1 month) phases (P<0.001) but significantly decreased during the recovery phase (72 h, 1 week, and 2 weeks) (P<0.001). These findings suggest that ANXA1 expression is correlated with TLE activity. Conclusions Our data suggest that ANXA1 plays an important role in TLE by alleviating inflammatory damage and protecting neurons. PMID:26609771

  14. Human occipital cortices differentially exert saccadic suppression: Intracranial recording in children.

    PubMed

    Uematsu, Mitsugu; Matsuzaki, Naoyuki; Brown, Erik C; Kojima, Katsuaki; Asano, Eishi

    2013-12-01

    By repeating saccades unconsciously, humans explore the surrounding world every day. Saccades inevitably move external visual images across the retina at high velocity; nonetheless, healthy humans don't perceive transient blurring of the visual scene during saccades. This perceptual stability is referred to as saccadic suppression. Functional suppression is believed to take place transiently in the visual systems, but it remains unknown how commonly or differentially the human occipital lobe activities are suppressed at the large-scale cortical network level. We determined the spatial-temporal dynamics of intracranially-recorded gamma activity at 80-150 Hz around spontaneous saccades under no-task conditions during wakefulness and those in darkness during REM sleep. Regardless of wakefulness or REM sleep, a small degree of attenuation of gamma activity was noted in the occipital regions during saccades, most extensively in the polar and least in the medial portions. Longer saccades were associated with more intense gamma-attenuation. Gamma-attenuation was subsequently followed by gamma-augmentation most extensively involving the medial and least involving the polar occipital region. Such gamma-augmentation was more intense during wakefulness and temporally locked to the offset of saccades. The polarities of initial peaks of perisaccadic event-related potentials (ERPs) were frequently positive in the medial and negative in the polar occipital regions. The present study, for the first time, provided the electrophysiological evidence that human occipital cortices differentially exert perisaccadic modulation. Transiently suppressed sensitivity of the primary visual cortex in the polar region may be an important neural basis for saccadic suppression. Presence of occipital gamma-attenuation even during REM sleep suggests that saccadic suppression might be exerted even without external visual inputs. The primary visual cortex in the medial region, compared to the polar

  15. Oscillatorylike behavior in feedforward neuronal networks

    NASA Astrophysics Data System (ADS)

    Payeur, Alexandre; Maler, Leonard; Longtin, André

    2015-07-01

    We demonstrate how rhythmic activity can arise in neural networks from feedforward rather than recurrent circuitry and, in so doing, we provide a mechanism capable of explaining the temporal decorrelation of γ -band oscillations. We compare the spiking activity of a delayed recurrent network of inhibitory neurons with that of a feedforward network with the same neural properties and axonal delays. Paradoxically, these very different connectivities can yield very similar spike-train statistics in response to correlated input. This happens when neurons are noisy and axonal delays are short. A Taylor expansion of the feedback network's susceptibility—or frequency-dependent gain function—can then be stopped at first order to a good approximation, thus matching the feedforward net's susceptibility. The feedback network is known to display oscillations; these oscillations imply that the spiking activity of the population is felt by all neurons within the network, leading to direct spike correlations in a given neuron. On the other hand, in the output layer of the feedforward net, the interaction between the external drive and the delayed feedforward projection of this drive by the input layer causes indirect spike correlations: spikes fired by a given output layer neuron are correlated only through the activity of the input layer neurons. High noise and short delays partially bridge the gap between these two types of correlation, yielding similar spike-train statistics for both networks. This similarity is even stronger when the delay is distributed, as confirmed by linear response theory.

  16. Oscillatorylike behavior in feedforward neuronal networks.

    PubMed

    Payeur, Alexandre; Maler, Leonard; Longtin, André

    2015-07-01

    We demonstrate how rhythmic activity can arise in neural networks from feedforward rather than recurrent circuitry and, in so doing, we provide a mechanism capable of explaining the temporal decorrelation of γ-band oscillations. We compare the spiking activity of a delayed recurrent network of inhibitory neurons with that of a feedforward network with the same neural properties and axonal delays. Paradoxically, these very different connectivities can yield very similar spike-train statistics in response to correlated input. This happens when neurons are noisy and axonal delays are short. A Taylor expansion of the feedback network's susceptibility-or frequency-dependent gain function-can then be stopped at first order to a good approximation, thus matching the feedforward net's susceptibility. The feedback network is known to display oscillations; these oscillations imply that the spiking activity of the population is felt by all neurons within the network, leading to direct spike correlations in a given neuron. On the other hand, in the output layer of the feedforward net, the interaction between the external drive and the delayed feedforward projection of this drive by the input layer causes indirect spike correlations: spikes fired by a given output layer neuron are correlated only through the activity of the input layer neurons. High noise and short delays partially bridge the gap between these two types of correlation, yielding similar spike-train statistics for both networks. This similarity is even stronger when the delay is distributed, as confirmed by linear response theory. PMID:26274199

  17. 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. PMID:26464042

  18. 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

  19. 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.

  20. 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

  1. Endoscopic Thermal Fasciotomy for Chronic Exertional Compartment Syndrome.

    PubMed

    Voleti, Pramod B; Lebrun, Drake G; Roth, Cameron A; Kelly, John D

    2015-10-01

    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

  2. Influence of pressure exerted on the sclera during transscleral cyclophotocoagulation

    NASA Astrophysics Data System (ADS)

    Rol, Pascal O.; Fankhauser, Franz, Jr.; Niederer, Peter F.

    1993-06-01

    Since its introduction in 1973 by Beckmann et al., transscleral cyclophotocoagulation with the Nd:YAG laser has developed into a successful method in glaucoma therapy. It was initially performed with the aid of non-contact systems, whereby the laser beam was focused by means of a slit lamp. With the introduction of contact systems, for which purpose a number of different probes were employed, the treatment efficiency was found to be improved by a factor between 2 to 6. The transparency of the sclera increases as a function of the pressure exerted. Therefore, the pressure exerted by the contact probe is a critical factor in determining the transmission of laser radiation across the sclera and may in part explain the large differences which are reported in the literature with respect to the effectiveness of this treatment method.

  3. 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.

  4. Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation.

    PubMed

    Fröhlich, Dominik; Kuo, Wen Ping; Frühbeis, Carsten; Sun, Jyh-Jang; Zehendner, Christoph M; Luhmann, Heiko J; Pinto, Sheena; Toedling, Joern; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

    2014-09-26

    Exosomes are small membranous vesicles of endocytic origin that are released by almost every cell type. They exert versatile functions in intercellular communication important for many physiological and pathological processes. Recently, exosomes attracted interest with regard to their role in cell-cell communication in the nervous system. We have shown that exosomes released from oligodendrocytes upon stimulation with the neurotransmitter glutamate are internalized by neurons and enhance the neuronal stress tolerance. Here, we demonstrate that oligodendroglial exosomes also promote neuronal survival during oxygen-glucose deprivation, a model of cerebral ischaemia. We show the transfer from oligodendrocytes to neurons of superoxide dismutase and catalase, enzymes which are known to help cells to resist oxidative stress. Additionally, we identify various effects of oligodendroglial exosomes on neuronal physiology. Electrophysiological analysis using in vitro multi-electrode arrays revealed an increased firing rate of neurons exposed to oligodendroglial exosomes. Moreover, gene expression analysis and phosphorylation arrays uncovered differentially expressed genes and altered signal transduction pathways in neurons after exosome treatment. Our study thus provides new insight into the broad spectrum of action of oligodendroglial exosomes and their effects on neuronal physiology. The exchange of extracellular vesicles between neural cells may exhibit remarkable potential to impact brain performance. PMID:25135971

  5. Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation

    PubMed Central

    Fröhlich, Dominik; Kuo, Wen Ping; Frühbeis, Carsten; Sun, Jyh-Jang; Zehendner, Christoph M.; Luhmann, Heiko J.; Pinto, Sheena; Toedling, Joern; Trotter, Jacqueline; Krämer-Albers, Eva-Maria

    2014-01-01

    Exosomes are small membranous vesicles of endocytic origin that are released by almost every cell type. They exert versatile functions in intercellular communication important for many physiological and pathological processes. Recently, exosomes attracted interest with regard to their role in cell–cell communication in the nervous system. We have shown that exosomes released from oligodendrocytes upon stimulation with the neurotransmitter glutamate are internalized by neurons and enhance the neuronal stress tolerance. Here, we demonstrate that oligodendroglial exosomes also promote neuronal survival during oxygen–glucose deprivation, a model of cerebral ischaemia. We show the transfer from oligodendrocytes to neurons of superoxide dismutase and catalase, enzymes which are known to help cells to resist oxidative stress. Additionally, we identify various effects of oligodendroglial exosomes on neuronal physiology. Electrophysiological analysis using in vitro multi-electrode arrays revealed an increased firing rate of neurons exposed to oligodendroglial exosomes. Moreover, gene expression analysis and phosphorylation arrays uncovered differentially expressed genes and altered signal transduction pathways in neurons after exosome treatment. Our study thus provides new insight into the broad spectrum of action of oligodendroglial exosomes and their effects on neuronal physiology. The exchange of extracellular vesicles between neural cells may exhibit remarkable potential to impact brain performance. PMID:25135971

  6. Exerting control and adapting to loss in amyotrophic lateral sclerosis.

    PubMed

    Foley, Geraldine; Timonen, Virpi; Hardiman, Orla

    2014-01-01

    People with amyotrophic lateral sclerosis (ALS) engage with a broad range of health care services from symptom onset to end-of-life care. We undertook a grounded theory study to identify processes that underpin how and why people with ALS engage with health care services. Using theoretical sampling procedures, we sampled 34 people from the Irish ALS population-based register during September 2011 to August 2012. We conducted in-depth interviews with participants about their experiences of health care services. Our study yielded new insights into how people with ALS engage with services and adapt to loss. People with ALS live with insurmountable loss and never regain what they have already lost. Loss for people with ALS is multidimensional and includes loss of control. The experience of loss of control prompts people with ALS to search for control over health care services but exerting control in health care services can also include rendering control to service providers. People with ALS negotiate loss by exerting control over and rendering control to health care services. Our findings are important for future research that is attuned to how people with terminal illness exert control in health care services and make decisions about care in the context of mounting loss. PMID:24560231

  7. 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. PMID:23906116

  8. 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

  9. The concept of temporal 'plus' epilepsy.

    PubMed

    Kahane, P; Barba, C; Rheims, S; Job-Chapron, A S; Minotti, L; Ryvlin, P

    2015-03-01

    The concept of temporal 'plus' epilepsy (T+E) is not new, and a number of observations made by means of intracerebral electrodes have illustrated the complexity of neuronal circuits that involve the temporal lobe. The term T+E was used to unify and better individualize these specific forms of multilobar epilepsies, which are characterized by electroclinical features primarily suggestive of temporal lobe epilepsy, MRI findings that are either unremarkable or show signs of hippocampal sclerosis, and intracranial recordings which demonstrate that seizures arise from a complex epileptogenic network including a combination of brain regions located within the temporal lobe and over closed neighbouring structures such as the orbitofrontal cortex, the insulo-opercular region, and the temporo-parieto-occipital junction. We will review here how the term of T+E has emerged, what it means, and which practical consideration it raises. PMID:25748333

  10. Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures.

    PubMed

    Tian, Yuan-Yuan; An, Li-Jia; Jiang, Lan; Duan, Yan-Long; Chen, Jun; Jiang, Bo

    2006-12-23

    Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Microglia, the resident immune cells in the central nervous system, are pivotal in the inflammatory reaction. Activated microglia can induce expression of inducible nitric-oxide synthase (iNOS) and release significant amounts of nitric oxide (NO) and TNF-alpha, which can damage the dopaminergic neurons. Catalpol, an iridoid glycoside, contained richly in the roots of Rehmannia glutinosa, was found to be neuroprotective in gerbils subjected to transient global cerebral ischemia. But the effect of catalpol on inflammation-mediated neurodegeneration has not been examined. In this study, microglia in mesencephalic neuron-glia cultures were activated with lipopolysaccharide (LPS) and the aim of the study was to examine whether catalpol could protect dopaminergic neurons from LPS-induced neurotoxicity. The results showed that catalpol significantly reduced the release of reactive oxygen species (ROS), TNF-alpha and NO after LPS-induced microglial activation. Further, catalpol attenuated LPS-induced the expression of iNOS. As determined by immunocytochemical analysis, pretreatment by catalpol dose-dependently protected dopaminergic neurons against LPS-induced neurotoxicity. These results suggest that catalpol exerts its protective effect on dopaminergic neurons by inhibiting microglial activation and reducing the production of proinflammatory factors. Thus, catalpol may possess therapeutic potential against inflammation-related neurodegenerative diseases. PMID:17049947

  11. Target cell-specific modulation of neuronal activity by astrocytes

    NASA Astrophysics Data System (ADS)

    Kozlov, A. S.; Angulo, M. C.; Audinat, E.; Charpak, S.

    2006-06-01

    Interaction between astrocytes and neurons enriches the behavior of brain circuits. By releasing glutamate and ATP, astrocytes can directly excite neurons and modulate synaptic transmission. In the rat olfactory bulb, we demonstrate that the release of GABA by astrocytes causes long-lasting and synchronous inhibition of mitral and granule cells. In addition, astrocytes release glutamate, leading to a selective activation of granule-cell NMDA receptors. Thus, by releasing excitatory and inhibitory neurotransmitters, astrocytes exert a complex modulatory control on the olfactory network. glutamate | GABA | inhibition | olfactory bulb | synchronization

  12. 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.

  13. Senegenin inhibits neuronal apoptosis after spinal cord contusion injury

    PubMed Central

    Zhang, Shu-quan; Wu, Min-fei; Gu, Rui; Liu, Jia-bei; Li, Ye; Zhu, Qing-san; Jiang, Jin-lan

    2016-01-01

    Senegenin has been shown to inhibit neuronal apoptosis, thereby exerting a neuroprotective effect. In the present study, we established a rat model of spinal cord contusion injury using the modified Allen's method. Three hours after injury, senegenin (30 mg/g) was injected into the tail vein for 3 consecutive days. Senegenin reduced the size of syringomyelic cavities, and it substantially reduced the number of apoptotic cells in the spinal cord. At the site of injury, Bax and Caspase-3 mRNA and protein levels were decreased by senegenin, while Bcl-2 mRNA and protein levels were increased. Nerve fiber density was increased in the spinal cord proximal to the brain, and hindlimb motor function and electrophysiological properties of rat hindlimb were improved. Taken together, our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury. PMID:27212931

  14. Senegenin inhibits neuronal apoptosis after spinal cord contusion injury.

    PubMed

    Zhang, Shu-Quan; Wu, Min-Fei; Gu, Rui; Liu, Jia-Bei; Li, Ye; Zhu, Qing-San; Jiang, Jin-Lan

    2016-04-01

    Senegenin has been shown to inhibit neuronal apoptosis, thereby exerting a neuroprotective effect. In the present study, we established a rat model of spinal cord contusion injury using the modified Allen's method. Three hours after injury, senegenin (30 mg/g) was injected into the tail vein for 3 consecutive days. Senegenin reduced the size of syringomyelic cavities, and it substantially reduced the number of apoptotic cells in the spinal cord. At the site of injury, Bax and Caspase-3 mRNA and protein levels were decreased by senegenin, while Bcl-2 mRNA and protein levels were increased. Nerve fiber density was increased in the spinal cord proximal to the brain, and hindlimb motor function and electrophysiological properties of rat hindlimb were improved. Taken together, our results suggest that senegenin exerts a neuroprotective effect by suppressing neuronal apoptosis at the site of spinal cord injury. PMID:27212931

  15. Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy

    PubMed Central

    RONG, ZHIHUI; PAN, RUI; CHANG, LIWEN; LEE, WEIHUA

    2015-01-01

    Neonatal hypoxic-ischemic (HI) brain injury causes severe brain damage in newborns. Following HI injury, rapidly accumulating oxidants injure neurons and interrupt ongoing developmental processes. The antioxidant, sodium pyruvate, has been shown to reduce neuronal injury in neonatal rats under conditions of oxygen glucose deprivation (OGD) and HI injury. In this study, we evaluated the effects of ethyl pyruvate (EP) and insulin-like growth factor-I (IGF-I) alone or in combination in a similar setting. For this purpose, we used an in vitro model involving primary neonatal rat cortical neurons subjected to OGD for 2.5 h and an in vivo model involving unilateral carotid ligation in rats on post-natal day 7 with exposure to 8% hypoxia for 2.5 h. The cultured neurons were examined by lactate dehydrogenase (LDH) and cell viability assays. For the in vivo experiments, behavioral development was evaluated by the foot fault test at 4 weeks of recovery. 2,3,5-Triphenyltetrazolium chloride monohydrate and cresyl violet staining were used to evaluate HI injury. The injured neurons were Fluoro-Jade B-labeled, new neuroprecursors were double labeled with bromodeoxyuridine (BrdU) and doublecortin, new mature neurons were BrdU-labeled and neuronal nuclei were labeled by immunofluorescence. Under conditions of OGD, the LDH levels increased and neuronal viability decreased. Treatment with 0.5 mM EP or 25 ng/ml IGF-I protected the neurons (P<0.05), exerting additive effects. Similarly, either the early administration of EP or delayed treatment with IGF-I protected the neonatal rat brains against HI injury and improved neurological performance and these effects were also additive. This effect may be the result of reduced neuronal injury, and enhanced neurogenesis and maturation. On the whole, our findings demonstrate that the combination of the early administration of EP with delayed treatment with IGF-I exerts neuroprotective effects against HI injury in neonatal rat brains. PMID

  16. Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

    PubMed

    Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

    2016-01-15

    The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. PMID:26681545

  17. 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 models of 6-hydroxydopamine (6-OH-DA)-induced degeneration. The in vivo model was based on the intrastriatal infusion of the neurotoxin 6-OH-DA, which generates Parkinsonian symptoms. Rats were treated 2 h before and after the 6-OH-DA treatment with systemic OEA (0.5, 1, and 5 mg/kg). The Parkinsonian symptoms were evaluated at 1 and 4 wk after the development of lesions. The functional status of the nigrostriatal system was studied through tyrosine-hydroxylase (TH) and hemeoxygenase-1 (HO-1, oxidation marker) immunostaining as well as by monitoring the synaptophysin content. In vitro cell cultures were also treated with OEA and 6-OH-DA. As expected, our results revealed 6-OH-DA induced neurotoxicity and behavioural deficits; however, these alterations were less severe in the animals treated with the highest dose of OEA (5 mg/kg). 6-OH-DA administration significantly reduced the striatal TH-immunoreactivity (ir) density, synaptophysin expression, and the number of nigral TH-ir neurons. Moreover, 6-OH-DA enhanced striatal HO-1 content, which was blocked by OEA (5 mg/kg). In vitro, 0.5 and 1 μM of OEA exerted significant neuroprotection on cultured nigral neurons. These effects were abolished after blocking PPARα with the selective antagonist GW6471. In conclusion, systemic OEA protects the nigrostriatal circuit from 6-OH-DA-induced neurotoxicity through a PPARα-dependent mechanism. PMID:24169105

  18. Network and neuronal membrane properties in hybrid networks reciprocally regulate selectivity to rapid thalamocortical inputs.

    PubMed

    Pesavento, Michael J; Pinto, David J

    2012-11-01

    Rapidly changing environments require rapid processing from sensory inputs. Varying deflection velocities of a rodent's primary facial vibrissa cause varying temporal neuronal activity profiles within the ventral posteromedial thalamic nucleus. Local neuron populations in a single somatosensory layer 4 barrel transform sparsely coded input into a spike count based on the input's temporal profile. We investigate this transformation by creating a barrel-like hybrid network with whole cell recordings of in vitro neurons from a cortical slice preparation, embedding the biological neuron in the simulated network by presenting virtual synaptic conductances via a conductance clamp. Utilizing the hybrid network, we examine the reciprocal network properties (local excitatory and inhibitory synaptic convergence) and neuronal membrane properties (input resistance) by altering the barrel population response to diverse thalamic input. In the presence of local network input, neurons are more selective to thalamic input timing; this arises from strong feedforward inhibition. Strongly inhibitory (damping) network regimes are more selective to timing and less selective to the magnitude of input but require stronger initial input. Input selectivity relies heavily on the different membrane properties of excitatory and inhibitory neurons. When inhibitory and excitatory neurons had identical membrane properties, the sensitivity of in vitro neurons to temporal vs. magnitude features of input was substantially reduced. Increasing the mean leak conductance of the inhibitory cells decreased the network's temporal sensitivity, whereas increasing excitatory leak conductance enhanced magnitude sensitivity. Local network synapses are essential in shaping thalamic input, and differing membrane properties of functional classes reciprocally modulate this effect. PMID:22896716

  19. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

    PubMed Central

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  20. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

    PubMed

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  1. 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. PMID:25277741

  2. Pressure exerted by a grafted polymer: Bethe lattice solution

    NASA Astrophysics Data System (ADS)

    Mynssem Brum, Rafael; Stilck, Jürgen F.

    2015-01-01

    We solve the problem of a chain, modeled as a self-avoiding walk (SAW), grafted to the wall limiting a semi-infinite Bethe lattice of arbitrary coordination number q. In particular, we determine the pressure exerted by the polymer on the wall, as a function of the distance to the grafting point. The pressure, in general, decays exponentially with the distance, at variance with what is found for SAWs and directed walks on regular lattices and gaussian walks. The adsorption transition, which is discontinuous, and its influence on the pressure are also studied.

  3. [Chronic exertional compartment syndrome in the lower leg].

    PubMed

    Hansen, Rasmus Lund; Jessen, Peter Toquer

    2015-01-01

    Chronic exertional compartment syndrome (CECS) commonly occurs in young adult runners. The mechanism of pain is unknown. CECS is a clinical diagnosis and is confirmed by intracompartmental pressure testing (IPT). The evidence-based guidance for IPT is sparse. Instead of Pedowitz et al's criteria we recommend one minute after pain triggered exercise IPT ≥ 36 mmHg as diagnostic value. At the moment fasciotomy is the treatment of choice for athletes who would like to maintain the same level of activity, but injection with botulinum toxin type A could be a new useful alternative. PMID:25557448

  4. Novel interfaces for light directed neuronal stimulation: advances and challenges

    PubMed Central

    Bareket-Keren, Lilach; Hanein, Yael

    2014-01-01

    Light activation of neurons is a growing field with applications ranging from basic investigation of neuronal systems to the development of new therapeutic methods such as artificial retina. Many recent studies currently explore novel methods for optical stimulation with temporal and spatial precision. Novel materials in particular provide an opportunity to enhance contemporary approaches. Here we review recent advances towards light directed interfaces for neuronal stimulation, focusing on state-of-the-art nanoengineered devices. In particular, we highlight challenges and prospects towards improved retinal prostheses. PMID:24872704

  5. A digital neuron-type processor and its VLSI design

    SciTech Connect

    Habib, M.K.; Akel, H. )

    1989-05-01

    A set of neuron-type circuits elements based on logic gate circuits with multi-input capability is described. Three types of elements are introduced, one called the cell body with its dendritic inputs and synaptic junction, another representing the axon base and finally the axon circuit. These three elements are cascaded to form a neuron type processing element. The circuit performs input temporal and spatial summation as well as thresholding. The entire neuron circuit is simulated and a design is given using VLSI techniques.

  6. Monitoring Spiking Activity of Many Individual Neurons in Invertebrate Ganglia

    PubMed Central

    Brandon, C.J.; Bruno, A.M.; Humphries, M.D.; Moore-Kochlacs, C.; Sejnowski, T.J.; Wang, J.; Hill, E.S.

    2015-01-01

    Optical recording with fast voltage sensitive dyes makes it possible, in suitable preparations, to simultaneously monitor the action potentials of large numbers of individual neurons. Here we describe methods for doing this, including considerations of different dyes and imaging systems, methods for correlating the optical signals with their source neurons, procedures for getting good signals, and the use of Independent Component Analysis for spike-sorting raw optical data into single neuron traces. These combined tools represent a powerful approach for large-scale recording of neural networks with high temporal and spatial resolution. PMID:26238051

  7. Selective IT neurons are selective along many dimensions.

    PubMed

    Zhivago, Kalathupiriyan A; Arun, S P

    2016-03-01

    Our visual abilities are unsurpassed because of a sophisticated code for objects located in the inferior temporal (IT) cortex. This code has remained a mystery because IT neurons show extremely diverse shape selectivity with no apparent organizing principle. Here, we show that there is an intrinsic component to selectivity in IT neurons. We tested IT neurons on distinct shapes and their parametric variations and asked whether neurons selective along one dimension were also selective along others. Selective neurons responded to fewer shapes and were narrowly tuned to local variations of these shapes, both along arbitrary morph lines and along variations in size, position, or orientation. For a subset of neurons, selective neurons were selective for both shape and texture. Finally, selective neurons were also more invariant in that they preserved their shape preferences across changes in size, position, and orientation. These observations indicate that there is an intrinsic constraint on the sharpness of tuning for the features coded by each IT neuron, making it always sharply tuned or always broadly tuned along all dimensions. We speculate that this may be an organizing principle throughout visual cortex. PMID:26823517

  8. Selective IT neurons are selective along many dimensions

    PubMed Central

    Zhivago, Kalathupiriyan A.

    2016-01-01

    Our visual abilities are unsurpassed because of a sophisticated code for objects located in the inferior temporal (IT) cortex. This code has remained a mystery because IT neurons show extremely diverse shape selectivity with no apparent organizing principle. Here, we show that there is an intrinsic component to selectivity in IT neurons. We tested IT neurons on distinct shapes and their parametric variations and asked whether neurons selective along one dimension were also selective along others. Selective neurons responded to fewer shapes and were narrowly tuned to local variations of these shapes, both along arbitrary morph lines and along variations in size, position, or orientation. For a subset of neurons, selective neurons were selective for both shape and texture. Finally, selective neurons were also more invariant in that they preserved their shape preferences across changes in size, position, and orientation. These observations indicate that there is an intrinsic constraint on the sharpness of tuning for the features coded by each IT neuron, making it always sharply tuned or always broadly tuned along all dimensions. We speculate that this may be an organizing principle throughout visual cortex. PMID:26823517

  9. Interplay activity-connectivity: Dynamics in patterned neuronal cultures

    NASA Astrophysics Data System (ADS)

    Tibau, E.; Bendiksen, Ch.; Teller, S.; Amigó, N.; Soriano, J.

    2013-01-01

    The ability of a neuronal tissue to efficiently process and transmit information depends on both the intrinsic dynamical properties of the neurons and the connectivity between them. One of the few experimental systems where one can vary the connectivity of a neuronal network in a control manner are neuronal cultures. Here we show that, by combining neuronal cultures with different pattering techniques, we can control and dictate the connectivity of neuronal networks. The emerging cultures are characterized by a rich spontaneous activity, but with some dynamical traits that can be ascribed to the underlying, engineered wiring architecture. Simple patterned cultures can be obtained by plating neurons onto predefined topographical molds, which guide neurons and connections through complex paths. In contrast to homogeneous cultures, characterized by an on/off behavior where all neurons fire in a short time window, patterned cultures show more complex spatio-temporal dynamics, and with varying propagation paths and velocities. Patterned cultures provide a valuable tool to understand not only the interplay activity-connectivity, but also aspects such as the emergence and maintenance of spontaneous activity, synchronization, or the presence of specific dynamic motifs.

  10. Feedforward and Feedback inhibition in Neostriatal GABAergic Spiny Neurons

    PubMed Central

    Tepper, James M.; Wilson, Charles J.; Koós, Tibor

    2008-01-01

    There are two distinct inhibitory GABAergic circuits in the neostriatum. The feedforward circuit consists of a relatively small population of GABAergic interneurons that receives excitatory input from the neocortex and exerts monosynaptic inhibition onto striatal spiny projection neurons. The feedback circuit comprises the numerous spiny projection neurons and their interconnections via local axon collaterals. This network has long been assumed to provide the majority of striatal GABAergic inhibition and to sharpen and shape striatal output through lateral inhibition, producing increased activity in the most strongly excited spiny cells at the expense of their less strongly excited neighbors. Recent results, mostly from recording experiments of synaptically connected pairs of neurons, have revealed that the two GABAergic circuits differ markedly in terms of the total number of synapses made by each, the strength of the postsynaptic response detected at the soma, the extent of presynaptic convergence and divergence and the net effect of the activation of each circuit on the postsynaptic activity of the spiny neuron. These data have revealed that the feedforward inhibition is powerful and widespread, with spiking in a single interneuron being capable of significantly delaying or even blocking the generation of spikes in a large number of postsynaptic spiny neurons. In contrast, the postsynaptic effects of spiking in a single presynaptic spiny neuron on postsynaptic spiny neurons are weak when measured at the soma, and unable to significantly affect spike timing or generation. Further, reciprocity of synaptic connections between spiny neurons is only rarely observed. These results suggest that the bulk of the fast inhibition that has the strongest effects on spiny neuron spike timing comes from the feedforward interneuronal system whereas the axon collateral feedback system acts principally at the dendrites to control local excitability as well as the overall level of

  11. Optogenetic pharmacology for control of native neuronal signaling proteins

    PubMed Central

    Kramer, Richard H; Mourot, Alexandre; Adesnik, Hillel

    2016-01-01

    The optical neuroscience revolution is transforming how we study neural circuits. By providing a precise way to manipulate endogenous neuronal signaling proteins, it also has the potential to transform our understanding of molecular neuroscience. Recent advances in chemical biology have produced light-sensitive compounds that photoregulate a wide variety of proteins underlying signaling between and within neurons. Chemical tools for optopharmacology include caged agonists and antagonists and reversibly photoswitchable ligands. These reagents act on voltage-gated ion channels and neurotransmitter receptors, enabling control of neuronal signaling with a high degree of spatial and temporal precision. By covalently attaching photoswitch molecules to genetically tagged proteins, the newly emerging methodology of optogenetic pharmacology allows biochemically precise control in targeted subsets of neurons. Now that the tools for manipulating endogenous neuronal signaling proteins are available, they can be implemented in vivo to enhance our understanding of the molecular bases of brain function and dysfunctions. PMID:23799474

  12. Noise and neuronal populations conspire to encode simple waveforms reliably

    NASA Technical Reports Server (NTRS)

    Parnas, B. R.

    1996-01-01

    Sensory systems rely on populations of neurons to encode information transduced at the periphery into meaningful patterns of neuronal population activity. This transduction occurs in the presence of intrinsic neuronal noise. This is fortunate. The presence of noise allows more reliable encoding of the temporal structure present in the stimulus than would be possible in a noise-free environment. Simulations with a parallel model of signal processing at the auditory periphery have been used to explore the effects of noise and a neuronal population on the encoding of signal information. The results show that, for a given set of neuronal modeling parameters and stimulus amplitude, there is an optimal amount of noise for stimulus encoding with maximum fidelity.

  13. Optogenetic pharmacology for control of native neuronal signaling proteins.

    PubMed

    Kramer, Richard H; Mourot, Alexandre; Adesnik, Hillel

    2013-07-01

    The optical neuroscience revolution is transforming how we study neural circuits. By providing a precise way to manipulate endogenous neuronal signaling proteins, it also has the potential to transform our understanding of molecular neuroscience. Recent advances in chemical biology have produced light-sensitive compounds that photoregulate a wide variety of proteins underlying signaling between and within neurons. Chemical tools for optopharmacology include caged agonists and antagonists and reversibly photoswitchable ligands. These reagents act on voltage-gated ion channels and neurotransmitter receptors, enabling control of neuronal signaling with a high degree of spatial and temporal precision. By covalently attaching photoswitch molecules to genetically tagged proteins, the newly emerging methodology of optogenetic pharmacology allows biochemically precise control in targeted subsets of neurons. Now that the tools for manipulating endogenous neuronal signaling proteins are available, they can be implemented in vivo to enhance our understanding of the molecular bases of brain function and dysfunctions. PMID:23799474

  14. Mesmerising mirror neurons.

    PubMed

    Heyes, Cecilia

    2010-06-01

    Mirror neurons have been hailed as the key to understanding social cognition. I argue that three currents of thought-relating to evolution, atomism and telepathy-have magnified the perceived importance of mirror neurons. When they are understood to be a product of associative learning, rather than an adaptation for social cognition, mirror neurons are no longer mesmerising, but they continue to raise important questions about both the psychology of science and the neural bases of social cognition. PMID:20167276

  15. Temporal Encoding in a Nervous System

    PubMed Central

    Aldworth, Zane N.; Dimitrov, Alexander G.; Cummins, Graham I.; Gedeon, Tomáš; Miller, John P.

    2011-01-01

    We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures. PMID:21573206

  16. Dorsal–Ventral Gradient for Neuronal Plasticity in the Embryonic Spinal Cord

    PubMed Central

    Pineda, Ricardo H.; Ribera, Angeles B.

    2008-01-01

    Within the developing Xenopus spinal cord, voltage-gated potassium (Kv) channel genes display different expression patterns, many of which occur in opposing dorsal–ventral gradients. Regional differences in Kv gene expression would predict different patterns of potassium current (IKv) regulation. However, during the first 24 h of postmitotic differentiation, all primary spinal neurons undergo a temporally coordinated upregulation of IKv density that shortens the duration of the action potential. Here, we tested whether spinal neurons demonstrate regional differences in IKv regulation subsequent to action potential maturation. We show that two types of neurons, I and II, can be identified in culture on the basis of biophysical and pharmacological properties of IKv and different firing patterns. Chronic increases in extracellular potassium, a signature of high neuronal activity, do not alter excitability properties of either neuron type. However, elevating extracellular potassium acutely after the period of action potential maturation leads to different changes in membrane properties of the two types of neurons. IKv of type I neurons gains sensitivity to the blocker XE991, whereas type II neurons increase IKv density and fire fewer action potentials. Moreover, by recording from neurons in vivo, we found that primary spinal neurons can be identified as either type I or type II. Type I neurons predominate in dorsal regions, whereas type II neurons localize to ventral regions. The findings reveal a dorsal–ventral gradient for IKv regulation and a novel form of neuronal plasticity in spinal cord neurons. PMID:18385340

  17. The Significance of Causally Coupled, Stable Neuronal Assemblies for the Psychological Time Arrow

    NASA Astrophysics Data System (ADS)

    Atmanspacher, Harald; Filk, Thomas; Scheingraber, Herbert

    2005-10-01

    Stable neuronal assemblies are generally regarded as neural correlates of mental representations. Their temporal sequence corresponds to the experience of a direction of time, sometimes called the psychological time arrow. We show that the stability of particular, biophysically motivated models of neuronal assemblies, called coupled map lattices, is supported by causal interactions among neurons and obstructed by non-causal or anti-causal interactions among neurons. This surprising relation between causality and stability suggests that those neuronal assemblies that are stable due to causal neuronal interactions, and thus correlated with mental representations, generate a psychological time arrow. Yet this impact of causal interactions among neurons on the directed sequence of mental representations does not rule out the possibility of mentally less efficacious non-causal or anti-causal interactions among neurons.

  18. Neuronal response impedance mechanism implementing cooperative networks with low firing rates and μs precision

    PubMed Central

    Vardi, Roni; Goldental, Amir; Marmari, Hagar; Brama, Haya; Stern, Edward A.; Sardi, Shira; Sabo, Pinhas; Kanter, Ido

    2015-01-01

    Realizations of low firing rates in neural networks usually require globally balanced distributions among excitatory and inhibitory links, while feasibility of temporal coding is limited by neuronal millisecond precision. We show that cooperation, governing global network features, emerges through nodal properties, as opposed to link distributions. Using in vitro and in vivo experiments we demonstrate microsecond precision of neuronal response timings under low stimulation frequencies, whereas moderate frequencies result in a chaotic neuronal phase characterized by degraded precision. Above a critical stimulation frequency, which varies among neurons, response failures were found to emerge stochastically such that the neuron functions as a low pass filter, saturating the average inter-spike-interval. This intrinsic neuronal response impedance mechanism leads to cooperation on a network level, such that firing rates are suppressed toward the lowest neuronal critical frequency simultaneously with neuronal microsecond precision. Our findings open up opportunities of controlling global features of network dynamics through few nodes with extreme properties. PMID:26124707

  19. Neuronal response impedance mechanism implementing cooperative networks with low firing rates and μs precision.

    PubMed

    Vardi, Roni; Goldental, Amir; Marmari, Hagar; Brama, Haya; Stern, Edward A; Sardi, Shira; Sabo, Pinhas; Kanter, Ido

    2015-01-01

    Realizations of low firing rates in neural networks usually require globally balanced distributions among excitatory and inhibitory links, while feasibility of temporal coding is limited by neuronal millisecond precision. We show that cooperation, governing global network features, emerges through nodal properties, as opposed to link distributions. Using in vitro and in vivo experiments we demonstrate microsecond precision of neuronal response timings under low stimulation frequencies, whereas moderate frequencies result in a chaotic neuronal phase characterized by degraded precision. Above a critical stimulation frequency, which varies among neurons, response failures were found to emerge stochastically such that the neuron functions as a low pass filter, saturating the average inter-spike-interval. This intrinsic neuronal response impedance mechanism leads to cooperation on a network level, such that firing rates are suppressed toward the lowest neuronal critical frequency simultaneously with neuronal microsecond precision. Our findings open up opportunities of controlling global features of network dynamics through few nodes with extreme properties. PMID:26124707

  20. Optogenetic Activation of Adenosine A2A Receptor Signaling in the Dorsomedial Striatopallidal Neurons Suppresses Goal-Directed Behavior.

    PubMed

    Li, Yan; He, Yan; Chen, Mozi; Pu, Zhilan; Chen, Li; Li, Ping; Li, Bo; Li, Haiyan; Huang, Zhi-Li; Li, Zhihui; Chen, Jiang-Fan

    2016-03-01

    The striatum has an essential role in neural control of instrumental behaviors by reinforcement learning. Adenosine A(2A) receptors (A(2A)Rs) are highly enriched in the striatopallidal neurons and are implicated in instrumental behavior control. However, the temporal importance of the A(2A)R signaling in relation to the reward and specific contributions of the striatopallidal A(2A)Rs in the dorsolateral striatum (DLS) and the dorsomedial striatum (DMS) to the control of instrumental learning are not defined. Here, we addressed temporal relationship and sufficiency of transient activation of optoA(2A)R signaling precisely at the time of the reward to the control of instrumental learning, using our newly developed rhodopsin-A2AR chimeras (optoA(2A)R). We demonstrated that transient light activation of optoA(2A)R signaling in the striatopallidal neurons in 'time-locked' manner with the reward delivery (but not random optoA(2A)R activation) was sufficient to change the animal's sensitivity to outcome devaluation without affecting the acquisition or extinction phases of instrumental learning. We further demonstrated that optogenetic activation of striatopallidal A(2A)R signaling in the DMS suppressed goal-directed behaviors, as focally genetic knockdown of striatopallidal A(2A)Rs in the DMS enhanced goal-directed behavior by the devaluation test. By contrast, optogenetic activation or focal AAV-Cre-mediated knockdown of striatopallidal A(2A)R in the DLS had relatively limited effects on instrumental learning. Thus, the striatopallidal A(2A)R signaling in the DMS exerts inhibitory and predominant control of goal-directed behavior by acting precisely at the time of reward, and may represent a therapeutic target to reverse abnormal habit formation that is associated with compulsive obsessive disorder and drug addiction. PMID:26216520

  1. National Athletic Trainers' Association Position Statement: Exertional Heat Illnesses

    PubMed Central

    Casa, Douglas J.; DeMartini, Julie K.; Bergeron, Michael F.; Csillan, Dave; Eichner, E. Randy; Lopez, Rebecca M.; Ferrara, Michael S.; Miller, Kevin C.; O'Connor, Francis; Sawka, Michael N.; Yeargin, Susan W.

    2015-01-01

    Objective  To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. Background  Certified athletic trainers recognize and treat athletes with EHIs, often in high-risk environments. Although the proper recognition and successful treatment strategies are well documented, EHIs continue to plague athletes, and exertional heat stroke remains one of the leading causes of sudden death during sport. The recommendations presented in this document provide athletic trainers and allied health providers with an integrated scientific and clinically applicable approach to the prevention, recognition, treatment of, and return-to-activity guidelines for EHIs. These recommendations are given so that proper recognition and treatment can be accomplished in order to maximize the safety and performance of athletes. Recommendations  Athletic trainers and other allied health care professionals should use these recommendations to establish onsite emergency action plans for their venues and athletes. The primary goal of athlete safety is addressed through the appropriate prevention strategies, proper recognition tactics, and effective treatment plans for EHIs. Athletic trainers and other allied health care professionals must be properly educated and prepared to respond in an expedient manner to alleviate symptoms and minimize the morbidity and mortality associated with these illnesses. PMID:26381473

  2. Weight loss reduces dyspnea on exertion in obese women.

    PubMed

    Bernhardt, Vipa; Babb, Tony G

    2014-12-01

    During submaximal exercise, some otherwise healthy obese women experience breathlessness, or dyspnea on exertion (+DOE), while others have mild or no DOE (-DOE). We investigated whether weight loss could reduce DOE. Twenty nine obese women were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60 W cycling: +DOE (n = 14, RPB ≥ 4, 34 ± 8 years, and 36 ± 3 kg/m(2)) and -DOE ( n= 15, RPB ≤ 2, 32 ± 8 years, and 36 ± 4 kg/m(2)) and then completed a 12-week weight loss program. Both groups lost a moderate amount of weight (+DOE: 6.6 ± 2.4 kg, -DOE: 8.4 ± 3.5 kg, and p < 0.001). RPB decreased significantly in the +DOE group (from 4.7 ± 1.1 to 3.1 ± 1.6) and remained low in the -DOE (from 1.5 ± 0.7 to 1.6 ± 1.1) (interaction p < 0.002). Most physiological variables measured (i.e. body composition, fat distribution, pulmonary function, oxygen cost of breathing, and cardiorespiratory measures) improved with weight loss; however, the decrease in RPB was not correlated with any of these variables (p > 0.05). In conclusion, moderate weight loss was effective in reducing breathlessness on exertion in obese women who experienced DOE at baseline. PMID:25220695

  3. Severe physical exertion, oxidative stress, and acute lung injury.

    PubMed

    Shah, Nikunj R; Iqbal, M Bilal; Barlow, Andrew; Bayliss, John

    2011-11-01

    We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise-induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting. PMID:22064719

  4. Radiation torque exerted on a spheroid: Analytical solution

    NASA Astrophysics Data System (ADS)

    Xu, Feng; Lock, James A.; Gouesbet, Gérard; Tropea, Cameron

    2008-07-01

    As a companion work to our previous study [F. Xu, , Phys. Rev. E. 75, 026613 (2007)] on radiation force prediction for a homogeneous spheroid, we provide in this paper the analytical solution to the radiation torque exerted by an arbitrarily shaped beam on a spheroid, which can be prolate or oblate, transparent or absorbing. Calculations based upon this theoretical development are performed for both linearly and circularly polarized incident beams, and the results are compared to those of a sphere. Stable orientations of spheroids inside a linearly and a circularly polarized Gaussian beam are predicted. We analyze two physical mechanisms, the polarization torque and the reaction force torque, which do not exist or have no contribution to the torque on a sphere but cause rotation of a spheroid. As verification, the dipole method is also developed for the torque calculation for spheroids of size much less than the wavelength, and geometrical optics is developed to qualitatively analyze the torque exerted on spheroids of large size.

  5. Chronic Exertional Compartment Syndrome in a High School Soccer Player.

    PubMed

    Bresnahan, James J; Hennrikus, William L

    2015-01-01

    Chronic exertional compartment syndrome (CECS) is a relatively rare condition that affects young adult athletes and often causes them to present to the emergency department. If left untreated, those who continue to compete at high levels may experience debilitating leg pain. Physicians may have difficulty differentiating CECS from other syndromes of the lower leg such as medial tibial stress syndrome, stress fractures, and popliteal artery entrapment. The gold standard for diagnosing CECS is intramuscular compartment pressure monitoring before and/or after 10 minutes of exercise. Some patients may choose to stop participation in sports in order to relieve their pain, which otherwise does not respond well to nonoperative treatments. In patients who wish to continue to participate in sports and live an active life, fasciotomy provides relief in 80% or more. The typical athlete can return to training in about 8 weeks. This is a case of a high school soccer player who stopped competing due to chronic exertional compartment syndrome. She had a fascial hernia, resting intramuscular pressure of 30 mmHg, and postexercise intramuscular pressure of 99 mmHg. Following fasciotomy she experienced considerable life improvement and is once again training and playing soccer without symptoms. PMID:26229700

  6. Endoscopic compartment release for chronic exertional compartment syndrome.

    PubMed

    Knight, Justin R; Daniels, Marissa; Robertson, William

    2013-05-01

    Exertional compartment syndrome of the leg is a condition that can cause chronic debilitating pain in active persons during a variety of aerobic activities. Nonoperative treatments using stretching protocols and activity modifications are often unsuccessful, and thus several operative strategies have been used to treat this condition. A novel technique for endoscopically assisted fasciotomy for chronic exertional compartment syndrome is described. By use of a small laterally based incision and an arthroscope, polydioxanone sutures are passed percutaneously along the anterior and lateral compartments with the Spectrum suture-shuttling device (ConMed Linvatec, Largo, FL). These sutures are used to retract the skin and subcutaneous tissues over the respective compartments. This method allows excellent visualization of the intercompartmental septum, the superficial peroneal nerve, and all perforating vessels. The anterior and lateral compartments can be safely and completely released with this minimally invasive approach. The patient is allowed to return to full activity at 6 weeks postoperatively, because of the decreased soft-tissue disruption. PMID:23875149

  7. Endoscopic Compartment Release for Chronic Exertional Compartment Syndrome

    PubMed Central

    Knight, Justin R.; Daniels, Marissa; Robertson, William

    2013-01-01

    Exertional compartment syndrome of the leg is a condition that can cause chronic debilitating pain in active persons during a variety of aerobic activities. Nonoperative treatments using stretching protocols and activity modifications are often unsuccessful, and thus several operative strategies have been used to treat this condition. A novel technique for endoscopically assisted fasciotomy for chronic exertional compartment syndrome is described. By use of a small laterally based incision and an arthroscope, polydioxanone sutures are passed percutaneously along the anterior and lateral compartments with the Spectrum suture-shuttling device (ConMed Linvatec, Largo, FL). These sutures are used to retract the skin and subcutaneous tissues over the respective compartments. This method allows excellent visualization of the intercompartmental septum, the superficial peroneal nerve, and all perforating vessels. The anterior and lateral compartments can be safely and completely released with this minimally invasive approach. The patient is allowed to return to full activity at 6 weeks postoperatively, because of the decreased soft-tissue disruption. PMID:23875149

  8. Chronic Exertional Compartment Syndrome in a High School Soccer Player

    PubMed Central

    Bresnahan, James J.; Hennrikus, William L.

    2015-01-01

    Chronic exertional compartment syndrome (CECS) is a relatively rare condition that affects young adult athletes and often causes them to present to the emergency department. If left untreated, those who continue to compete at high levels may experience debilitating leg pain. Physicians may have difficulty differentiating CECS from other syndromes of the lower leg such as medial tibial stress syndrome, stress fractures, and popliteal artery entrapment. The gold standard for diagnosing CECS is intramuscular compartment pressure monitoring before and/or after 10 minutes of exercise. Some patients may choose to stop participation in sports in order to relieve their pain, which otherwise does not respond well to nonoperative treatments. In patients who wish to continue to participate in sports and live an active life, fasciotomy provides relief in 80% or more. The typical athlete can return to training in about 8 weeks. This is a case of a high school soccer player who stopped competing due to chronic exertional compartment syndrome. She had a fascial hernia, resting intramuscular pressure of 30 mmHg, and postexercise intramuscular pressure of 99 mmHg. Following fasciotomy she experienced considerable life improvement and is once again training and playing soccer without symptoms. PMID:26229700

  9. 3-Hydroxykynurenine: an intriguing molecule exerting dual actions in the central nervous system.

    PubMed

    Colín-González, Ana Laura; Maldonado, Perla D; Santamaría, Abel

    2013-01-01

    Kynurenine pathway is gaining attention due to the many metabolic processes in which it has been involved. The tryptophan conversion into several other metabolites through this pathway provides neuronal and redox modulators useful for maintenance of major functions in the brain. However, when physiopathological conditions prevail - i.e. oxidative stress, excitotoxicity, and inflammation - preferential formation and accumulation of toxic metabolites could trigger factors for degeneration in neurological disorders. 3-Hydroxykynurenine has been largely described as one of these toxic metabolites capable of inducing oxidative damage and cell death; consequently, this metabolite has been hypothesized to play a pivotal role in different neurological and psychiatric disorders. Supporting evidence has shown altered 3-hydroxykynurenine levels in samples of patients from several disorders. In contrast, some experimental studies have provided evidence of antioxidant and scavenging properties inherent to this molecule. In this review, we explored most of literature favoring one or the other concept, in order to provide an accurate vision on the real participation of this tryptophan metabolite in both experimental paradigms and human brain pathologies. Through this collected evidence, we provide an integrative hypothesis on how 3-hydroxykynurenine is exerting its dual actions in the central nervous system and what will be the course of investigations in this field for the next years. PMID:23219925

  10. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    PubMed Central

    Wichmann, Heidi; Brinkhoff, Thorsten; Simon, Meinhard; Richter-Landsberg, Christiane

    2016-01-01

    The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells. PMID:27164116

  11. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid.

    PubMed

    Wichmann, Heidi; Brinkhoff, Thorsten; Simon, Meinhard; Richter-Landsberg, Christiane

    2016-01-01

    The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells. PMID:27164116

  12. 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.

  13. Steroids as external temporal codes act via microRNAs and cooperate with cytokines in differential neurogenesis

    PubMed Central

    Kucherenko, Mariya M; Shcherbata, Halyna R

    2013-01-01

    The generation of neuronal cell diversity is controlled by interdependent mechanisms, including cell intrinsic programs and environmental cues. During development, the astonishing variety of neurons is originated according to a precise timetable that is managed by a complex network of genes specifying individual types of neurons. Different neurons express specific sets of transcription factors, and they can be recognized by morphological characteristics and spatial localization, but, most importantly, they connect to each other and form functional units in a stereotyped fashion. This connectivity depends, mostly, on selective cell adhesion that is strictly regulated. While intrinsic factors specifying neuronal temporal identity have been extensively studied, an extrinsic temporal factor controlling neuronal temporal identity switch has not been shown. Our data demonstrate that pulses of steroid hormone act as a temporal cue to fine-tune neuronal cell differentiation. Here we also provide evidence that extrinsic JAK/STAT cytokine signaling acts as a spatial code in the process. Particularly, in Drosophila mushroom bodies, neuronal identity transition is controlled by steroid-dependent microRNAs that regulate spatially distributed cytokine-dependent signaling factors that in turn modulate cell adhesion. A new era of neuronal plasticity assessment via managing external temporal cues such as hormones and cytokines that specify individual types of neurons might open new possibilities for brain regenerative therapeutics. PMID:23839338

  14. Relationship of prefrontal connections to inhibitory systems in superior temporal areas in the rhesus monkey.

    PubMed

    Barbas, H; Medalla, M; Alade, O; Suski, J; Zikopoulos, B; Lera, P

    2005-09-01

    The prefrontal cortex selects relevant signals and suppresses irrelevant signals in behavior, as exemplified by its functional interaction with superior temporal cortices. We addressed the structural basis of this process by investigating quantitatively the relationship of prefrontal pathways to inhibitory interneurons in superior temporal cortices. Pathways were labeled with neural tracers, and two neurochemical classes of inhibitory interneurons were labeled with parvalbumin (PV) and calbindin (CB), which differ in mode of inhibitory control. Both markers varied significantly and systematically across superior temporal areas. Calbindin neurons were more prevalent than PV neurons, with the highest densities found in posterior high-order auditory association cortices. Axons from anterior lateral, medial prefrontal and orbitofrontal areas terminated in the anterior half of the superior temporal gyrus, targeting mostly the superficial layers (I to upper III), where CB neurons predominated. Reciprocal projection neurons were intermingled with PV neurons, and emanated mostly from the deep part of layer III and to a lesser extent from layers V-VI, in proportions matching the laminar density of inhibitory interneurons. In marked contrast, prefrontal connections in temporal polar cortex were found mostly in the deep layers, showing mismatch with the predominant upper laminar distribution of interneurons. Differences in the relationship of connections to inhibitory neurons probably affect the dynamics in distinct superior temporal cortices. These findings may help explain the reduced efficacy of inhibitory control in superior temporal areas after prefrontal cortical damage. PMID:15635060

  15. Temporal Map Formation in the Barn Owl's Brain

    NASA Astrophysics Data System (ADS)

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

    2001-12-01

    Barn owls provide an experimentally well-specified example of a temporal map, a neuronal representation of the outside world in the brain by means of time. Their laminar nucleus exhibits a place code of interaural time differences, a cue which is used to determine the azimuthal location of a sound stimulus, e.g., prey. We analyze a model of synaptic plasticity that explains the formation of such a representation in the young bird and show how in a large parameter regime a combination of local and nonlocal synaptic plasticity yields the temporal map as found experimentally. Our analysis includes the effect of nonlinearities as well as the influence of neuronal noise.

  16. Direct Activation of Sleep-Promoting VLPO Neurons by Volatile Anesthetics Contributes to Anesthetic Hypnosis

    PubMed Central

    Moore, Jason T; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C; Beck, Sheryl G; Kelz, Max B

    2013-01-01

    Summary Background Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Results Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, while neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized, but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Conclusions Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. PMID:23103189

  17. Temporal spike pattern learning

    NASA Astrophysics Data System (ADS)

    Talathi, Sachin S.; Abarbanel, Henry D. I.; Ditto, William L.

    2008-09-01

    Sensory systems pass information about an animal’s environment to higher nervous system units through sequences of action potentials. When these action potentials have essentially equivalent wave forms, all information is contained in the interspike intervals (ISIs) of the spike sequence. How do neural circuits recognize and read these ISI sequences? We address this issue of temporal sequence learning by a neuronal system utilizing spike timing dependent plasticity (STDP). We present a general architecture of neural circuitry that can perform the task of ISI recognition. The essential ingredients of this neural circuit, which we refer to as “interspike interval recognition unit” (IRU) are (i) a spike selection unit, the function of which is to selectively distribute input spikes to downstream IRU circuitry; (ii) a time-delay unit that can be tuned by STDP; and (iii) a detection unit, which is the output of the IRU and a spike from which indicates successful ISI recognition by the IRU. We present two distinct configurations for the time-delay circuit within the IRU using excitatory and inhibitory synapses, respectively, to produce a delayed output spike at time t0+τ(R) in response to the input spike received at time t0 . R is the tunable parameter of the time-delay circuit that controls the timing of the delayed output spike. We discuss the forms of STDP rules for excitatory and inhibitory synapses, respectively, that allow for modulation of R for the IRU to perform its task of ISI recognition. We then present two specific implementations for the IRU circuitry, derived from the general architecture that can both learn the ISIs of a training sequence and then recognize the same ISI sequence when it is presented on subsequent occasions.

  18. Temporal spike pattern learning.

    PubMed

    Talathi, Sachin S; Abarbanel, Henry D I; Ditto, William L

    2008-09-01

    Sensory systems pass information about an animal's environment to higher nervous system units through sequences of action potentials. When these action potentials have essentially equivalent wave forms, all information is contained in the interspike intervals (ISIs) of the spike sequence. How do neural circuits recognize and read these ISI sequences? We address this issue of temporal sequence learning by a neuronal system utilizing spike timing dependent plasticity (STDP). We present a general architecture of neural circuitry that can perform the task of ISI recognition. The essential ingredients of this neural circuit, which we refer to as "interspike interval recognition unit" (IRU) are (i) a spike selection unit, the function of which is to selectively distribute input spikes to downstream IRU circuitry; (ii) a time-delay unit that can be tuned by STDP; and (iii) a detection unit, which is the output of the IRU and a spike from which indicates successful ISI recognition by the IRU. We present two distinct configurations for the time-delay circuit within the IRU using excitatory and inhibitory synapses, respectively, to produce a delayed output spike at time t_{0}+tau(R) in response to the input spike received at time t_{0} . R is the tunable parameter of the time-delay circuit that controls the timing of the delayed output spike. We discuss the forms of STDP rules for excitatory and inhibitory synapses, respectively, that allow for modulation of R for the IRU to perform its task of ISI recognition. We then present two specific implementations for the IRU circuitry, derived from the general architecture that can both learn the ISIs of a training sequence and then recognize the same ISI sequence when it is presented on subsequent occasions. PMID:18851076

  19. Responses of cockroach antennal lobe projection neurons to pulsatile olfactory stimuli.

    PubMed

    Lemon, W C; Getz, W M

    1998-11-30

    Behavioral evidence indicates that insects preferentially orient toward pulses of odorants as they occur downwind from a point source. Our recent results have shown that cockroach olfactory receptor neurons are able to reliably resolve 10-Hz pulses of the general "green' odorant 1-hexanol, but it is unknown to what extent the central olfactory pathway is able to resolve temporal aspects of a general odor stimulus. In the present study, temporal response characteristics were measured in antennal lobe projection neurons of female American cockroaches, Periplaneta americana in response to series of short odor pulses (2.5-20 Hz). Odor pulses were delivered to olfactory sensilla in a moving airstream controlled by electromagnetic valves and quantified by replacing the odorant with oil smoke and measuring the concentration of smoke passing through a light beam. The responses of projection neurons were recorded with an intracellular microelectrode placed in the projection neuron cell body. A variety of time courses of responses were recorded. Response patterns were consistent among identical stimuli within a neuron and varied among neurons. Some neurons increased spike frequency with stimulus onset while others decreased spike frequency. The latency to the change in spike frequency and the duration of the response also varied among neurons. Regardless of the temporal characteristics of the responses, nearly all projection neurons were able to resolve pulses of 1-hexanol presented at 5 Hz and some could resolve 10-Hz pulses. Thus, responses of antennal lobe projection neurons can reflect fine structures of non-uniform distributions of general odorants in a turbulent odor plume. In addition, the variety of temporal response characteristics to identical stimuli suggests that odor quality is coded by a temporal code expressed across a population of projection neurons. PMID:10049232

  20. An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity

    PubMed Central

    Sur, Mriganka

    2015-01-01

    Cholinergic modulation of cortex powerfully influences information processing and brain states, causing robust desynchronization of local field potentials and strong decorrelation of responses between neurons. Here we show that intracortical cholinergic inputs to mouse visual cortex specifically and differentially drive a defined cortical microcircuit: they facilitate somatostatin-expressing (SOM) inhibitory neurons that in turn inhibit parvalbumin-expressing inhibitory neurons and pyramidal neurons. Selective optogenetic inhibition of SOM responses blocks desynchronization and decorrelation, demonstrating that direct cholinergic activation of SOM neurons is necessary for this phenomenon. Optogenetic inhibition of vasoactive intestinal peptide-expressing neurons does not block desynchronization, despite these neurons being activated at high levels of cholinergic drive. Direct optogenetic SOM activation, independent of cholinergic modulation, is sufficient to induce desynchronization. Together, these findings demonstrate a mechanistic basis for temporal structure in cortical populations, and the crucial role of neuromodulatory drive to specific inhibitory-excitatory circuits in actively shaping the dynamics of neuronal activity. PMID:25915477

  1. An acetylcholine-activated microcircuit drives temporal dynamics of cortical activity.

    PubMed

    Chen, Naiyan; Sugihara, Hiroki; Sur, Mriganka

    2015-06-01

    Cholinergic modulation of cortex powerfully influences information processing and brain states, causing robust desynchronization of local field potentials and strong decorrelation of responses between neurons. We found that intracortical cholinergic inputs to mouse visual cortex specifically and differentially drive a defined cortical microcircuit: they facilitate somatostatin-expressing (SOM) inhibitory neurons that in turn inhibit parvalbumin-expressing inhibitory neurons and pyramidal neurons. Selective optogenetic inhibition of SOM responses blocked desynchronization and decorrelation, demonstrating that direct cholinergic activation of SOM neurons is necessary for this phenomenon. Optogenetic inhibition of vasoactive intestinal peptide-expressing neurons did not block desynchronization, despite these neurons being activated at high levels of cholinergic drive. Direct optogenetic SOM activation, independent of cholinergic modulation, was sufficient to induce desynchronization. Together, these findings demonstrate a mechanistic basis for temporal structure in cortical populations and the crucial role of neuromodulatory drive in specific inhibitory-excitatory circuits in actively shaping the dynamics of neuronal activity. PMID:25915477

  2. Behavioural correlates of combinatorial versus temporal features of odour codes.

    PubMed

    Saha, Debajit; Li, Chao; Peterson, Steven; Padovano, William; Katta, Nalin; Raman, Baranidharan

    2015-01-01

    Most sensory stimuli evoke spiking responses that are distributed across neurons and are temporally structured. Whether the temporal structure of ensemble activity is modulated to facilitate different neural computations is not known. Here, we investigated this issue in the insect olfactory system. We found that an odourant can generate synchronous or asynchronous spiking activity across a neural ensemble in the antennal lobe circuit depending on its relative novelty with respect to a preceding stimulus. Regardless of variations in temporal spiking patterns, the activated combinations of neurons robustly represented stimulus identity. Consistent with this interpretation, locusts reliably recognized both solitary and sequential introductions of trained odourants in a quantitative behavioural assay. However, predictable behavioural responses across locusts were observed only to novel stimuli that evoked synchronized spiking patterns across neural ensembles. Hence, our results indicate that the combinatorial ensemble response encodes for stimulus identity, whereas the temporal structure of the ensemble response selectively emphasizes novel stimuli. PMID:25912016

  3. Behavioural correlates of combinatorial versus temporal features of odour codes

    PubMed Central

    Saha, Debajit; Li, Chao; Peterson, Steven; Padovano, William; Katta, Nalin; Raman, Baranidharan

    2015-01-01

    Most sensory stimuli evoke spiking responses that are distributed across neurons and are temporally structured. Whether the temporal structure of ensemble activity is modulated to facilitate different neural computations is not known. Here, we investigated this issue in the insect olfactory system. We found that an odourant can generate synchronous or asynchronous spiking activity across a neural ensemble in the antennal lobe circuit depending on its relative novelty with respect to a preceding stimulus. Regardless of variations in temporal spiking patterns, the activated combinations of neurons robustly represented stimulus identity. Consistent with this interpretation, locusts reliably recognized both solitary and sequential introductions of trained odourants in a quantitative behavioural assay. However, predictable behavioural responses across locusts were observed only to novel stimuli that evoked synchronized spiking patterns across neural ensembles. Hence, our results indicate that the combinatorial ensemble response encodes for stimulus identity, whereas the temporal structure of the ensemble response selectively emphasizes novel stimuli. PMID:25912016

  4. Perceived exertion scales attest to both intensity and exercise duration.

    PubMed

    Garcin, M; Billat, V

    2001-12-01

    The present purpose was to study the relationships between perceived exertion (RPE, ETL) and exercise duration for all-out runs eliciting vVO2 max. 12 endurance-trained men performed three exhausting exercises on an indoor track. The first test was an incremental exercise to measure their maximal oxygen uptake (VO2 max), the velocity associated with VO2 max (vVO2 max), the velocity of the lacate concentration threshold (vLT) and the velocity delta 50 (vdelta50: the velocity halfway between vVO2 max and vLT). The second and third tests were a constant load all-out run at vVO2 max and vdelta50 to measure the time to exhaustion at these intensities (tlim vVO2 max and tlim vdelta50, respectively). vdelta50 corresponded to 90.1 +/- 2.5% vVO2 max; tlim vVO2 max and tlim vdelta50 were equal to 286 +/- 71 sec. and 547+/- 157 sec., respectively. For a same given relative time (%tlim), athletes perceived exercise as harder and felt that they could endure less for vVO2 max than vdelta50. When subjects began to perceive exercise as "hard" (RPE = 15), they had run for only 36.4 +/- 26.8%tlim at vVO2 max, whereas they had run for 46.1 +/- 15.7 %tlim at vdelta50. These results indicate that RPE and ETL scales were a combined subjective estimation of both intensity and exercise duration for all-out runs at 90 and 100% vVO2 max. Therefore, this scale could be used to assess duration as well as intensity of exercise for the practical application in sport. Moreover, it could be suggested that exercise duration can be prescribed as a function of perceived exertion for healthy normal people. Consequently, perceived exertion could be an important tool to individualize the prescription of a training program. PMID:11806583

  5. Parallel Midbrain Microcircuits Perform Independent Temporal Transformations

    PubMed Central

    Huguenard, John; Knudsen, Eric

    2014-01-01

    The capacity to select the most important information and suppress distracting information is crucial for survival. The midbrain contains a network critical for the selection of the strongest stimulus for gaze and attention. In avians, the optic tectum (OT; called the superior colliculus in mammals) and the GABAergic nucleus isthmi pars magnocellularis (Imc) cooperate in the selection process. In the chicken, OT layer 10, located in intermediate layers, responds to afferent input with gamma periodicity (25–75 Hz), measured at the level of individual neurons and the local field potential. In contrast, Imc neurons, which receive excitatory input from layer 10 neurons, respond with tonic, unusually high discharge rates (>150 spikes/s). In this study, we reveal the source of this high-rate inhibitory activity: layer 10 neurons that project to the Imc possess specialized biophysical properties that enable them to transform afferent drive into high firing rates (∼130 spikes/s), whereas neighboring layer 10 neurons, which project elsewhere, transform afferent drive into lower-frequency, periodic discharge patterns. Thus, the intermediate layers of the OT contain parallel, intercalated microcircuits that generate different temporal patterns of activity linked to the functions of their respective downstream targets. PMID:24920618

  6. Parallel midbrain microcircuits perform independent temporal transformations.

    PubMed

    Goddard, C Alex; Huguenard, John; Knudsen, Eric

    2014-06-11

    The capacity to select the most important information and suppress distracting information is crucial for survival. The midbrain contains a network critical for the selection of the strongest stimulus for gaze and attention. In avians, the optic tectum (OT; called the superior colliculus in mammals) and the GABAergic nucleus isthmi pars magnocellularis (Imc) cooperate in the selection process. In the chicken, OT layer 10, located in intermediate layers, responds to afferent input with gamma periodicity (25-75 Hz), measured at the level of individual neurons and the local field potential. In contrast, Imc neurons, which receive excitatory input from layer 10 neurons, respond with tonic, unusually high discharge rates (>150 spikes/s). In this study, we reveal the source of this high-rate inhibitory activity: layer 10 neurons that project to the Imc possess specialized biophysical properties that enable them to transform afferent drive into high firing rates (~130 spikes/s), whereas neighboring layer 10 neurons, which project elsewhere, transform afferent drive into lower-frequency, periodic discharge patterns. Thus, the intermediate layers of the OT contain parallel, intercalated microcircuits that generate different temporal patterns of activity linked to the functions of their respective downstream targets. PMID:24920618

  7. Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex

    PubMed Central

    Mohan, Hemanth; Verhoog, Matthijs B.; Doreswamy, Keerthi K.; Eyal, Guy; Aardse, Romy; Lodder, Brendan N.; Goriounova, Natalia A.; Asamoah, Boateng; B. Brakspear, A.B. Clementine; Groot, Colin; van der Sluis, Sophie; Testa-Silva, Guilherme; Obermayer, Joshua; Boudewijns, Zimbo S.R.M.; Narayanan, Rajeevan T.; Baayen, Johannes C.; Segev, Idan; Mansvelder, Huibert D.; de Kock, Christiaan P.J.

    2015-01-01

    The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on “full” human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of “full” human neuron morphologies and present direct evidence that human neurons are not “scaled-up” versions of rodent or macaque neurons, but have unique structural and functional properties. PMID:26318661

  8. Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration

    PubMed Central

    Stankiewicz, Trisha R.; Linseman, Daniel A.

    2014-01-01

    The Rho family of GTPases belongs to the Ras superfamily of low molecular weight (∼21 kDa) guanine nucleotide binding proteins. The most extensively studied members are RhoA, Rac1, and Cdc42. In the last few decades, studies have demonstrated that Rho family GTPases are important regulatory molecules that link surface receptors to the organization of the actin and microtubule cytoskeletons. Indeed, Rho GTPases mediate many diverse critical cellular processes, such as gene transcription, cell–cell adhesion, and cell cycle progression. However, Rho GTPases also play an essential role in regulating neuronal morphology. In particular, Rho GTPases regulate dendritic arborization, spine morphogenesis, growth cone development, and axon guidance. In addition, more recent efforts have underscored an important function for Rho GTPases in regulating neuronal survival and death. Interestingly, Rho GTPases can exert either a pro-survival or pro-death signal in neurons depending upon both the cell type and neurotoxic insult involved. This review summarizes key findings delineating the involvement of Rho GTPases and their effectors in the regulation of neuronal survival and death. Collectively, these results suggest that dysregulation of Rho family GTPases may potentially underscore the etiology of some forms of neurodegenerative disease such as amyotrophic lateral sclerosis. PMID:25339865

  9. Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration.

    PubMed

    Stankiewicz, Trisha R; Linseman, Daniel A

    2014-01-01

    The Rho family of GTPases belongs to the Ras superfamily of low molecular weight (∼21 kDa) guanine nucleotide binding proteins. The most extensively studied members are RhoA, Rac1, and Cdc42. In the last few decades, studies have demonstrated that Rho family GTPases are important regulatory molecules that link surface receptors to the organization of the actin and microtubule cytoskeletons. Indeed, Rho GTPases mediate many diverse critical cellular processes, such as gene transcription, cell-cell adhesion, and cell cycle progression. However, Rho GTPases also play an essential role in regulating neuronal morphology. In particular, Rho GTPases regulate dendritic arborization, spine morphogenesis, growth cone development, and axon guidance. In addition, more recent efforts have underscored an important function for Rho GTPases in regulating neuronal survival and death. Interestingly, Rho GTPases can exert either a pro-survival or pro-death signal in neurons depending upon both the cell type and neurotoxic insult involved. This review summarizes key findings delineating the involvement of Rho GTPases and their effectors in the regulation of neuronal survival and death. Collectively, these results suggest that dysregulation of Rho family GTPases may potentially underscore the etiology of some forms of neurodegenerative disease such as amyotrophic lateral sclerosis. PMID:25339865

  10. Quantum neuron design

    NASA Astrophysics Data System (ADS)

    Behrman, Elizabeth; Steck, James

    2014-03-01

    In previous work, we have developed quantum systems that can learn and do information processing much like artificial neural networks. These learning methods have some advantages over other implementations of quantum computing in that they construct their own algorithms and could be robust to noise and decoherence. Here we take the next step, by designing quantum neurons that have some of the important behaviors of biological neurons, yet have the advantage of being complex valued and having quantum computing power. Our neuron model consists of a two-level system coupled to a Gaussian bath representing the environment. Simulations of a interconnected network of these neurons show that the model can both learn standard AI tasks, as similar networks of classical neurons have been shown to do, and, in addition, perform quantum mechanical calculations.

  11. DCP-LA Exerts an Antiaging Action on the Skin.

    PubMed

    Nishizaki, Tomoyuki

    2016-01-01

    The present study assessed the possibility for the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) as an antiaging compound for the skin by assaying senescence-associated β-galactosidase (SA-β-Gal), a biomarker of senescence and cell viability. The nitric oxide (NO) donor sodium nitroprusside (SNP) increased in SA-β-Gal-positive cells in cultured human fibroblasts and mouse keratinocytes, and DCP-LA significantly inhibited the effect of SNP. Moreover, SNP induced cell death in cultured mouse keratinocytes, and DCP-LA significantly prevented NO stress-induced death of keratinocytes. Taken together, these results indicate that DCP-LA exerts an antiaging action on the skin. PMID:27310436

  12. Estimation of the exertion requirements of coal mining work

    SciTech Connect

    Harber, P.; Tamimie, J.; Emory, J.

    1984-02-01

    The work requirements of coal mining work were estimated by studying a group of 12 underground coal miners. A two level (rest, 300 kg X m/min) test was performed to estimate the linear relationship between each subject's heart rate and oxygen consumption. Then, heart rates were recorded during coal mining work with a Holter type recorder. From these data, the distributions of oxygen consumptions during work were estimated, allowing characterization of the range of exertion throughout the work day. The average median estimated oxygen consumption was 3.3 METS, the average 70th percentile was 4.3 METS, and the average 90th percentile was 6.3 METS. These results should be considered when assessing an individual's occupational fitness.

  13. Bmp Signaling Exerts Opposite Effects on Cardiac Differentiation

    PubMed Central

    de Pater, Emma; Ciampricotti, Metamia; Priller, Florian; Veerkamp, Justus; Strate, Ina; Smith, Kelly; Lagendijk, Anne Karine; Schilling, Thomas F.; Herzog, Wiebke; Abdelilah-Seyfried, Salim; Hammerschmidt, Matthias; Bakkers, Jeroen

    2016-01-01

    Rationale The importance for Bmp signaling during embryonic stem cell differentiation into myocardial cells has been recognized. The question when and where Bmp signaling in vivo regulates myocardial differentiation has remained largely unanswered. Objective To identify when and where Bmp signaling regulates cardiogenic differentiation. Methods and Results Here we have observed that in zebrafish embryos, Bmp signaling is active in cardiac progenitor cells prior to their differentiation into cardiomyocytes. Bmp signaling is continuously required during somitogenesis within the anterior lateral plate mesoderm to induce myocardial differentiation. Surprisingly, Bmp signaling is actively repressed in differentiating myocardial cells. We identified the inhibitory Smad6a, which is expressed in the cardiac tissue, to be required to inhibit Bmp signaling and thereby promote expansion of the ventricular myocardium. Conclusion Bmp signaling exerts opposing effects on myocardial differentiation in the embryo by promoting as well as inhibiting cardiac growth. PMID:22247485

  14. Nonoperative Management of Chronic Exertional Compartment Syndrome: A Systematic Review.

    PubMed

    Rajasekaran, Sathish; Hall, Mederic M

    2016-01-01

    Although nonoperative treatment options for chronic exertional compartment syndrome (CECS) are often used in clinical practice, supporting evidence is limited. The objective of this study was to systematically review the literature for nonsurgical treatment options for CECS of the lower leg. The literature search identified seven articles describing in total four different treatment options: massage, gait changes, chemodenervation, and ultrasound-guided (USG) fascial fenestration. Pertinent studies were in the form of case series and one case report, which limited the robustness of the data. Nevertheless, all four treatment options have little to no reported adverse effect profiles and can be considered in clinical practice. In addition, gait changes and USG fascial fenestration were found to have continued effect at 1 and 1.5 years, respectively. PMID:27172084

  15. Exertional heat stroke and acute liver failure: a late dysfunction.

    PubMed

    Carvalho, Ana Sofia; Rodeia, Simão C; Silvestre, Joana; Póvoa, Pedro

    2016-01-01

    Heat stroke (HS) is defined as a severe elevation of core body temperature along with central nervous system dysfunction. Exertional heat stroke (EHS) with acute liver failure (ALF) is a rare condition. The authors report the case of a 25-year-old man with a history of cognitive enhancers' intake who developed hyperthermia and neurological impairment while running an outdoor marathon. The patient was cooled and returned to normal body temperature after 6 h. He subsequently developed ALF and was transferred to the intensive care unit. Over-the-counter drug intake may have been related to heat intolerance and contributed to the event. The patient was successfully treated with conservative measures. In the presence of EHS, it is crucial to act promptly with aggressive total body cooling, in order to prevent progression of the clinical syndrome. Liver function must also be monitored, since it can be a late organ dysfunction. PMID:26969359

  16. Temporal Non-locality

    NASA Astrophysics Data System (ADS)

    Filk, Thomas

    2013-04-01

    In this article I investigate several possibilities to define the concept of "temporal non-locality" within the standard framework of quantum theory. In particular, I analyze the notions of "temporally non-local states", "temporally non-local events" and "temporally non-local observables". The idea of temporally non-local events is already inherent in the standard formalism of quantum mechanics, and Basil Hiley recently defined an operator in order to measure the degree of such a temporal non-locality. The concept of temporally non-local states enters as soon as "clock-representing states" are introduced in the context of special and general relativity. It is discussed in which way temporally non-local measurements may find an interesting application for experiments which test temporal versions of Bell inequalities.

  17. Traction Stresses Exerted by Adherent Cells: From Angiogenesis to Metastasis

    NASA Astrophysics Data System (ADS)

    Reinhart-King, Cynthia

    2010-03-01

    Cells exert traction stresses against their substrate that mediate their ability to sense the mechanical properties of their microenvironment. These same forces mediate cell adhesion, migration and the formation of stable cell-cell contacts during tissue formation. In this talk, I will present our data on the traction stresses generated by endothelial cells and metastatic breast cancer cells focused on understanding the processes of angiogenesis and metastasis, respectively. In the context of capillary formation, our data indicate that the mechanics of the substrate play a critical role in establishing endothelial cell-cell contacts. On more compliant substrates, endothelial cell shape and traction stresses polarize and promote the formation of stable cell-cell contacts. On stiffer substrates, traction stresses are less polarized and cell connectivity is disrupted. These data indicate that the mechanical properties of the microenvironment may drive cell connectivity and the formation of stable cell-cell contacts through the reorientation of traction stresses. In our studies of metastatic cell migration, we have found that traction stresses increase with increasing metastatic potential. We investigated three lines of varying metastatic potential (MCF10A, MCF7 and MDAMB231). MDAMB231, which are the most invasive, exert the most significant forces as measured by Traction Force Microscopy. These data present the possibility that cellular traction stress generation aids in the ability of metastatic cells to migrate through the matrix-dense tumor microenvironment. Such measurements are integral to link the mechanical and chemical microenvironment with the resulting response of the cell in health and disease.

  18. Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease

    PubMed Central

    Jason, Leonard A.; Sunnquist, Madison; Brown, Abigail; Newton, Julia L.; Strand, Elin Bolle; Vernon, Suzanne D.

    2015-01-01

    Background The Institute of Medicine has recommended a change in the name and criteria for Chronic Fatigue Syndrome (CFS), renaming the illness Systemic Exertion Intolerance Disease (SEID). The new SEID case definition requires substantial reductions or impairments in the ability to engage in pre-illness activities, unrefreshing sleep, post-exertional malaise, and either cognitive impairment or orthostatic intolerance. Purpose In the current study, samples were generated through several different methods and were used to compare this new case definition to previous case definitions for CFS, Myalgic Encephalomyelitis (ME-ICC), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), as well as a case definition developed through empirical methods. Methods We used a cross-sectional design with samples from tertiary care settings, a biobank sample, and other forums. 796 patients from the US, Great Britain, and Norway completed the DePaul Symptom Questionnaire. Results Findings indicated that the SEID criteria identified 88% of participants in the samples analyzed, which is comparable to the 92% that met the Fukuda criteria. The SEID case definition was compared to a four item empiric criteria, and findings indicated that the four item empiric criteria identified a smaller, more functionally limited and symptomatic group of patients. Conclusion The recently developed SEID criteria appears to identify a group comparable in size to the Fukuda et al. criteria, but a larger group of patients than the Canadian ME/CFS and ME criteria, and selects more patients who have less impairment and fewer symptoms than a four item empiric criteria. PMID:26345409

  19. Temporal structure coding with and without awareness.

    PubMed

    Faivre, N; Koch, C

    2014-06-01

    In order to interpret a constantly changing environment, visual events far apart in space and time must be integrated into a unified percept. While spatial properties of invisible signals are known to be encoded without awareness, the fate of temporal properties remains largely unknown. Here, we probed temporal integration for two distinct motion stimuli that were either visible or rendered invisible using continuous flash suppression. We found that when invisible, both the direction of apparent motion and the gender of point-light walkers were processed only when defined across short time periods (i.e., respectively 100 ms and 1000 ms). This limitation was not observed under full visibility. These similar findings at two different hierarchical levels of processing suggest that temporal integration windows shrink in the absence of perceptual awareness. We discuss this phenomenon as a key prediction of the global neuronal workspace and the information integration theories of consciousness. PMID:24681581

  20. Temporal Ventriloquism in a Purely Temporal Context

    ERIC Educational Resources Information Center

    Hartcher-O'Brien, Jessica; Alais, David

    2011-01-01

    This study examines how audiovisual signals are combined in time for a temporal analogue of the ventriloquist effect in a purely temporal context, that is, no spatial grounding of signals or other spatial facilitation. Observers were presented with two successive intervals, each defined by a 1250-ms tone, and indicated in which interval a brief…

  1. Physical Exertion and Immediate Classroom Mental Performance Among Elementary School Children.

    ERIC Educational Resources Information Center

    Gabbard, Carl

    This study was designed (1) to investigate the relationship between physical exertion and mental performance in elementary school children and (2) to determine if male or female mental performances are more affected by physical exertion. A total of 95 second graders participated in six treatments of induced physical exertion during their regularly…

  2. Insulin exerts neuroprotective effects via Akt/Bcl-2 signaling pathways in differentiated SH-SY5Y cells.

    PubMed

    Ramalingam, Mahesh; Kim, Sung-Jin

    2015-02-01

    In the present study, the changes in the cell viability at different concentrations of hydrogen peroxide (H2O2) for 3 h used to establish a model of oxidative stress. Further assays with 200 μM H2O2 induces significant changes in the levels of lactate dehydrogenase (LDH), nitric oxide (NO), reactive oxygen species (ROS) and calcium ion (Ca(2+)) in neuronal cells, but insulin can effectively diminish the oxidative damages. Moreover, cells treated with insulin increased the H2O2-induced suppression of glutathione levels and exerted an apparent suppressive effect on oxidative products. The results of Akt, Bcl-2, Bax, IRβ, IGF-1Rβ, IRS-1 and IRS-2 showed that insulin treatment had a protective effect on H2O2-induced oxidative stress in RA-differentiated SH-SY5Y neuroblastoma cells. PMID:24849496

  3. Neuron-astrocyte signaling and epilepsy.

    PubMed

    Seifert, Gerald; Steinhäuser, Christian

    2013-06-01

    Astrocytes express a plethora of ion channels, neurotransmitter receptors and transporters and thus are endowed with the machinery to sense and respond to neuronal activity. Recent studies have implicated astrocytes in important physiological roles in the CNS, such as synchronization of neuronal firing, ion homeostasis, neurotransmitter uptake, glucose metabolism and regulation of the vascular tone. Astrocytes are abundantly coupled through gap junctions allowing them to redistribute elevated K(+) concentration from sites of excessive neuronal activity. Growing evidence now suggests that dysfunctional astrocytes are crucial players in epilepsy. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization and function of astroglial K(+) and water channels, entailing impaired K(+) buffering. Moreover, malfunction of glutamate transporters and the astrocytic glutamate-converting enzyme, glutamine synthetase, as observed in epileptic tissue suggested that astrocyte dysfunction is causative of hyperexcitation, seizure spread and neurotoxicity. Accordingly, dysfunctional astrocytes should be considered as promising targets for new therapeutic strategies. In this review, we will summarize current knowledge of astrocyte dysfunction in temporal lobe epilepsy and discuss putative mechanisms underlying these alterations. PMID:21925173

  4. Estimating nonstationary input signals from a single neuronal spike train

    NASA Astrophysics Data System (ADS)

    Kim, Hideaki; Shinomoto, Shigeru

    2012-11-01

    Neurons temporally integrate input signals, translating them into timed output spikes. Because neurons nonperiodically emit spikes, examining spike timing can reveal information about input signals, which are determined by activities in the populations of excitatory and inhibitory presynaptic neurons. Although a number of mathematical methods have been developed to estimate such input parameters as the mean and fluctuation of the input current, these techniques are based on the unrealistic assumption that presynaptic activity is constant over time. Here, we propose tracking temporal variations in input parameters with a two-step analysis method. First, nonstationary firing characteristics comprising the firing rate and non-Poisson irregularity are estimated from a spike train using a computationally feasible state-space algorithm. Then, information about the firing characteristics is converted into likely input parameters over time using a transformation formula, which was constructed by inverting the neuronal forward transformation of the input current to output spikes. By analyzing spike trains recorded in vivo, we found that neuronal input parameters are similar in the primary visual cortex V1 and middle temporal area, whereas parameters in the lateral geniculate nucleus of the thalamus were markedly different.

  5. Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression.

    PubMed

    Courtin, Julien; Chaudun, Fabrice; Rozeske, Robert R; Karalis, Nikolaos; Gonzalez-Campo, Cecilia; Wurtz, Hélène; Abdi, Azzedine; Baufreton, Jerome; Bienvenu, Thomas C M; Herry, Cyril

    2014-01-01

    Synchronization of spiking activity in neuronal networks is a fundamental process that enables the precise transmission of information to drive behavioural responses. In cortical areas, synchronization of principal-neuron spiking activity is an effective mechanism for information coding that is regulated by GABA (γ-aminobutyric acid)-ergic interneurons through the generation of neuronal oscillations. Although neuronal synchrony has been demonstrated to be crucial for sensory, motor and cognitive processing, it has not been investigated at the level of defined circuits involved in the control of emotional behaviour. Converging evidence indicates that fear behaviour is regulated by the dorsomedial prefrontal cortex (dmPFC). This control over fear behaviour relies on the activation of specific prefrontal projections to the basolateral complex of the amygdala (BLA), a structure that encodes associative fear memories. However, it remains to be established how the precise temporal control of fear behaviour is achieved at the level of prefrontal circuits. Here we use single-unit recordings and optogenetic manipulations in behaving mice to show that fear expression is causally related to the phasic inhibition of prefrontal parvalbumin interneurons (PVINs). Inhibition of PVIN activity disinhibits prefrontal projection neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. Our results identify two complementary neuronal mechanisms mediated by PVINs that precisely coordinate and enhance the neuronal activity of prefrontal projection neurons to drive fear expression. PMID:24256726

  6. Spike sorting of synchronous spikes from local neuron ensembles.

    PubMed

    Franke, Felix; Pröpper, Robert; Alle, Henrik; Meier, Philipp; Geiger, Jörg R P; Obermayer, Klaus; Munk, Matthias H J

    2015-10-01

    Synchronous spike discharge of cortical neurons is thought to be a fingerprint of neuronal cooperativity. Because neighboring neurons are more densely connected to one another than neurons that are located further apart, near-synchronous spike discharge can be expected to be prevalent and it might provide an important basis for cortical computations. Using microelectrodes to record local groups of neurons does not allow for the reliable separation of synchronous spikes from different cells, because available spike sorting algorithms cannot correctly resolve the temporally overlapping waveforms. We show that high spike sorting performance of in vivo recordings, including overlapping spikes, can be achieved with a recently developed filter-based template matching procedure. Using tetrodes with a three-dimensional structure, we demonstrate with simulated data and ground truth in vitro data, obtained by dual intracellular recording of two neurons located next to a tetrode, that the spike sorting of synchronous spikes can be as successful as the spike sorting of nonoverlapping spikes and that the spatial information provided by multielectrodes greatly reduces the error rates. We apply the method to tetrode recordings from the prefrontal cortex of behaving primates, and we show that overlapping spikes can be identified and assigned to individual neurons to study synchronous activity in local groups of neurons. PMID:26289473

  7. Dysarthria of Motor Neuron Disease: Clinician Judgments of Severity.

    ERIC Educational Resources Information Center

    Seikel, J. Anthony; And Others

    1990-01-01

    This study investigated the relationship between the temporal-acoustic parameters of the speech of 15 adults with motor neuron disease. Differences in predictions of the progression of the disease and clinician judgments of dysarthria severity were found to relate to the linguistic systems of both speaker and judge. (Author/JDD)

  8. The Representation of Information about Faces in the Temporal and Frontal Lobes

    ERIC Educational Resources Information Center

    Rolls, Edmund T.

    2007-01-01

    Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size and view of faces and objects, and that these neurons show rapid processing and rapid learning. Which face or object is present is encoded using a distributed…

  9. Diverse precerebellar neurons share similar intrinsic excitability.

    PubMed

    Kolkman, Kristine E; McElvain, Lauren E; du Lac, Sascha

    2011-11-16

    The cerebellum dedicates a majority of the brain's neurons to processing a wide range of sensory, motor, and cognitive signals. Stereotyped circuitry within the cerebellar cortex suggests that similar computations are performed throughout the cerebellum, but little is known about whether diverse precerebellar neurons are specialized for the nature of the information they convey. In vivo recordings indicate that firing responses to sensory or motor stimuli vary dramatically across different precerebellar nuclei, but whether this reflects diverse synaptic inputs or differentially tuned intrinsic excitability has not been determined. We targeted whole-cell patch-clamp recordings to neurons in eight precerebellar nuclei which were retrogradely labeled from different regions of the cerebellum in mice. Intrinsic physiology was compared across neurons in the medial vestibular, external cuneate, lateral reticular, prepositus hypoglossi, supragenual, Roller/intercalatus, reticularis tegmenti pontis, and pontine nuclei. Within the firing domain, precerebellar neurons were remarkably similar. Firing faithfully followed temporally modulated inputs, could be sustained at high rates, and was a linear function of input current over a wide range of inputs and firing rates. Pharmacological analyses revealed common expression of Kv3 currents, which were essential for a wide linear firing range, and of SK (small-conductance calcium-activated potassium) currents, which were essential for a wide linear input range. In contrast, membrane properties below spike threshold varied considerably within and across precerebellar nuclei, as evidenced by variability in postinhibitory rebound firing. Our findings indicate that diverse precerebellar neurons perform similar scaling computations on their inputs but may be differentially tuned to synaptic inhibition. PMID:22090493

  10. Transporting mitochondria in neurons

    PubMed Central

    Course, Meredith M.; Wang, Xinnan

    2016-01-01

    Neurons demand vast and vacillating supplies of energy. As the key contributors of this energy, as well as primary pools of calcium and signaling molecules, mitochondria must be where the neuron needs them, when the neuron needs them. The unique architecture and length of neurons, however, make them a complex system for mitochondria to navigate. To add to this difficulty, mitochondria are synthesized mainly in the soma, but must be transported as far as the distant terminals of the neuron. Similarly, damaged mitochondria—which can cause oxidative stress to the neuron—must fuse with healthy mitochondria to repair the damage, return all the way back to the soma for disposal, or be eliminated at the terminals. Increasing evidence suggests that the improper distribution of mitochondria in neurons can lead to neurodegenerative and neuropsychiatric disorders. Here, we will discuss the machinery and regulatory systems used to properly distribute mitochondria in neurons, and how this knowledge has been leveraged to better understand neurological dysfunction. PMID:27508065

  11. How microglia kill neurons.

    PubMed

    Brown, Guy C; Vilalta, Anna

    2015-12-01

    Microglia are resident brain macrophages that become inflammatory activated in most brain pathologies. Microglia normally protect neurons, but may accidentally kill neurons when attempting to limit infections or damage, and this may be more common with degenerative disease as there was no significant selection pressure on the aged brain in the past. A number of mechanisms by which activated microglia kill neurons have been identified, including: (i) stimulation of the phagocyte NADPH oxidase (PHOX) to produce superoxide and derivative oxidants, (ii) expression of inducible nitric oxide synthase (iNOS) producing NO and derivative oxidants, (iii) release of glutamate and glutaminase, (iv) release of TNFα, (v) release of cathepsin B, (vi) phagocytosis of stressed neurons, and (vii) decreased release of nutritive BDNF and IGF-1. PHOX stimulation contributes to microglial activation, but is not directly neurotoxic unless NO is present. NO is normally neuroprotective, but can react with superoxide to produce neurotoxic peroxynitrite, or in the presence of hypoxia inhibit mitochondrial respiration. Glutamate can be released by glia or neurons, but is neurotoxic only if the neurons are depolarised, for example as a result of mitochondrial inhibition. TNFα is normally neuroprotective, but can become toxic if caspase-8 or NF-κB activation are inhibited. If the above mechanisms do not kill neurons, they may still stress the neurons sufficiently to make them susceptible to phagocytosis by activated microglia. We review here whether microglial killing of neurons is an artefact, makes evolutionary sense or contributes in common neuropathologies and by what mechanisms. This article is part of a Special Issue entitled SI: Neuroprotection. PMID:26341532

  12. Emergence of Slow-Switching Assemblies in Structured Neuronal Networks

    PubMed Central

    Schaub, Michael T.; Billeh, Yazan N.; Anastassiou, Costas A.; Koch, Christof; Barahona, Mauricio

    2015-01-01

    Unraveling the interplay between connectivity and spatio-temporal dynamics in neuronal networks is a key step to advance our understanding of neuronal information processing. Here we investigate how particular features of network connectivity underpin the propensity of neural networks to generate slow-switching assembly (SSA) dynamics, i.e., sustained epochs of increased firing within assemblies of neurons which transition slowly between different assemblies throughout the network. We show that the emergence of SSA activity is linked to spectral properties of the asymmetric synaptic weight matrix. In particular, the leading eigenvalues that dictate the slow dynamics exhibit a gap with respect to the bulk of the spectrum, and the associated Schur vectors exhibit a measure of block-localization on groups of neurons, thus resulting in coherent dynamical activity on those groups. Through simple rate models, we gain analytical understanding of the origin and importance of the spectral gap, and use these insights to develop new network topologies with alternative connectivity paradigms which also display SSA activity. Specifically, SSA dynamics involving excitatory and inhibitory neurons can be achieved by modifying the connectivity patterns between both types of neurons. We also show that SSA activity can occur at multiple timescales reflecting a hierarchy in the connectivity, and demonstrate the emergence of SSA in small-world like networks. Our work provides a step towards understanding how network structure (uncovered through advancements in neuroanatomy and connectomics) can impact on spatio-temporal neural activity and constrain the resulting dynamics. PMID:26176664

  13. Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington's disease.

    PubMed

    Johri, Ashu; Calingasan, Noel Y; Hennessey, Thomas M; Sharma, Abhijeet; Yang, Lichuan; Wille, Elizabeth; Chandra, Abhishek; Beal, M Flint

    2012-03-01

    There is substantial evidence that impairment of peroxisome proliferator-activated receptor (PPAR)-γ-coactivator 1α (PGC-1α) levels and activity play an important role in Huntington's disease (HD) pathogenesis. We tested whether pharmacologic treatment with the pan-PPAR agonist bezafibrate would correct a deficiency of PGC-1α and exert beneficial effects in a transgenic mouse model of HD. We found that administration of bezafibrate in the diet restored levels of PGC-1α, PPARs and downstream genes to levels which occur in wild-type mice. There were significant improvements in phenotype and survival. In the striatum, astrogliosis and neuronal atrophy were attenuated and numbers of mitochondria were increased. Bezafibrate treatment prevented conversion of type I oxidative to type II glycolytic muscle fibers and increased the numbers of muscle mitochondria. Finally, bezafibrate rescued lipid accumulation and apparent vacuolization of brown adipose tissue in the HD mice. These findings provide strong evidence that treatment with bezafibrate exerts neuroprotective effects which may be beneficial in the treatment of HD. PMID:22095692

  14. Leptin counteracts the hypoxia-induced inhibition of spontaneously firing hippocampal neurons: a microelectrode array study.

    PubMed

    Gavello, Daniela; Rojo-Ruiz, Jonathan; Marcantoni, Andrea; Franchino, Claudio; Carbone, Emilio; Carabelli, Valentina

    2012-01-01

    Besides regulating energy balance and reducing body-weight, the adipokine leptin has been recently shown to be neuroprotective and antiapoptotic by promoting neuronal survival after excitotoxic and oxidative insults. Here, we investigated the firing properties of mouse hippocampal neurons and the effects of leptin pretreatment on hypoxic damage (2 hours, 3% O(2)). Experiments were carried out by means of the microelectrode array (MEA) technology, monitoring hippocampal neurons activity from 11 to 18 days in vitro (DIV). Under normoxic conditions, hippocampal neurons were spontaneously firing, either with prevailing isolated and randomly distributed spikes (11 DIV), or with patterns characterized by synchronized bursts (18 DIV). Exposure to hypoxia severely impaired the spontaneous activity of hippocampal neurons, reducing their firing frequency by 54% and 69%, at 11 and 18 DIV respectively, and synchronized their firing activity. Pretreatment with 50 nM leptin reduced the firing frequency of normoxic neurons and contrasted the hypoxia-induced depressive action, either by limiting the firing frequency reduction (at both ages) or by increasing it to 126% (in younger neurons). In order to find out whether leptin exerts its effect by activating large conductance Ca(2+)-activated K(+) channels (BK), as shown on rat hippocampal neurons, we applied the BK channel blocker paxilline (1 µM). Our data show that paxilline reversed the effects of leptin, both on normoxic and hypoxic neurons, suggesting that the adipokine counteracts hypoxia through BK channels activation in mouse hippocampal neurons. PMID:22848520

  15. Leptin Counteracts the Hypoxia-Induced Inhibition of Spontaneously Firing Hippocampal Neurons: A Microelectrode Array Study

    PubMed Central

    Gavello, Daniela; Rojo-Ruiz, Jonathan; Marcantoni, Andrea; Franchino, Claudio; Carbone, Emilio; Carabelli, Valentina

    2012-01-01

    Besides regulating energy balance and reducing body-weight, the adipokine leptin has been recently shown to be neuroprotective and antiapoptotic by promoting neuronal survival after excitotoxic and oxidative insults. Here, we investigated the firing properties of mouse hippocampal neurons and the effects of leptin pretreatment on hypoxic damage (2 hours, 3% O2). Experiments were carried out by means of the microelectrode array (MEA) technology, monitoring hippocampal neurons activity from 11 to 18 days in vitro (DIV). Under normoxic conditions, hippocampal neurons were spontaneously firing, either with prevailing isolated and randomly distributed spikes (11 DIV), or with patterns characterized by synchronized bursts (18 DIV). Exposure to hypoxia severely impaired the spontaneous activity of hippocampal neurons, reducing their firing frequency by 54% and 69%, at 11 and 18 DIV respectively, and synchronized their firing activity. Pretreatment with 50 nM leptin reduced the firing frequency of normoxic neurons and contrasted the hypoxia-induced depressive action, either by limiting the firing frequency reduction (at both ages) or by increasing it to 126% (in younger neurons). In order to find out whether leptin exerts its effect by activating large conductance Ca2+-activated K+ channels (BK), as shown on rat hippocampal neurons, we applied the BK channel blocker paxilline (1 µM). Our data show that paxilline reversed the effects of leptin, both on normoxic and hypoxic neurons, suggesting that the adipokine counteracts hypoxia through BK channels activation in mouse hippocampal neurons. PMID:22848520

  16. Neuronal Functions of ESCRTs

    PubMed Central

    Gao, Fen-Biao

    2012-01-01

    The endosomal sorting complexes required for transport (ESCRTs) regulate protein trafficking from endosomes to lysosomes. Recent studies have shown that ESCRTs are involved in various cellular processes, including membrane scission, microRNA function, viral budding, and the autophagy pathway in many tissues, including the nervous system. Indeed, dysfunctional ESCRTs are associated with neurodegeneration. However, it remains largely elusive how ESCRTs act in post-mitotic neurons, a highly specialized cell type that requires dynamic changes in neuronal structures and signaling for proper function. This review focuses on our current understandings of the functions of ESCRTs in neuronal morphology, synaptic plasticity, and neurodegenerative diseases. PMID:22438674

  17. Multiscale fingerprinting of neuronal functional connectivity.

    PubMed

    Song, Gang; Tin, Chung; Poon, Chi-Sang

    2015-09-01

    Current cellular-based connectomics approaches aim to delineate the functional or structural organizations of mammalian brain circuits through neuronal activity mapping and/or axonal tracing. To discern possible connectivity between functionally identified neurons in widely distributed brain circuits, reliable and efficient network-based approaches of cross-registering or cross-correlating such functional-structural data are essential. Here, a novel cross-correlation approach that exploits multiple timing-specific, response-specific, and cell-specific neuronal characteristics as coincident fingerprint markers at the systems, network, and cellular levels is proposed. Application of this multiscale temporal-cellular coincident fingerprinting assay to the respiratory central pattern generator network in rats revealed a descending excitatory pathway with characteristic activity pattern and projecting from a distinct neuronal population in pons to its counterparts in medulla that control the post-inspiratory phase of the respiratory rhythm important for normal breathing, airway protection, and respiratory-vocalization coordination. This enabling neurotracing approach may prove valuable for functional connectivity mapping of other brain circuits. PMID:25056933

  18. Visualizing the spinal neuronal dynamics of locomotion

    NASA Astrophysics Data System (ADS)

    Subramanian, Kalpathi R.; Bashor, D. P.; Miller, M. T.; Foster, J. A.

    2004-06-01

    Modern imaging and simulation techniques have enhanced system-level understanding of neural function. In this article, we present an application of interactive visualization to understanding neuronal dynamics causing locomotion of a single hip joint, based on pattern generator output of the spinal cord. Our earlier work visualized cell-level responses of multiple neuronal populations. However, the spatial relationships were abstract, making communication with colleagues difficult. We propose two approaches to overcome this: (1) building a 3D anatomical model of the spinal cord with neurons distributed inside, animated by the simulation and (2) adding limb movements predicted by neuronal activity. The new system was tested using a cat walking central pattern generator driving a pair of opposed spinal motoneuron pools. Output of opposing motoneuron pools was combined into a single metric, called "Net Neural Drive", which generated angular limb movement in proportion to its magnitude. Net neural drive constitutes a new description of limb movement control. The combination of spatial and temporal information in the visualizations elegantly conveys the neural activity of the output elements (motoneurons), as well as the resulting movement. The new system encompasses five biological levels of organization from ion channels to observed behavior. The system is easily scalable, and provides an efficient interactive platform for rapid hypothesis testing.

  19. Asynchronous Rate Chaos in Spiking Neuronal Circuits.

    PubMed

    Harish, Omri; Hansel, David

    2015-07-01

    The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI) spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results. PMID:26230679

  20. Lower motor neuron dysfunction in ALS.

    PubMed

    de Carvalho, Mamede; Swash, Michael

    2016-07-01

    In the motor system there is a complex interplay between cortical structures and spinal cord lower motor neurons (LMN). In this system both inhibitory and excitatory neurons have relevant roles. LMN loss is a marker of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Conventional needle electromyography (EMG) does not allow LMN loss to be quantified. Measurement of compound muscle action potential (CMAP) amplitude or area, and the neurophysiological index, provide a surrogate estimate of the number of functional motor units. Increased motor neuronal excitability is a neurophysiological marker of ALS in the context of a suspected clinical and electrophysiological diagnosis. In the LMN system, fasciculation potentials (FPs) are the earliest changes observed in affected muscles, a feature of LMN hyperexcitability. Reinnervation is best investigated by needle EMG although other methods can be explored. Moreover needle EMG give information about the temporal profile of the reinnervation process, important ancillary data. Quantitative motor unit potential analysis is a valuable method of evaluating reinnervation. The importance of FPs has been recognized in the Awaji criteria for the electrodiagnosis of ALS, criteria that are a sensitive adjunct to the revised El Escorial criteria. Finally, functionality of LMN's, and perhaps excitability studies in motor nerves, aids understanding of the disease process, allowing measurement of potential treatment effects in clinical trials. Other investigational techniques, such as electrical impedance myography, muscle and nerve ultrasound, and spinal cord imaging methods may prove useful in future. PMID:27117334

  1. A model of the temporal dynamics of multisensory enhancement

    PubMed Central

    Rowland, Benjamin A.; Stein, Barry E.

    2014-01-01

    The senses transduce different forms of environmental energy, and the brain synthesizes information across them to enhance responses to salient biological events. We hypothesize that the potency of multisensory integration is attributable to the convergence of independent and temporally aligned signals derived from cross-modal stimulus configurations onto multisensory neurons. The temporal profile of multisensory integration in neurons of the deep superior colliculus (SC) is consistent with this hypothesis. The responses of these neurons to visual, auditory, and combinations of visual–auditory stimuli reveal that multisensory integration takes place in real-time; that is, the input signals are integrated as soon as they arrive at the target neuron. Interactions between cross-modal signals may appear to reflect linear or nonlinear computations on a moment-by-moment basis, the aggregate of which determines the net product of multisensory integration. Modeling observations presented here suggest that the early nonlinear components of the temporal profile of multisensory integration can be explained with a simple spiking neuron model, and do not require more sophisticated assumptions about the underlying biology. A transition from nonlinear “super-additive” computation to linear, additive computation can be accomplished via scaled inhibition. The findings provide a set of design constraints for artificial implementations seeking to exploit the basic principles and potency of biological multisensory integration in contexts of sensory substitution or augmentation. PMID:24374382

  2. Temporal-Spatial Correlation between Angiogenesis and Corticogenesis in the Developing Chick Optic Tectum

    PubMed Central

    Celin, Alejandra Rodriguez; Rapacioli, Melina; Gonzalez, Mariela Azul; Ballarin, Virginia Laura; de Plazas, Sara Fiszer; López-Costa, Juan José; Flores, Vladimir

    2015-01-01

    The developing chick optic tectum is a widely used model of corticogenesis and angiogenesis. Cell behaviors involved in corticogenesis and angiogenesis share several regulatory mechanisms. In this way the 3D organizations of both systems adapt to each other. The consensus about the temporally and spatially organized progression of the optic tectum corticogenesis contrasts with the discrepancies about the spatial organization of its vascular bed as a function of the time. In order to find out spatial and temporal correlations between corticogenesis and angiogenesis, several methodological approaches were applied to analyze the dynamic of angiogenesis in the developing chick optic tectum. The present paper shows that a typical sequence of developmental events characterizes the optic tectum angiogenesis. The first phase, formation of the primitive vascular bed, takes place during the early stages of the tectal corticogenesis along which the large efferent neurons appear and begin their early differentiation. The second phase, remodeling and elaboration of the definitive vascular bed, occurs during the increase in complexity associated to the elaboration of the local circuit networks. The present results show that, apart from the well-known influence of the dorsal-ventral and radial axes as reference systems for the spatial organization of optic tectum angiogenesis, the cephalic-caudal axis also exerts a significant asymmetric influence. The term cortico-angiogenesis to describe the entire process is justified by the fact that tight correlations are found between specific corticogenic and angiogenic events and they take place simultaneously at the same position along the cephalic-caudal and radial axes. PMID:25633659

  3. Temporal-spatial correlation between angiogenesis and corticogenesis in the developing chick optic tectum.

    PubMed

    Rodriguez Celin, Alejandra; Rapacioli, Melina; Gonzalez, Mariela Azul; Ballarin, Virginia Laura; Fiszer de Plazas, Sara; López-Costa, Juan José; Flores, Vladimir

    2015-01-01

    The developing chick optic tectum is a widely used model of corticogenesis and angiogenesis. Cell behaviors involved in corticogenesis and angiogenesis share several regulatory mechanisms. In this way the 3D organizations of both systems adapt to each other. The consensus about the temporally and spatially organized progression of the optic tectum corticogenesis contrasts with the discrepancies about the spatial organization of its vascular bed as a function of the time. In order to find out spatial and temporal correlations between corticogenesis and angiogenesis, several methodological approaches were applied to analyze the dynamic of angiogenesis in the developing chick optic tectum. The present paper shows that a typical sequence of developmental events characterizes the optic tectum angiogenesis. The first phase, formation of the primitive vascular bed, takes place during the early stages of the tectal corticogenesis along which the large efferent neurons appear and begin their early differentiation. The second phase, remodeling and elaboration of the definitive vascular bed, occurs during the increase in complexity associated to the elaboration of the local circuit networks. The present results show that, apart from the well-known influence of the dorsal-ventral and radial axes as reference systems for the spatial organization of optic tectum angiogenesis, the cephalic-caudal axis also exerts a significant asymmetric influence. The term cortico-angiogenesis to describe the entire process is justified by the fact that tight correlations are found between specific corticogenic and angiogenic events and they take place simultaneously at the same position along the cephalic-caudal and radial axes. PMID:25633659

  4. Model reduction of strong-weak neurons.

    PubMed

    Du, Bosen; Sorensen, Danny; Cox, Steven J

    2014-01-01

    We consider neurons with large dendritic trees that are weakly excitable in the sense that back propagating action potentials are severly attenuated as they travel from the small, strongly excitable, spike initiation zone. In previous work we have shown that the computational size of weakly excitable cell models may be reduced by two or more orders of magnitude, and that the size of strongly excitable models may be reduced by at least one order of magnitude, without sacrificing the spatio-temporal nature of its inputs (in the sense we reproduce the cell's precise mapping of inputs to outputs). We combine the best of these two strategies via a predictor-corrector decomposition scheme and achieve a drastically reduced highly accurate model of a caricature of the neuron responsible for collision detection in the locust. PMID:25566048

  5. Model reduction of strong-weak neurons

    PubMed Central

    Du, Bosen; Sorensen, Danny; Cox, Steven J.

    2014-01-01

    We consider neurons with large dendritic trees that are weakly excitable in the sense that back propagating action potentials are severly attenuated as they travel from the small, strongly excitable, spike initiation zone. In previous work we have shown that the computational size of weakly excitable cell models may be reduced by two or more orders of magnitude, and that the size of strongly excitable models may be reduced by at least one order of magnitude, without sacrificing the spatio–temporal nature of its inputs (in the sense we reproduce the cell's precise mapping of inputs to outputs). We combine the best of these two strategies via a predictor-corrector decomposition scheme and achieve a drastically reduced highly accurate model of a caricature of the neuron responsible for collision detection in the locust. PMID:25566048

  6. Neuromorphic silicon neuron circuits.

    PubMed

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin-Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  7. Neuronal ubiquitin homeostasis

    PubMed Central

    Hallengren, Jada; Chen, Ping-Chung; Wilson, Scott M.

    2013-01-01

    Neurons have highly specialized intracellular compartments that facilitate the development and activity of the nervous system. Ubiquitination is a post-translational modification that controls many aspects of neuronal function by regulating protein abundance. Disruption of this signaling pathway has been demonstrated in neurological disorders such as Parkinson’s disease, Amyotrophic Lateral Sclerosis and Angleman Syndrome. Since many neurological disorders exhibit ubiquitinated protein aggregates, the loss of neuronal ubiquitin homeostasis may be an important contributor of disease. This review discusses the mechanisms utilized by neurons to control the free pool of ubiquitin necessary for normal nervous system development and function as well as new roles of protein ubiquitination in regulating synaptic activity. PMID:23686613

  8. Neuromorphic Silicon Neuron Circuits

    PubMed Central

    Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

    2011-01-01

    Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

  9. Medial temporal N-acetyl aspartate in pediatric major depression

    PubMed Central

    MacMaster, Frank P.; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S. Preeya; Buhagiar, Christian; Rosenberg, David R.

    2008-01-01

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD-case control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  10. Medial temporal N-acetyl-aspartate in pediatric major depression.

    PubMed

    MacMaster, Frank P; Moore, Gregory J; Russell, Aileen; Mirza, Yousha; Taormina, S Preeya; Buhagiar, Christian; Rosenberg, David R

    2008-10-30

    The medial temporal cortex (MTC) has been implicated in the pathogenesis of pediatric major depressive disorder (MDD). Eleven MDD case-control pairs underwent proton magnetic resonance spectroscopic imaging. N-acetyl-aspartate was lower in the left MTC (27%) in MDD patients versus controls. Lower N-acetyl-aspartate concentrations in MDD patients may reflect reduced neuronal viability. PMID:18703320

  11. The Rhythm Aftereffect: Support for Time Sensitive Neurons with Broad Overlapping Tuning Curves

    ERIC Educational Resources Information Center

    Becker, Mark W.; Rasmussen, Ian P.

    2007-01-01

    Ivry [Ivry, R. B. (1996). The representation of temporal information in perception and motor control. Current Opinion in Neurobiology, 6, 851-857.] proposed that explicit coding of brief time intervals is accomplished by neurons that are tuned to a preferred temporal interval and have broad overlapping tuning curves. This proposal is analogous to…

  12. Formwork pressure exerted by self-consolidating concrete

    NASA Astrophysics Data System (ADS)

    Omran, Ahmed Fathy

    Self-consolidating concrete (SCC) is an emerging technology that utilizes flowable concrete that eliminates the need for consolidation. The advantages of SCC lie in a remarkable reduction of the casting time, facilitating the casting of congested and complex structural elements, possibility to reduce labor demand, elimination of mechanical vibrations and noise, improvement of surface appearance, producing a better and premium concrete product. The research focussed on capturing existing knowledge and making recommendations for current practice. An experimental program was undertaken at the Universite de Sherbrooke to evaluate the lateral pressure developed by SCC mixtures. A portable devise (UofS2 pressure column) for measuring and predicting lateral pressure and its rate of decay of SCC was developed and validated. The UofS2 pressure column is cast with 0.5 m high fresh concrete and air pressure is introduced from the top to simulate casting depth up to 13 m. Then, develop and implement test method for field evaluation of relevant plastic and thixotropic properties of SCC that affect formwork pressure were done. Portable vane (PV) test based on the hand-held vane test method used to determine the undrained shear strength property of clay soil was the first setup as well as the inclined plane (IP) test. The IP device involves slumping a small concrete cylinder on a horizontal plate and then lifting up the plate at different durations of rest until the slumped sample starts to move. Identifying role of material constituents, mix design, concrete placement characteristics (casting rate, waiting periods between lifts, and casting depth), temperature, and formwork characteristics that have major influence on formwork pressure exerted by SCC were evaluated in laboratory and validated by actual field measurements. Relating the maximum lateral pressure and its rate of decay to the plastic properties of SCC were established. In the analytical part of the research

  13. Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension.

    PubMed

    Laveneziana, Pierantonio; Garcia, Gilles; Joureau, Barbara; Nicolas-Jilwan, Fadia; Brahimi, Toufik; Laviolette, Louis; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc; Similowski, Thomas

    2013-03-01

    Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea. PMID:22790921

  14. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

    PubMed Central

    Oláh, Attila; Tóth, Balázs I.; Borbíró, István; Sugawara, Koji; Szöllõsi, Attila G.; Czifra, Gabriella; Pál, Balázs; Ambrus, Lídia; Kloepper, Jennifer; Camera, Emanuela; Ludovici, Matteo; Picardo, Mauro; Voets, Thomas; Zouboulis, Christos C.; Paus, Ralf; Bíró, Tamás

    2014-01-01

    The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris. PMID:25061872

  15. The biomolecule ubiquinone exerts a variety of biological functions.

    PubMed

    Nohl, Hans; Staniek, Katrin; Kozlov, Andrey V; Gille, Lars

    2003-01-01

    The chemistry of ubiquinone allows reversible addition of single electrons and protons. This unique property is used in nature for aerobic energy gain, for unilateral proton accumulation, for the generation of reactive oxygen species involved in physiological signaling and a variety of pathophysiological events. Since several years ubiquinone is also considered to play a major role in the control of lipid peroxidation, since this lipophilic biomolecule was recognized to recycle alpha-tocopherol radicals back to the chain-breaking form, vitamin E. Ubiquinone is therefore a biomolecule which has increasingly focused the interest of many research groups due to its alternative pro- and antioxidant activity. We have intensively investigated the role of ubiquinone as prooxidant in mitochondria and will present experimental evidences on conditions required for this function, we will also show that lysosomal ubiquinone has a double function as proton translocator and radical source under certain metabolic conditions. Furthermore, we have addressed the antioxidant role of ubiquinone and found that the efficiency of this activity is widely dependent on the type of biomembrane where ubiquinone exerts its chain-breaking activity. PMID:14695917

  16. Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo.

    PubMed

    Nussbaumer, Markus; Asara, John M; Teplytska, Larysa; Murphy, Michael P; Logan, Angela; Turck, Christoph W; Filiou, Michaela D

    2016-06-01

    Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no reported side effects in mice and humans. PMID:26567514

  17. Return to activity following fasciotomy for chronic exertional compartment syndrome.

    PubMed

    Irion, Val; Magnussen, Robert A; Miller, Timothy L; Kaeding, Christopher C

    2014-10-01

    Diagnosis of chronic exertional compartment syndrome (CECS) is relatively rare but has been well documented in athletes. There are, however, few reports regarding return to athletic activity after surgery among elite-level athletes. We hypothesized that a majority of elite-level athletes would successfully return to their previous level of competition following fasciotomy for CECS. A retrospective chart review was performed to identify elite-level athletes (collegiate or professional sport participation) who underwent fasciotomy for CECS over a 3-year period. Data collected included sport or activity, treatment and surgical details, time away from sport/activity after surgery, and ability to return to prior level of activity. Six males and seven females were included in the analysis. Patient age ranged from 17 to 24 years with a mean of 19.7 years. Six patients underwent unilateral lower extremity compartment release, and seven underwent bilateral lower extremity compartment release. The anterior and lateral compartments alone were released in 11 patients (84.6%). Two patients (15.4%) underwent four-compartment releases. Eleven patients (84.6%) were able to return to their previous elite level of sport participation at a mean of 10.6 weeks following surgical fasciotomy. Patients who had four-compartment release had a more than 3.5 week average longer return to full sporting activities (p = 0.011). Fasciotomy is effective in allowing elite athletes with CECS to return to sport. PMID:24664450

  18. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes.

    PubMed

    Oláh, Attila; Tóth, Balázs I; Borbíró, István; Sugawara, Koji; Szöllõsi, Attila G; Czifra, Gabriella; Pál, Balázs; Ambrus, Lídia; Kloepper, Jennifer; Camera, Emanuela; Ludovici, Matteo; Picardo, Mauro; Voets, Thomas; Zouboulis, Christos C; Paus, Ralf; Bíró, Tamás

    2014-09-01

    The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris. PMID:25061872

  19. Effects of caffeine on the rate of perceived exertion.

    PubMed

    Rodrigues, L O; Russo, A K; Silva, A C; Piçarro, I C; Silva, F R; Zogaib, P S; Soares, D D

    1990-01-01

    The role of caffeine in improving performance in endurance exercises is controversial and its mechanism of action is not well understood. The purpose of the present study was to evaluate the effects of caffeine on the rate of perceived exertion (RPE) by exercising athletes. Six male non-smoking runners, aged 26.8 +/- 4.9 years (mean +/- SD), who had been in training continuously for at least two years before the experiment were studied. Mean maximum oxygen consumption (VO2max) was 61.21 +/- 5.36 ml kg-1 min-1. The subjects were asked to exercise on a bicycle ergometer for 3 min each at 300 and 600 kg m min-1, after which the work load was elevated to 1200 kg m min-1 and they exercised until exhaustion. In order to evaluate the effects of caffeine, the exercise was performed twice following the ingestion of 200 ml decaffeinated coffee with and without caffeine (5 mg/kg body weight). Caffeine had no significant effect on exercise time, pulmonary ventilation, oxygen consumption, carbon dioxide extraction or exchange respiratory ratio, but the RPE was significantly lower (P less than 0.05) at the work load of 1200 kg m min-1 after the ingestion of caffeine for both trials I and II. The present results suggest that metabolic acidosis and glycogen depletion were not the main causes of exhaustion. PMID:2101061

  20. Matrix Metalloproteinase 9 Exerts Antiviral Activity against Respiratory Syncytial Virus

    PubMed Central

    Dabo, Abdoulaye J.; Cummins, Neville; Eden, Edward; Geraghty, Patrick

    2015-01-01

    Increased lung levels of matrix metalloproteinase 9 (MMP9) are frequently observed during respiratory syncytial virus (RSV) infection and elevated MMP9 concentrations are associated with severe disease. However little is known of the functional role of MMP9 during lung infection with RSV. To determine whether MMP9 exerted direct antiviral potential, active MMP9 was incubated with RSV, which showed that MMP9 directly prevented RSV infectivity to airway epithelial cells. Using knockout mice the effect of the loss of Mmp9 expression was examined during RSV infection to demonstrate MMP9’s role in viral clearance and disease progression. Seven days following RSV infection, Mmp9-/- mice displayed substantial weight loss, increased RSV-induced airway hyperresponsiveness (AHR) and reduced clearance of RSV from the lungs compared to wild type mice. Although total bronchoalveolar lavage fluid (BALF) cell counts were similar in both groups, neutrophil recruitment to the lungs during RSV infection was significantly reduced in Mmp9-/- mice. Reduced neutrophil recruitment coincided with diminished RANTES, IL-1β, SCF, G-CSF expression and p38 phosphorylation. Induction of p38 signaling was required for RANTES and G-CSF expression during RSV infection in airway epithelial cells. Therefore, MMP9 in RSV lung infection significantly enhances neutrophil recruitment, cytokine production and viral clearance while reducing AHR. PMID:26284919

  1. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    PubMed Central

    Zhang, Li; Wang, Handong

    2015-01-01

    Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ). Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX. PMID:26184238

  2. Prolactin mediates neuroprotection against excitotoxicity in primary cell cultures of hippocampal neurons via its receptor.

    PubMed

    Vergara-Castañeda, E; Grattan, D R; Pasantes-Morales, H; Pérez-Domínguez, M; Cabrera-Reyes, E A; Morales, T; Cerbón, M

    2016-04-01

    Recently it has been reported that prolactin (PRL) exerts a neuroprotective effect against excitotoxicity in hippocampus in the rat in vivo models. However, the exact mechanism by which PRL mediates this effect is not completely understood. The aim of our study was to assess whether prolactin exerts neuroprotection against excitotoxicity in an in vitro model using primary cell cultures of hippocampal neurons, and to determine whether this effect is mediated via the prolactin receptor (PRLR). Primary cell cultures of rat hippocampal neurons were used in all experiments, gene expression was evaluated by RT-qPCR, and protein expression was assessed by Western blot analysis and immunocytochemistry. Cell viability was assessed by using the MTT method. The results demonstrated that PRL treatment of neurons from primary cultures did not modify cell viability, but that it exerted a neuroprotective effect, with cells treated with PRL showing a significant increase of viability after glutamate (Glu)--induced excitotoxicity as compared with neurons treated with Glu alone. Cultured neurons expressed mRNA for both PRL and its receptor (PRLR), and both PRL and PRLR expression levels changed after the excitotoxic insult. Interestingly, the PRLR protein was detected as two main isoforms of 100 and 40 kDa as compared with that expressed in hypothalamic cells, which was present only as a 30 kDa variant. On the other hand, PRL was not detected in neuron cultures, either by western blot or by immunohistochemistry. Neuroprotection induced by PRL was significantly blocked by specific oligonucleotides against PRLR, thus suggesting that the PRL role is mediated by its receptor expressed in these neurons. The overall results indicated that PRL induces neuroprotection in neurons from primary cell cultures. PMID:26874070

  3. NeuronBank: A Tool for Cataloging Neuronal Circuitry

    PubMed Central

    Katz, Paul S.; Calin-Jageman, Robert; Dhawan, Akshaye; Frederick, Chad; Guo, Shuman; Dissanayaka, Rasanjalee; Hiremath, Naveen; Ma, Wenjun; Shen, Xiuyn; Wang, Hsui C.; Yang, Hong; Prasad, Sushil; Sunderraman, Rajshekhar; Zhu, Ying

    2010-01-01

    The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models. PMID:20428500

  4. Environmental Conditions and the Occurrence of Exertional Heat Illnesses and Exertional Heat Stroke at the Falmouth Road Race

    PubMed Central

    DeMartini, Julie K.; Casa, Douglas J.; Belval, Luke N.; Crago, Arthur; Davis, Rob J.; Jardine, John J.; Stearns, Rebecca L.

    2014-01-01

    Context: The Falmouth Road Race is unique because of the environmental conditions and relatively short distance, which allow runners to maintain a high intensity for the duration of the event. Therefore, the occurrence of exertional heat illnesses (EHIs), especially exertional heat stroke (EHS), is 10 times higher than in other races. Objective: To summarize the occurrence and relationship of EHI and environmental conditions at the Falmouth Road Race. Design: Descriptive epidemiologic study. Setting: An 11.3-km (7-mile) road race in Falmouth, Massachusetts. Patients or Other Participants: Runners who sustained an EHI while participating in the Falmouth Road Race. Main Outcome Measure(s): We obtained 18 years of medical records and environmental conditions from the Falmouth Road Race and documented the incidence of EHI, specifically EHS, as related to ambient temperature (Tamb), relative humidity, and heat index (HI). Results: Average Tamb, relative humidity, and HI were 23.3 ± 2.5°C, 70 ± 16%, and 24 ± 3.5°C, respectively. Of the 393 total EHI cases observed, EHS accounted for 274 (70%). An average of 15.2 ± 13.0 EHS cases occurred each year; the incidence was 2.13 ± 1.62 cases per 1000 runners. Regression analysis revealed a relationship between the occurrence of both EHI and EHS and Tamb (R2 = 0.71, P = .001, and R2 = 0.65, P = .001, respectively) and HI (R2 = 0.76, P < .001, and R2 = 0.74, P < .001, respectively). Occurrences of EHS (24.2 ± 15.5 cases versus 9.3 ± 4.3 cases) and EHI (32.3 ± 16.3 versus 13.0 ± 4.9 cases) were higher when Tamb and HI were high compared with when Tamb and HI were low. Conclusions: Because of the environmental conditions and race duration, the Falmouth Road Race provides a unique setting for a high incidence of EHS. A clear relationship exists between environmental stress, especially as measured by Tamb and HI, and the occurrence of EHS or other EHI. Proper prevention and treatment strategies should be used during periods

  5. Serotonin modulation of cortical neurons and networks

    PubMed Central

    Celada, Pau; Puig, M. Victoria; Artigas, Francesc

    2013-01-01

    The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe

  6. Fluorescence imaging of glutamate release in neurons

    SciTech Connect

    Wang, Ziqiang; Yeung, Edward S.

    1999-12-01

    A noninvasive detection scheme based on glutamate dehydrogenase (GDH) enzymatic assay combined with microscopy was developed to measure the glutamate release in cultured cells from the central nervous system (CNS). The enzyme reaction is very specific and sensitive. The detection limit with charge-coupled device (CCD) imaging is down to {mu}M levels of glutamate with reasonable response time ({approx}30 s). The standard glutamate test shows a linear response over 3 orders of magnitude, from {mu}M to 0.1 mM range. The in vitro monitoring of glutamate release from cultured neuron cells demonstrated excellent spatial and temporal resolution. (c) 1999 Society for Applied Spectroscopy.

  7. Relationships between one-handed force exertions in all directions and their associated postures.

    PubMed

    Wilkinson, A T; Pinder, A D J; Grieve, D W

    1995-01-01

    Photographs were taken of subjects exerting in specified directions with one hand on the handle of a triaxial force measurement system. The applied forces were recorded and posture analysis was undertaken to investigate relationships between three-dimensional force exertion and posture. The postural stability diagram, which in previous studies has been applied to fore-and-aft exertions, was applied to the vertical plane containing the manual force vector and to the horizontal plane. The vertical plane analysis provided an insight into postures associated with weak and strong exertion. The horizontal plane analysis emphasized the importance of developing torque as well as thrust at the foot base in order to exert laterally directed forces. Exertions involving a right or left component were associated with a horizontal moment at the feet of the order of 50 Nm. This moment is an important factor in the demands made upon the body during asymmetrical exertion, and the mechanisms for achieving it deserve further investigation. RELEVANCE: Exertion is not normally restricted to the sagittal plane. The approach adopted in this paper gives an insight into how body deployment relates to the direction and magnitude of exertion. Biomechanical models of asymmetric exertion should reflect the principles that have emerged. PMID:11415527

  8. Navigational path integration by cortical neurons: origins in higher-order direction selectivity

    PubMed Central

    Page, William K.; Sato, Nobuya; Froehler, Michael T.; Vaughn, William

    2015-01-01

    Navigation relies on the neural processing of sensory cues about observer self-movement and spatial location. Neurons in macaque dorsal medial superior temporal cortex (MSTd) respond to visual and vestibular self-movement cues, potentially contributing to navigation and orientation. We moved monkeys on circular paths around a room while recording the activity of MSTd neurons. MSTd neurons show a variety of sensitivities to the monkey's heading direction, circular path through the room, and place in the room. Changing visual cues alters the relative prevalence of those response properties. Disrupting the continuity of self-movement paths through the environment disrupts path selectivity in a manner linked to the time course of single neuron responses. We hypothesize that sensory cues interact with the spatial and temporal integrative properties of MSTd neurons to derive path selectivity for navigational path integration supporting spatial orientation. PMID:25589586

  9. Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons

    PubMed Central

    Müller, Jan; Bakkum, Douglas J.; Hierlemann, Andreas

    2012-01-01

    We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal–oxide–semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a “knob” to tune information processing in the network. PMID:23335887

  10. Mirror Neurons in a New World Monkey, Common Marmoset

    PubMed Central

    Suzuki, Wataru; Banno, Taku; Miyakawa, Naohisa; Abe, Hiroshi; Goda, Naokazu; Ichinohe, Noritaka

    2015-01-01

    Mirror neurons respond when executing a motor act and when observing others' similar act. So far, mirror neurons have been found only in macaques, humans, and songbirds. To investigate the degree of phylogenetic specialization of mirror neurons during the course of their evolution, we determined whether mirror neurons with similar properties to macaques occur in a New World monkey, the common marmoset (Callithrix jacchus). The ventral premotor cortex (PMv), where mirror neurons have been reported in macaques, is difficult to identify in marmosets, since no sulcal landmarks exist in the frontal cortex. We addressed this problem using “in vivo” connection imaging methods. That is, we first identified cells responsive to others' grasping action in a clear landmark, the superior temporal sulcus (STS), under anesthesia, and injected fluorescent tracers into the region. By fluorescence stereomicroscopy, we identified clusters of labeled cells in the ventrolateral frontal cortex, which were confirmed to be within the ventrolateral frontal cortex including PMv after sacrifice. We next implanted electrodes into the ventrolateral frontal cortex and STS and recorded single/multi-units under an awake condition. As a result, we found neurons in the ventrolateral frontal cortex with characteristic “mirror” properties quite similar to those in macaques. This finding suggests that mirror neurons occur in a common ancestor of New and Old World monkeys and its common properties are preserved during the course of primate evolution. PMID:26696817

  11. Neuronal migration disorders: Focus on the cytoskeleton and epilepsy.

    PubMed

    Stouffer, Melissa A; Golden, Jeffrey A; Francis, Fiona

    2016-08-01

    A wide spectrum of focal, regional, or diffuse structural brain abnormalities, collectively known as malformations of cortical development (MCDs), frequently manifest with intellectual disability (ID), epilepsy, and/or autistic spectrum disorder (ASD). As the acronym suggests, MCDs are perturbations of the normal architecture of the cerebral cortex and hippocampus. The pathogenesis of these disorders remains incompletely understood; however, one area that has provided important insights has been the study of neuronal migration. The amalgamation of human genetics and experimental studies in animal models has led to the recognition that common genetic causes of neurodevelopmental disorders, including many severe epilepsy syndromes, are due to mutations in genes regulating the migration of newly born post-mitotic neurons. Neuronal migration genes often, though not exclusively, code for proteins involved in the function of the cytoskeleton. Other cellular processes, such as cell division and axon/dendrite formation, which similarly depend on cytoskeletal functions, may also be affected. We focus here on how the susceptibility of the highly organized neocortex and hippocampus may be due to their laminar organization, which involves the tight regulation, both temporally and spatially, of gene expression, specialized progenitor cells, the migration of neurons over large distances and a birthdate-specific layering of neurons. Perturbations in neuronal migration result in abnormal lamination, neuronal differentiation defects, abnormal cellular morphology and circuit formation. Ultimately this results in disorganized excitatory and inhibitory activity leading to the symptoms observed in individuals with these disorders. PMID:26299390

  12. Physiological and Perceived Exertion Responses during International Karate Kumite Competition

    PubMed Central

    Tabben, Montassar; Sioud, Rim; Haddad, Monoem; Franchini, Emerson; Chaouachi, Anis; Coquart, Jeremy; Chaabane, Helmi; Chamari, Karim; Tourny-Chollet, Claire

    2013-01-01

    Purpose Investigate the physiological responses and rating of perceived exertion (RPE) in elite karate athletes and examine the relationship between a subjective method (Session-RPE) and two objective heart-rate (HR)-based methods to quantify training-load (TL) during international karate competition. Methods Eleven karatekas took part in this study, but only data from seven athletes who completed three matches in an international tournament were used (four men and three women). The duration of combat was 3 min for men and 2 min for women, with 33.6±7.6 min for the first interval period (match 1–2) and 14.5±3.1 min for the second interval period (match 2–3). HR was continuously recorded during each combat. Blood lactate [La-] and (RPE) were measured just before the first match and immediately after each match. Results Means total fights time, HR, %HRmax, [La-], and session-RPE were 4.7±1.6 min, 182±9 bpm, 91±3%, 9.02±2.12 mmol.L-1 and 4.2±1.2, respectively. No significant differences in %HRmax, [La-], and RPE were noticed across combats. Significant correlations were observed between RPE and both resting HR (r=0.60; P=0.004) and mean HR (r=0.64; P=0.02), session-RPE and Banister training-impulse (TRIMP) (r=0.84; P<0.001) and Edwards TL (r=0.77; P<0.01). Conclusion International karate competition elicited near-maximal cardiovascular responses and high [La-]. Training should therefore include exercise bouts that sufficiently stimulate the zone between 90 and 100% HRmax. Karate coaches could use the RPE-method to follow competitor's competition loads and consider it in their technical and tactical training. PMID:24800001

  13. Isolated Chronic Exertional Compartment Syndrome of the Lateral Lower Leg

    PubMed Central

    van Zantvoort, Aniek P.M.; de Bruijn, Johan A.; Winkes, Michiel B.; Dielemans, Jeanne P.; van der Cruijsen-Raaijmakers, Marike; Hoogeveen, Adwin R.; Scheltinga, Marc R.

    2015-01-01

    Background: Exercise-induced lower leg pain may be caused by chronic exertional compartment syndrome (CECS). The anterior (ant-CECS) or deep posterior compartment (dp-CECS) is usually affected. Knowledge regarding CECS of the lateral compartment (lat-CECS) is limited. Purpose: To describe demographic characteristics and symptoms in a consecutive series of patients with isolated CECS of the lateral compartment of the leg. Study Design: Case series; Level of evidence, 4. Methods: Since 2001, patients undergoing dynamic intracompartmental pressure (ICP) measurements for suspected CECS in a single institution were prospectively monitored. Individuals with a history possibly associated with lat-CECS and elevated ICP measurements (Pedowitz criteria) were identified. Exclusion criteria were concomitant ipsilateral ant-CECS/dp-CECS, acute compartment syndrome, recent significant trauma, peroneal nerve entrapment, or vascular claudication. Results: During an 11-year time period, a total of 26 patients with isolated lat-CECS fulfilled study criteria (15 females; median age, 21 years; range, 14-48 years). Frequently identified provocative sports were running (n = 4), walking (n = 4), field hockey (n = 3), soccer (n = 3), and volleyball (n = 2). Exercise-induced lateral lower leg pain (92%) and tightness (42%) were often reported. The syndrome was bilateral in almost two-thirds (62%, n = 16). Delay in diagnosis averaged 24 months (range, 2 months to 10 years). Conclusion: Young patients with exercise-induced pain in the lateral portions of the lower leg may suffer from isolated CECS of the lateral compartment. ICP measurements in the lateral compartment in these patients are recommended. PMID:26740955

  14. Trunk stiffness and dynamics during active extension exertions.

    PubMed

    Moorhouse, Kevin M; Granata, Kevin P

    2005-10-01

    Spinal stability is related to the recruitment and control of active muscle stiffness. Stochastic system identification techniques were used to calculate the effective stiffness and dynamics of the trunk during active trunk extension exertions. Twenty-one healthy adult subjects (10 males, 11 females) wore a harness with a cable attached to a servomotor such that isotonic flexion preloads of 100, 135, and 170 N were applied at the T10 level of the trunk. A pseudorandom stochastic force sequence (bandwidth 0-10 Hz, amplitude +/-30 N) was superimposed on the preload causing small amplitude trunk movements. Nonparametric impulse response functions of trunk dynamics were computed and revealed that the system exhibited underdamped second-order behavior. Second-order trunk dynamics were determined by calculating the best least-squares fit to the IRF. The quality of the model was quantified by comparing estimated and observed displacement variance accounted for (VAF), and quality of the second-order fits was calculated as a percentage and referred to as fit accuracy. Mean VAF and fit accuracy were 87.8 +/- 4.0% and 96.0 +/- 4.3%, respectively, indicating that the model accurately represented active trunk kinematic response. The accuracy of the kinematic representation was not influenced by preload or gender. Mean effective stiffness was 2.78 +/- 0.96 N/mm and increased significantly with preload (p < 0.001), but did not vary with gender (p = 0.425). Mean effective damping was 314 +/- 72 Ns/m and effective trunk mass was 37.0 +/- 9.3 kg. We conclude that stochastic system identification techniques should be used to calculate effective trunk stiffness and dynamics. PMID:16084200

  15. Qualitative dimensions of exertional dyspnea in adults with cystic fibrosis.

    PubMed

    Quon, Bradley S; Wilkie, Sabrina S; Ramsook, Andrew H; Schaeffer, Michele R; Puyat, Joseph H; Wilcox, Pearce G; Guenette, Jordan A

    2016-08-01

    No studies of cystic fibrosis (CF) have systematically characterized the evolution of the qualitative dimensions of exertional dyspnea. Adults with CF (n = 25) and control individuals matched for sex, age, and body mass index (n = 25) underwent cardiopulmonary cycle exercise testing with a detailed evaluation of ventilatory and dyspnea responses. The qualitative dimensions of dyspnea were examined during each exercise stage by having subjects select phrases that best described their breathing (i.e., "work/effort," "unsatisfied inspiration," and "unsatisfied expiration"). Subjects also selected phrases that described the quality of their breathing at peak exercise using an established 15-item questionnaire, which was then clustered into different categories. Subjects with CF had greater ventilatory requirements, higher end-inspiratory and end-expiratory lung volumes (% total lung capacity), and an earlier inflection/plateau in tidal volume during exercise compared with control subjects. Increased work/effort was the dominant qualitative descriptor in both groups throughout exercise. Unsatisfied inspiration was selected by 48% of subjects with CF and 40% of controls at some point during exercise. The onset of unsatisfied inspiration in these subjects occurred at a significantly lower relative exercise intensity in subjects with CF vs. controls (72 ± 21 vs. 94 ± 11% Wmax, P < 0.01). Chest tightness was the only qualitative descriptor cluster that was selected more frequently by subjects with CF vs. controls (36 vs. 0%, respectively, P < 0.05) at peak exercise. Therapeutic interventions that reduce ventilatory requirements and improve lung volumes may delay the onset of distressing sensations such as unsatisfied inspiration and chest tightness in adults with CF. PMID:27311438

  16. Neuronal avalanches and learning

    NASA Astrophysics Data System (ADS)

    de Arcangelis, Lucilla

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  17. Septo-temporal gradients of neurogenesis and activity in 13-month-old rats

    PubMed Central

    Snyder, Jason S.; Ramchand, Preethi; Rabbett, Sarah; Radik, Ruvim; Wojtowicz, J. Martin; Cameron, Heather A.

    2009-01-01

    Recent studies suggest that hippocampal function is partially dissociable along its septo-temporal axis: the septal hippocampus is more critical for spatial processing, while the temporal hippocampus may be more important for non-spatial-related behavior. In young adults, water maze training specifically activates new neurons in the temporal hippocampus but it is unknown whether subregional differences are maintained in older animals, which have reduced neurogenesis levels. We therefore examined gradients of activity-related Fos expression and neurogenesis in 13-month-old rats and found that neurogenesis occurs relatively evenly throughout the dentate gyrus. Water maze experience significantly increased Fos expression in the suprapyramidal blade and Fos was highest in the septal pole of the dentate gyrus whether the animal learned a platform location, swam in the absence of a platform or remained in their cage. No Fos+ young neurons were found using typical markers of immature neurons. However, Fos expression in the subgranular zone, where adult-born neurons predominate, was disproportionally high in the temporal dentate gyrus. These findings indicate that adult-born neurons in the temporal hippocampus are preferentially activated compared with older neurons. PMID:19632743

  18. Retinoic acid affects calcium signaling in adult molluscan neurons.

    PubMed

    Vesprini, Nicholas D; Dawson, Taylor F; Yuan, Ye; Bruce, Doug; Spencer, Gaynor E

    2015-01-01

    Retinoic acid, the active metabolite of vitamin A, is important for nervous system development, regeneration, as well as cognitive functions of the adult central nervous system. These central nervous system functions are all highly dependent on neuronal activity. Retinoic acid has previously been shown to induce changes in the firing properties and action potential waveforms of adult molluscan neurons in a dose- and isomer-dependent manner. In this study, we aimed to determine the cellular pathways by which retinoic acid might exert such effects, by testing the involvement of pathways previously shown to be affected by retinoic acid. We demonstrated that the ability of all-trans retinoic acid (atRA) to induce electrophysiological changes in cultured molluscan neurons was not prevented by inhibitors of protein synthesis, protein kinase A or phospholipase C. However, we showed that atRA was capable of rapidly reducing intracellular calcium levels in the same dose- and isomer-dependent manner as shown previously for changes in neuronal firing. Moreover, we also demonstrated that the transmembrane ion flux through voltage-gated calcium channels was rapidly modulated by retinoic acid. In particular, the peak current density was reduced and the inactivation rate was increased in the presence of atRA, over a similar time course as the changes in cell firing and reductions in intracellular calcium. These studies provide further evidence for the ability of atRA to induce rapid effects in mature neurons. PMID:25343782

  19. Serotonergic neuron regulation informed by in vivo single-cell transcriptomics.

    PubMed

    Spaethling, Jennifer M; Piel, David; Dueck, Hannah; Buckley, Peter T; Morris, Jacqueline F; Fisher, Stephen A; Lee, Jaehee; Sul, Jai-Yoon; Kim, Junhyong; Bartfai, Tamas; Beck, Sheryl G; Eberwine, James H

    2014-02-01

    Despite the recognized importance of the dorsal raphe (DR) serotonergic (5-HT) nuclei in the pathophysiology of depression and anxiety, the molecular components/putative drug targets expressed by these neurons are poorly characterized. Utilizing the promoter of an ETS domain transcription factor that is a stable marker of 5-HT neurons (Pet-1) to drive 5-HT neuronal expression of YFP, we identified 5-HT neurons in live acute slices. We isolated RNA from single 5-HT neurons in the ventromedial and lateral wings of the DR and performed single-cell RNA-Seq analysis identifying >500 G-protein coupled receptors (GPCRs) including receptors for classical transmitters, lipid signals, and peptides as well as dozens of orphan-GPCRs. Using these data to inform our selection of receptors to assess, we found that oxytocin and lysophosphatidic acid 1 receptors are translated and active in costimulating, with the α1-adrenergic receptor, the firing of DR 5-HT neurons, while the effects of histamine are inhibitory and exerted at H3 histamine receptors. The inhibitory histamine response provides evidence for tonic in vivo histamine inhibition of 5-HT neurons. This study illustrates that unbiased single-cell transcriptomics coupled with functional analyses provides novel insights into how neurons and neuronal systems are regulated. PMID:24192459

  20. Use of human induced pluripotent stem cell-derived neurons as a model for Cerebral Toxoplasmosis.

    PubMed

    Tanaka, Naomi; Ashour, Danah; Dratz, Edward; Halonen, Sandra

    2016-01-01

    Toxoplasma gondii is a ubiquitous protozoan parasite with approximately one-third of the worlds' population chronically infected. In chronically infected individuals, the parasite resides primarily in cysts within neurons in the central nervous system. The chronic infection in immunocompetent individuals has been considered to be asymptomatic but increasing evidence indicates the chronic infection can lead to neuropsychiatric disorders such as Schizophrenia, prenatal depression and suicidal thoughts. A better understanding of the mechanism(s) by which the parasite exerts effects on human behavior is limited due to lack of suitable human neuronal models. In this paper, we report the use of human neurons derived from normal cord blood CD34+ cells generated via genetic reprogramming, as an in vitro model for the study T. gondii in neurons. This culture method resulted in a relatively pure monolayer of induced human neuronal-like cells that stained positive for neuronal markers, MAP2, NFL, NFH and NeuN. These induced human neuronal-like cells (iHNs) were efficiently infected by the Prugniad strain of the parasite and supported replication of the tachyzoite stage and development of the cyst stage. Infected iHNs could be maintained through 5 days of infection, allowing for formation of large cysts. This induced human neuronal model represents a novel culture method to study both tachyzoite and bradyzoite stages of T. gondii in human neurons. PMID:27083472

  1. GABA regulates synaptic integration of newly generated neurons in the adult brain

    NASA Astrophysics Data System (ADS)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  2. BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB

    NASA Technical Reports Server (NTRS)

    Hu, Peter; Kalb, Robert G.; Walton, K. D. (Principal Investigator)

    2003-01-01

    The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.

  3. Neuronal soma-satellite glial cell interactions in sensory ganglia and the participation of purinergic receptors

    PubMed Central

    Gu, Yanping; Chen, Yong; Zhang, Xiaofei; Li, GuangWen; Wang, Cong Ying; Huang, Li-Yen Mae

    2011-01-01

    It has been known for some time that the somata of neurons in sensory ganglia respond to electrical or chemical stimulation and release transmitters in a Ca2+-dependent manner. The function of the somatic release has not been well delineated. A unique characteristic of the ganglia is that each neuronal soma is tightly enwrapped by satellite glial cells (SGCs). The somatic membrane of a sensory neuron rarely makes synaptic contact with another neuron. As a result, the influence of somatic release on the activity of adjacent neurons is likely to be indirect and/or slow. Recent studies of neuron-SGC interactions have demonstrated that ATP released from the somata of dorsal root ganglion neurons activates SGCs. They in turn exert complex excitatory and inhibitory modulation of neuronal activity. Thus, SGCs are actively involved in the processing of afferent information. In this review, we summarize our understanding of bidirectional communication between neuronal somata and SGCs in sensory ganglia and its possible role in afferent signaling under normal and injurious conditions. The participation of purinergic receptors is emphasized because of their dominant roles in the communication. PMID:20604979

  4. Temporal Hebbian plasticity designed for efficient competitive learning

    NASA Astrophysics Data System (ADS)

    Cho, Myoung Won

    2014-04-01

    Understanding the functional roles of temporal Hebbian plasticity has been of growing interest since several experiments revealed that the change in synaptic efficacy was determined by the precise temporal relation between post- and presynaptic spikes. We here investigate the learning properties of the typical synaptic modification forms. We explain how the peculiar characteristics in synaptic modification, such as asymmetry, decay rate, and oscillatory behavior, exert effects on the direction and the performance of network formation. Also, we argue that the aforementioned characteristics help to achieve proper network adaptation, such as activity-dependent columnar organization, through an efficient competitive learning process.

  5. Changes in the selection differential exerted on a marine snail during the ontogeny of a predatory shore crab.

    PubMed

    Pakes, D; Boulding, E G

    2010-08-01

    Empirical estimates of selection gradients caused by predators are common, yet no one has quantified how these estimates vary with predator ontogeny. We used logistic regression to investigate how selection on gastropod shell thickness changed with predator size. Only small and medium purple shore crabs (Hemigrapsus nudus) exerted a linear selection gradient for increased shell-thickness within a single population of the intertidal snail (Littorina subrotundata). The shape of the fitness function for shell thickness was confirmed to be linear for small and medium crabs but was humped for large male crabs, suggesting no directional selection. A second experiment using two prey species to amplify shell thickness differences established that the selection differential on adult snails decreased linearly as crab size increased. We observed differences in size distribution and sex ratios among three natural shore crab populations that may cause spatial and temporal variation in predator-mediated selection on local snail populations. PMID:20524948

  6. Gravitational moment exerted on a small body by an oblate body

    NASA Technical Reports Server (NTRS)

    Roithmayr, Carlos M.

    1989-01-01

    The present demonstration of a method for obtaining vector-dyadic expressions of the gravitational moment about a body's center-of-mass proceeds through the derivation of an expression for the gravitational moment exerted by an oblate spheroid. The contribution of the earth's oblateness to the gravitational moment exerted on a body has been numerically evaluated for a greatly simplified illustrative case; this contribution is noted to be significant by comparison with such other external moments as those exerted by aerodynamic forces.

  7. Kappe neurons, a novel population of olfactory sensory neurons

    PubMed Central

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-01-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system. PMID:24509431

  8. Kappe neurons, a novel population of olfactory sensory neurons

    NASA Astrophysics Data System (ADS)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  9. Midline thalamic neurons are differentially engaged during hippocampus network oscillations.

    PubMed

    Lara-Vásquez, Ariel; Espinosa, Nelson; Durán, Ernesto; Stockle, Marcelo; Fuentealba, Pablo

    2016-01-01

    The midline thalamus is reciprocally connected with the medial temporal lobe, where neural circuitry essential for spatial navigation and memory formation resides. Yet, little information is available on the dynamic relationship between activity patterns in the midline thalamus and medial temporal lobe. Here, we report on the functional heterogeneity of anatomically-identified thalamic neurons and the differential modulation of their activity with respect to dorsal hippocampal rhythms in the anesthetized mouse. Midline thalamic neurons expressing the calcium-binding protein calretinin, irrespective of their selective co-expression of calbindin, discharged at overall low levels, did not increase their activity during hippocampal theta oscillations, and their firing rates were inhibited during hippocampal sharp wave-ripples. Conversely, thalamic neurons lacking calretinin discharged at higher rates, increased their activity during hippocampal theta waves, but remained unaffected during sharp wave-ripples. Our results indicate that the midline thalamic system comprises at least two different classes of thalamic projection neuron, which can be partly defined by their differential engagement by hippocampal pathways during specific network oscillations that accompany distinct behavioral contexts. Thus, different midline thalamic neuronal populations might be selectively recruited to support distinct stages of memory processing, consistent with the thalamus being pivotal in the dialogue of cortical circuits. PMID:27411890

  10. Quantifying bursting neuron activity from calcium signals using blind deconvolution.

    PubMed

    Park, In Jun; Bobkov, Yuriy V; Ache, Barry W; Principe, Jose C

    2013-09-15

    Advances in calcium imaging have enabled studies of the dynamic activity of both individual neurons and neuronal assemblies. However, challenges, such as unknown nonlinearities in the spike-calcium relationship, noise, and the often relatively low temporal resolution of the calcium signal compared to the time-scale of spike generation, restrict the accurate estimation of action potentials from the calcium signal. Complex neuronal discharge, such as the activity demonstrated by bursting and rhythmically active neurons, represents an even greater challenge for reconstructing spike trains based on calcium signals. We propose a method using blind calcium signal deconvolution based on an information-theoretic approach. This model is meant to maximise the output entropy of a nonlinear filter where the nonlinearity is defined by the cumulative distribution function of the spike signal. We tested our maximum entropy (ME) algorithm using bursting olfactory receptor neurons (bORNs) of the lobster olfactory organ. The advantage of the ME algorithm is that the filter can be trained online based only on the statistics of the spike signal, without any assumptions regarding the unknown transfer function characterizing the relation between the spike and calcium signal. We show that the ME method is able to more accurately reconstruct the timing of the first and last spikes of a burst compared to other methods and that it improves the temporal precision fivefold compared to direct timing resolution of calcium signal. PMID:23711821

  11. Midline thalamic neurons are differentially engaged during hippocampus network oscillations

    PubMed Central

    Lara-Vásquez, Ariel; Espinosa, Nelson; Durán, Ernesto; Stockle, Marcelo; Fuentealba, Pablo

    2016-01-01

    The midline thalamus is reciprocally connected with the medial temporal lobe, where neural circuitry essential for spatial navigation and memory formation resides. Yet, little information is available on the dynamic relationship between activity patterns in the midline thalamus and medial temporal lobe. Here, we report on the functional heterogeneity of anatomically-identified thalamic neurons and the differential modulation of their activity with respect to dorsal hippocampal rhythms in the anesthetized mouse. Midline thalamic neurons expressing the calcium-binding protein calretinin, irrespective of their selective co-expression of calbindin, discharged at overall low levels, did not increase their activity during hippocampal theta oscillations, and their firing rates were inhibited during hippocampal sharp wave-ripples. Conversely, thalamic neurons lacking calretinin discharged at higher rates, increased their activity during hippocampal theta waves, but remained unaffected during sharp wave-ripples. Our results indicate that the midline thalamic system comprises at least two different classes of thalamic projection neuron, which can be partly defined by their differential engagement by hippocampal pathways during specific network oscillations that accompany distinct behavioral contexts. Thus, different midline thalamic neuronal populations might be selectively recruited to support distinct stages of memory processing, consistent with the thalamus being pivotal in the dialogue of cortical circuits. PMID:27411890

  12. Imaging voltage in neurons

    PubMed Central

    Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael

    2011-01-01

    In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles and intrinsic approaches), and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic or electro-optical phenomena, to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods. PMID:21220095

  13. Active engagement improves primary auditory cortical neurons’ ability to discriminate temporal modulation

    PubMed Central

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

    2012-01-01

    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 non-synchronized and synchronized responses, the firing rate of non-synchronized 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 where rate and temporal coding work in parallel, permitting a multiplexed code for temporal modulation, and for a complementary representation of rate and temporal coding. PMID:22764239

  14. Josephson junction simulation of neurons

    NASA Astrophysics Data System (ADS)

    Crotty, Patrick; Schult, Dan; Segall, Ken

    2010-07-01

    With the goal of understanding the intricate behavior and dynamics of collections of neurons, we present superconducting circuits containing Josephson junctions that model biologically realistic neurons. These “Josephson junction neurons” reproduce many characteristic behaviors of biological neurons such as action potentials, refractory periods, and firing thresholds. They can be coupled together in ways that mimic electrical and chemical synapses. Using existing fabrication technologies, large interconnected networks of Josephson junction neurons would operate fully in parallel. They would be orders of magnitude faster than both traditional computer simulations and biological neural networks. Josephson junction neurons provide a new tool for exploring long-term large-scale dynamics for networks of neurons.

  15. Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases

    PubMed Central

    Crippa, Valeria; D’Agostino, Vito G.; Cristofani, Riccardo; Rusmini, Paola; Cicardi, Maria E.; Messi, Elio; Loffredo, Rosa; Pancher, Michael; Piccolella, Margherita; Galbiati, Mariarita; Meroni, Marco; Cereda, Cristina; Carra, Serena; Provenzani, Alessandro; Poletti, Angelo

    2016-01-01

    Neurodegenerative diseases (NDs) are often associated with the presence of misfolded protein inclusions. The chaperone HSPB8 is upregulated in mice, the human brain and muscle structures affected during NDs progression. HSPB8 exerts a potent pro-degradative activity on several misfolded proteins responsible for familial NDs forms. Here, we demonstrated that HSPB8 also counteracts accumulation of aberrantly localized misfolded forms of TDP-43 and its 25 KDa fragment involved in most sporadic cases of Amyotrophic Lateral Sclerosis (sALS) and of Fronto Lateral Temporal Dementia (FLTD). HSPB8 acts with BAG3 and the HSP70/HSC70-CHIP complex enhancing the autophagic removal of misfolded proteins. We performed a high-through put screening (HTS) to find small molecules capable of inducing HSPB8 in neurons for therapeutic purposes. We identified two compounds, colchicine and doxorubicin, that robustly up-regulated HSPB8 expression. Both colchicine and doxorubicin increased the expression of the master regulator of autophagy TFEB, the autophagy linker p62/SQSTM1 and the autophagosome component LC3. In line, both drugs counteracted the accumulation of TDP-43 and TDP-25 misfolded species responsible for motoneuronal death in sALS. Thus, analogs of colchicine and doxorubicin able to induce HSPB8 and with better safety and tolerability may result beneficial in NDs models. PMID:26961006

  16. Representation of interval timing by temporally scalable firing patterns in rat prefrontal cortex

    PubMed Central

    Xu, Min; Zhang, Si-yu; Dan, Yang; Poo, Mu-ming

    2014-01-01

    Perception of time interval on the order of seconds is an essential component of cognition, but the underlying neural mechanism remains largely unknown. In rats trained to estimate time intervals, we found that many neurons in the medial prefrontal cortex (PFC) exhibited sustained spiking activity with diverse temporal profiles of firing-rate modulation during the time-estimation period. Interestingly, in tasks involving different intervals, each neuron exhibited firing-rate modulation with the same profile that was temporally scaled by a factor linearly proportional to the instructed intervals. The behavioral variability across trials within each task also correlated with the intertrial variability of the temporal scaling factor. Local cooling of the medial PFC, which affects neural circuit dynamics, significantly delayed behavioral responses. Thus, PFC neuronal activity contributes to time perception, and temporally scalable firing-rate modulation may reflect a general mechanism for neural representation of interval timing. PMID:24367075

  17. Representation of interval timing by temporally scalable firing patterns in rat prefrontal cortex.

    PubMed

    Xu, Min; Zhang, Si-yu; Dan, Yang; Poo, Mu-ming

    2014-01-01

    Perception of time interval on the order of seconds is an essential component of cognition, but the underlying neural mechanism remains largely unknown. In rats trained to estimate time intervals, we found that many neurons in the medial prefrontal cortex (PFC) exhibited sustained spiking activity with diverse temporal profiles of firing-rate modulation during the time-estimation period. Interestingly, in tasks involving different intervals, each neuron exhibited firing-rate modulation with the same profile that was temporally scaled by a factor linearly proportional to the instructed intervals. The behavioral variability across trials within each task also correlated with the intertrial variability of the temporal scaling factor. Local cooling of the medial PFC, which affects neural circuit dynamics, significantly delayed behavioral responses. Thus, PFC neuronal activity contributes to time perception, and temporally scalable firing-rate modulation may reflect a general mechanism for neural representation of interval timing. PMID:24367075

  18. Nonexocytotic serotonin release tonically suppresses serotonergic neuron activity

    PubMed Central

    Montalbano, Alberto; Baccini, Gilda; Tatini, Francesca; Palmini, Rolando Berlinguer; Corradetti, Renato

    2015-01-01

    The firing activity of serotonergic neurons in raphe nuclei is regulated by negative feedback exerted by extracellular serotonin (5-HT)o acting through somatodendritic 5-HT1A autoreceptors. The steady-state [5-HT]o, sensed by 5-HT1A autoreceptors, is determined by the balance between the rates of 5-HT release and reuptake. Although it is well established that reuptake of 5-HTo is mediated by 5-HT transporters (SERT), the release mechanism has remained unclear. It is also unclear how selective 5-HT reuptake inhibitor (SSRI) antidepressants increase the [5-HT]o in raphe nuclei and suppress serotonergic neuron activity, thereby potentially diminishing their own therapeutic effect. Using an electrophysiological approach in a slice preparation, we show that, in the dorsal raphe nucleus (DRN), continuous nonexocytotic 5-HT release is responsible for suppression of phenylephrine-facilitated serotonergic neuron firing under basal conditions as well as for autoinhibition induced by SSRI application. By using 5-HT1A autoreceptor-activated G protein–gated inwardly rectifying potassium channels of patched serotonergic neurons as 5-HTo sensors, we show substantial nonexocytotic 5-HT release under conditions of abolished firing activity, Ca2+ influx, vesicular monoamine transporter 2–mediated vesicular accumulation of 5-HT, and SERT-mediated 5-HT transport. Our results reveal a cytosolic origin of 5-HTo in the DRN and suggest that 5-HTo may be supplied by simple diffusion across the plasma membrane, primarily from the dense network of neurites of serotonergic neurons surrounding the cell bodies. These findings indicate that the serotonergic system does not function as a sum of independently acting neurons but as a highly interdependent neuronal network, characterized by a shared neurotransmitter pool and the regulation of firing activity by an interneuronal, yet activity-independent, nonexocytotic mechanism. PMID:25712017

  19. Amitriptyline Activates TrkA to Aid Neuronal Growth and Attenuate Anesthesia-Induced Neurodegeneration in Rat Dorsal Root Ganglion Neurons.

    PubMed

    Zheng, Xiaochun; Chen, Feng; Zheng, Ting; Huang, Fengyi; Chen, Jianghu; Tu, Wenshao

    2016-05-01

    Tricyclic antidepressant amitriptyline (AM) has been shown to exert neurotrophic activity on neurons. We thus explored whether AM may aid the neuronal development and protect anesthesia-induced neuro-injury in young spinal cord dorsal root ganglion (DRG) neurons.The DRG explants were prepared from 1-day-old rats. The effect of AM on aiding DRG neural development was examined by immunohistochemistry at dose-dependent manner. AM-induced changes in gene and protein expressions, and also phosphorylation states of tyrosine kinases receptor A (TrkA) and B (TrkB) in DRG, were examined by quantitative real-time polymerase chain reaction and western blot. The effect of AM on attenuating lidocaine-induced DRG neurodegeneration was examined by immunohistochemistry, and small interfering RNA (siRNA)-mediated TrkA/B down-regulation.Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10 M. AM activated TrkA in DRG through phosphorylation, whereas it had little effect on TrkB-signaling pathway. AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones. Moreover, the neuroprotection of AM on lidocaine-injured neurodegeneration was blocked by siRNA-mediated TrkA down-regulation, but not by TrkB down-regulation.Amitriptyline facilitated neuronal development and had protective effect on lidocaine-induced neurodegeneration, very likely through the activation of TrkA-signaling pathway in DRG. PMID:27149473

  20. Amitriptyline Activates TrkA to Aid Neuronal Growth and Attenuate Anesthesia-Induced Neurodegeneration in Rat Dorsal Root Ganglion Neurons

    PubMed Central

    Zheng, Xiaochun; Chen, Feng; Zheng, Ting; Huang, Fengyi; Chen, Jianghu; Tu, Wenshao

    2016-01-01

    Abstract Tricyclic antidepressant amitriptyline (AM) has been shown to exert neurotrophic activity on neurons. We thus explored whether AM may aid the neuronal development and protect anesthesia-induced neuro-injury in young spinal cord dorsal root ganglion (DRG) neurons. The DRG explants were prepared from 1-day-old rats. The effect of AM on aiding DRG neural development was examined by immunohistochemistry at dose-dependent manner. AM-induced changes in gene and protein expressions, and also phosphorylation states of tyrosine kinases receptor A (TrkA) and B (TrkB) in DRG, were examined by quantitative real-time polymerase chain reaction and western blot. The effect of AM on attenuating lidocaine-induced DRG neurodegeneration was examined by immunohistochemistry, and small interfering RNA (siRNA)-mediated TrkA/B down-regulation. Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10 M. AM activated TrkA in DRG through phosphorylation, whereas it had little effect on TrkB-signaling pathway. AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones. Moreover, the neuroprotection of AM on lidocaine-injured neurodegeneration was blocked by siRNA-mediated TrkA down-regulation, but not by TrkB down-regulation. Amitriptyline facilitated neuronal development and had protective effect on lidocaine-induced neurodegeneration, very likely through the activation of TrkA-signaling pathway in DRG. PMID:27149473

  1. Supramolecular nanoparticles that target phosphatidylinositol-3-kinase overcome insulin resistance and exert pronounced antitumor efficacy

    PubMed Central

    Kulkarni, Ashish A.; Roy, Bhaskar; Rao, Poornima S.; Wyant, Gregory A.; Mahmoud, Ayaat; Ramachandran, Madhumitha; Sengupta, Poulomi; Goldman, Aaron; Kotamraju, Venkata Ramana; Basu, Sudipta; Mashelkar, Raghunath A; Ruoslahti, Erkki; Dinulescu, Daniela M.; Sengupta, Shiladitya

    2013-01-01

    The centrality of phosphatidylinositol-3-kinase (PI3K) in cancer etiology is well established, but clinical translation of PI3K inhibitors has been limited by feedback signaling, suboptimal intra-tumoral concentration and an insulin resistance ‘class effect’. The current study was designed to explore the use of supramolecular nanochemistry for targeting PI3K to enhance antitumor efficacy and potentially overcome these limitations. PI3K inhibitor structures were rationally modified using a cholesterol-based derivative, facilitating supramolecular nanoassembly with L-α-phosphatidylcholine and DSPE-PEG. The supramolecular nanoparticles that were assembled were physicochemically characterized and functionally evaluated in vitro. Antitumor efficacy was quantified in vivo using 4T1 breast cancer and K-RasLSL/+/Ptenfl/fl ovarian cancer models, with effects on glucose homeostasis evaluated using an insulin sensitivity test. The use of PI103 and PI828 as surrogate molecules to engineer the supramolecular nanoparticles highlighted the need to keep design principles in perspective; specifically, potency of the active molecule and the linker chemistry were critical principles for efficacy, similar to antibody-drug conjugates. We found that the supramolecular nanoparticles exerted a temporally-sustained inhibition of phosphorylation of Akt, mTOR, S6K and 4EBP in vivo. These effects were associated with increased antitumor efficacy and survival as compared with PI103 and PI828. Efficacy was further increased by decorating the nanoparticle surface with tumor-homing peptides. Notably, the use of supramolecular nanoparticles abrogated the insulin resistance that has been associated widely with other PI3K inhibitors. This study provides a preclinical foundation for the use of supramolecular nanochemistry to overcome current challenges associated with PI3K inhibitors, offering a paradigm for extension to other molecularly targeted therapeutics being explored for cancer treatment

  2. Scalable Semisupervised Functional Neurocartography Reveals Canonical Neurons in Behavioral Networks.

    PubMed

    Frady, E Paxon; Kapoor, Ashish; Horvitz, Eric; Kristan, William B

    2016-08-01

    Large-scale data collection efforts to map the brain are underway at multiple spatial and temporal scales, but all face fundamental problems posed by high-dimensional data and intersubject variability. Even seemingly simple problems, such as identifying a neuron/brain region across animals/subjects, become exponentially more difficult in high dimensions, such as recognizing dozens of neurons/brain regions simultaneously. We present a framework and tools for functional neurocartography-the large-scale mapping of neural activity during behavioral states. Using a voltage-sensitive dye (VSD), we imaged the multifunctional responses of hundreds of leech neurons during several behaviors to identify and functionally map homologous neurons. We extracted simple features from each of these behaviors and combined them with anatomical features to create a rich medium-dimensional feature space. This enabled us to use machine learning techniques and visualizations to characterize and account for intersubject variability, piece together a canonical atlas of neural activity, and identify two behavioral networks. We identified 39 neurons (18 pairs, 3 unpaired) as part of a canonical swim network and 17 neurons (8 pairs, 1 unpaired) involved in a partially overlapping preparatory network. All neurons in the preparatory network rapidly depolarized at the onsets of each behavior, suggesting that it is part of a dedicated rapid-response network. This network is likely mediated by the S cell, and we referenced VSD recordings to an activity atlas to identify multiple cells of interest simultaneously in real time for further experiments. We targeted and electrophysiologically verified several neurons in the swim network and further showed that the S cell is presynaptic to multiple neurons in the preparatory network. This study illustrates the basic framework to map neural activity in high dimensions with large-scale recordings and how to extract the rich information necessary to perform

  3. Control of Granule Cell Dispersion by Natural Materials Such as Eugenol and Naringin: A Potential Therapeutic Strategy Against Temporal Lobe Epilepsy.

    PubMed

    Kim, Sang Ryong

    2016-08-01

    The hippocampus is an important brain area where abnormal morphological characteristics are often observed in patients with temporal lobe epilepsy (TLE), typically showing the loss of the principal neurons in the CA1 and CA3 areas of the hippocampus. TLE is frequently associated with widening of the granule cell layer of the dentate gyrus (DG), termed granule cell dispersion (GCD), in the hippocampus, suggesting that the control of GCD with protection of hippocampal neurons may be useful for preventing and inhibiting epileptic seizures. We previously reported that eugenol (EUG), which is an essential component of medicinal herbs and has anticonvulsant activity, is beneficial for treating epilepsy through its ability to inhibit GCD via suppression of mammalian target of rapamycin complex 1 (mTORC1) activation in the hippocampal DG in a kainic acid (KA)-treated mouse model of epilepsy in vivo. In addition, we reported that naringin, a bioflavonoid in citrus fruits, could exert beneficial effects, such as antiautophagic stress and antineuroinflammation, in the KA mouse model of epilepsy, even though it was unclear whether naringin might also attenuate the seizure-induced morphological changes of GCD in the DG. Similar to the effects of EUG, we recently observed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which are both involved in epileptic seizures, in the hippocampus of mouse brain. Therefore, these observations suggest that the utilization of natural materials, which have beneficial properties such as inhibition of GCD formation and protection of hippocampal neurons, may be useful in developing a novel therapeutic agent against TLE. PMID:27404051

  4. Neuroprotective effect of a chuk-me-sun-dan on neurons from ischemic damage and neuronal cell toxicity.

    PubMed

    Chung, Tae-Wook; Koo, Byung-Soo; Choi, Eun-Gyu; Kim, Min-Gon; Lee, In-Seon; Kim, Cheorl-Ho

    2006-01-01

    Chukmesundan (CMSD), composed of the following 8 medicinal herbs including Panex ginseng C.A. MEYER, Atractylodes macrocephala KOID, Poria cocos WOLF, Pinellia ternata BREIT, Brassica alba BOISS, Aconitum carmichaeli DEBX, Cynanchum atratum BGE and Cuscuta chinensis LAM. CMSD is being used in Korea for the treatment of various symptoms accompanying hypertension and cerebrovascular disorders. This study was carried out to examine the effects of CMSD on cultured primary neuron cell, cell cytotoxicity and lipid peroxidation in Abeta-treated cells. Cell death was enhanced by addition of Abeta. Pretreatment of CMSD attenuated in cell killing induced by Abeta. The protective effect of the CMSD water extracts on Abeta-induced neuronal death was also observed by lactate dehydrogenase assay using cultured astrocyte cells. Abeta-induced cell death was protected by the water extract of CMSD in a dose-dependent manner, and 25-50 microg/ml was the most effective concentration. CMSD has been also shown to protect primary cultured neurons from N-methyl-D: -aspartate receptor-mediated glutamate toxicity. It was in vivo evidenced that CMSD protects neurons against ischemia-induced cell death. Moreover, oral administration of CMSD into mice prevented ischemia-induced learning disability and rescued hippocampal CA1 neurons from lethal ischemic damage. The neuroprotective action of exogenous CMSD was also confirmed by counting synapses in the hippocampal CA1 region. The presence of CMSD in neuron cultures rescued the neurons from nitrogen oxide (NO)-induced death. From these, it was suggested that CMSD may exert its neuroprotective effect by reducing the NO-mediated formation of free radicals or antagonizing their toxicity. PMID:16474991

  5. The Effect of Exertion and Sex on Vertical Ground Reaction Force Variables and Landing Mechanics.

    PubMed

    Bell, David R; Pennuto, Anthony P; Trigsted, Stephanie M

    2016-06-01

    Bell, DR, Pennuto, AP, and Trigsted, SM. The effect of exertion and sex on vertical ground reaction force variables and landing mechanics. J Strength Cond Res 30(6): 1661-1669, 2016-The purpose of this investigation was to determine how exertion and sex affected a variety of vertical ground reaction force (VGRF) parameters during a jump-landing task, including peak VGRF, peak VGRF asymmetry, loading rate, and loading rate asymmetry. Additionally, we wanted to determine whether landing mechanics changed after exertion as measured by the Landing Error Scoring System (LESS). Forty recreationally active participants (20 men and 20 women) completed jump landings from a 30-cm-high box onto force plates before and after repeated bouts of an exercise circuit until a specific rating of perceived exertion was achieved. Three-way (sex × time × limb) analyses of variance were used to analyze variables pre-exertion to postexertion. No significant 3-way interactions were observed for peak VGRF (p = 0.31) or loading rate (p = 0.14). Time by sex interactions were observed for peak VGRF (p = 0.02) and loading rate (p = 0.008). Post hoc analysis revealed that men increased landing force and loading rate after exertion while women did not. Landing mechanics, as assessed by total LESS score, were worse after exertion (p < 0.001) with increased frequency of errors for knee flexion <30° at initial contact, lateral trunk flexion, and not flexing the hip during landing. Women may be more resistant to exertion compared with men and use different joint controls' strategies to cope with VGRF after exertion. However, VGRF asymmetry is not affected by sex and exertion. Limiting peak VGRF and addressing landing postures, especially after exertion, should be components of injury prevention strategies. PMID:26562710

  6. Autapse-induced multiple coherence resonance in single neurons and neuronal networks

    PubMed Central

    Yilmaz, Ergin; Ozer, Mahmut; Baysal, Veli; Perc, Matjaž

    2016-01-01

    We study the effects of electrical and chemical autapse on the temporal coherence or firing regularity of single stochastic Hodgkin-Huxley neurons and scale-free neuronal networks. Also, we study the effects of chemical autapse on the occurrence of spatial synchronization in scale-free neuronal networks. Irrespective of the type of autapse, we observe autaptic time delay induced multiple coherence resonance for appropriately tuned autaptic conductance levels in single neurons. More precisely, we show that in the presence of an electrical autapse, there is an optimal intensity of channel noise inducing the multiple coherence resonance, whereas in the presence of chemical autapse the occurrence of multiple coherence resonance is less sensitive to the channel noise intensity. At the network level, we find autaptic time delay induced multiple coherence resonance and synchronization transitions, occurring at approximately the same delay lengths. We show that these two phenomena can arise only at a specific range of the coupling strength, and that they can be observed independently of the average degree of the network. PMID:27480120

  7. Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons.

    PubMed

    Urban, Daniel J; Zhu, Hu; Marcinkiewcz, Catherine A; Michaelides, Michael; Oshibuchi, Hidehiro; Rhea, Darren; Aryal, Dipendra K; Farrell, Martilias S; Lowery-Gionta, Emily; Olsen, Reid H J; Wetsel, William C; Kash, Thomas L; Hurd, Yasmin L; Tecott, Laurence H; Roth, Bryan L

    2016-04-01

    Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes-hours) and long period of time (days-weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons. PMID:26383016

  8. Autapse-induced multiple coherence resonance in single neurons and neuronal networks.

    PubMed

    Yilmaz, Ergin; Ozer, Mahmut; Baysal, Veli; Perc, Matjaž

    2016-01-01

    We study the effects of electrical and chemical autapse on the temporal coherence or firing regularity of single stochastic Hodgkin-Huxley neurons and scale-free neuronal networks. Also, we study the effects of chemical autapse on the occurrence of spatial synchronization in scale-free neuronal networks. Irrespective of the type of autapse, we observe autaptic time delay induced multiple coherence resonance for appropriately tuned autaptic conductance levels in single neurons. More precisely, we show that in the presence of an electrical autapse, there is an optimal intensity of channel noise inducing the multiple coherence resonance, whereas in the presence of chemical autapse the occurrence of multiple coherence resonance is less sensitive to the channel noise intensity. At the network level, we find autaptic time delay induced multiple coherence resonance and synchronization transitions, occurring at approximately the same delay lengths. We show that these two phenomena can arise only at a specific range of the coupling strength, and that they can be observed independently of the average degree of the network. PMID:27480120

  9. Genesis and Control of bursting activity in a neuronal model

    NASA Astrophysics Data System (ADS)

    Cymbalyuk, Gennady

    2005-11-01

    Neurons are observed in one of four fundamental activity modes: silence, sub-threshold oscillations, tonic spiking, and bursting. Neurons exhibit various activity regimes and regime transitions that reflect their complement of ionic channels and modulatory state. The leech presents unique opportunities for experimental and theoretical studies on the dynamics of neuronal activity. The central pattern generator controlling the leech's heartbeat contains identified pairs of mutually inhibitory neurons. Bursting activity of neurons is an oscillatory activity consisting of intervals of repetitive spiking separated by intervals of quiescence. It has been observed in neurons under normal and pathological conditions. Neurons which are capable of generating bursting activity endogenously play an important role in motor control and other brain functions. Burst duration, interburst interval and spike frequency are crucial temporal characteristics of bursting activity and thus have to be regulated. Application of the bifurcation theory of dynamical systems suggests new mechanism of how bursting activity can be generated by neurons and how burst duration can be regulated. Here we describe two mechanisms for the transition between tonic spiking and bursting. First mechanism describes a smooth, continuous and reversible transition from tonic spiking into bursting in a model neuron. The burst duration increases with no bound as 1/(a-a0)^1/2, where a0 is a parameter determining the transition. The characteristic features of this mechanism are that (a) the burst duration can be made arbitrarily long while (b) inter-burst interval does not depend on the parameter. The second mechanism is concerned with bi-stability where simultaneous tonic spiking and bursting activities co-exist in a neuron. The mechanism is based on a saddle-node periodic orbit bifurcation with non-central homoclinic orbits. This bifurcation describes a transition between three qualitatively different types of

  10. Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex.

    PubMed

    Telley, Ludovic; Govindan, Subashika; Prados, Julien; Stevant, Isabelle; Nef, Serge; Dermitzakis, Emmanouil; Dayer, Alexandre; Jabaudon, Denis

    2016-03-25

    During corticogenesis, excitatory neurons are born from progenitors located in the ventricular zone (VZ), from where they migrate to assemble into circuits. How neuronal identity is dynamically specified upon progenitor division is unknown. Here, we study this process using a high-temporal-resolution technology allowing fluorescent tagging of isochronic cohorts of newborn VZ cells. By combining this in vivo approach with single-cell transcriptomics in mice, we identify and functionally characterize neuron-specific primordial transcriptional programs as they dynamically unfold. Our results reveal early transcriptional waves that instruct the sequence and pace of neuronal differentiation events, guiding newborn neurons toward their final fate, and contribute to a road map for the reverse engineering of specific classes of cortical neurons from undifferentiated cells. PMID:26940868

  11. Differential regulation of apical-basolateral dendrite outgrowth by activity in hippocampal neurons.

    PubMed

    Yuan, Yang; Seong, Eunju; Yuan, Li; Singh, Dipika; Arikkath, Jyothi

    2015-01-01

    Hippocampal pyramidal neurons have characteristic dendrite asymmetry, characterized by structurally and functionally distinct apical and basolateral dendrites. The ability of the neuron to generate and maintain dendrite asymmetry is vital, since synaptic inputs received are critically dependent on dendrite architecture. Little is known about the role of neuronal activity in guiding maintenance of dendrite asymmetry. Our data indicate that dendrite asymmetry is established and maintained early during development. Further, our results indicate that cell intrinsic and global alterations of neuronal activity have differential effects on net extension of apical and basolateral dendrites. Thus, apical and basolateral dendrite extension may be independently regulated by cell intrinsic and network neuronal activity during development, suggesting that individual dendrites may have autonomous control over net extension. We propose that regulated individual dendrite extension in response to cell intrinsic and neuronal network activity may allow temporal control of synapse specificity in the developing hippocampus. PMID:26321915

  12. Visualization of cyclic nucleotide dynamics in neurons

    PubMed Central

    Gorshkov, Kirill; Zhang, Jin

    2014-01-01

    The second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) transduce many neuromodulatory signals from hormones and neurotransmitters into specific functional outputs. Their production, degradation and signaling are spatiotemporally regulated to achieve high specificity in signal transduction. The development of genetically encodable fluorescent biosensors has provided researchers with useful tools to study these versatile second messengers and their downstream effectors with unparalleled spatial and temporal resolution in cultured cells and living animals. In this review, we introduce the general design of these fluorescent biosensors and describe several of them in more detail. Then we discuss a few examples of using cyclic nucleotide fluorescent biosensors to study regulation of neuronal function and finish with a discussion of advances in the field. Although there has been significant progress made in understanding how the specific signaling of cyclic nucleotide second messengers is achieved, the mechanistic details in complex cell types like neurons are only just beginning to surface. Current and future fluorescent protein reporters will be essential to elucidate the role of cyclic nucleotide signaling dynamics in the functions of individual neurons and their networks. PMID:25538560

  13. The utility of cerebral blood flow imaging in patients with the unique syndrome of progressive dementia with motor neuron disease

    SciTech Connect

    Ohnishi, T.; Hoshi, H.; Jinnouchi, S.; Nagamachi, S.; Watanabe, K.; Mituyama, Y. )

    1990-05-01

    Two patients presenting with progressive dementia coupled with motor neuron disease underwent brain SPECT using N-isopropyl-p iodine-123-iodoamphetamine (({sup 123}I)IMP). The characteristic clinical features of progressive dementia and motor neuron disease were noted. IMP SPECT also revealed reduced uptake in the bilateral frontal and temporal regions, with no reduction of uptake in the parietal, parietal-occipital regions. We conclude that IMP SPECT has potential for the evaluation of progressive dementia with motor neuron disease.

  14. Temporal Organization in Prose

    ERIC Educational Resources Information Center

    Kulhavy, Raymond W.; And Others

    1977-01-01

    High school students read textual passages organized around a semantic, temporal, or random theme. Free recall, semantically, and temporally-cued tests measured recall. During free recall, the organized passages yielded greater recall. For the cued tests, more words were remembered when the passage organization matched the type of test cue.…

  15. Temporal Bisection in Children.

    ERIC Educational Resources Information Center

    Droit-Volet, Sylvie; Wearden, John H.

    2001-01-01

    Trained 3-, 5-, and 8-year-olds in temporal bisection task, with nonstandard comparison stimuli spaced linearly between short or long standard visual stimuli. Statistical analyses and results from different theoretical models of the data all suggested that temporal sensitivity was higher in the 8-year-olds than in younger groups, even when the…

  16. Microbial light-activatable proton pumps as neuronal inhibitors to functionally dissect neuronal networks in C. elegans.

    PubMed

    Husson, Steven J; Liewald, Jana F; Schultheis, Christian; Stirman, Jeffrey N; Lu, Hang; Gottschalk, Alexander

    2012-01-01

    Essentially any behavior in simple and complex animals depends on neuronal network function. Currently, the best-defined system to study neuronal circuits is the nematode Caenorhabditis elegans, as the connectivity of its 302 neurons is exactly known. Individual neurons can be activated by photostimulation of Channelrhodopsin-2 (ChR2) using blue light, allowing to directly probe the importance of a particular neuron for the respective behavioral output of the network under study. In analogy, other excitable cells can be inhibited by expressing Halorhodopsin from Natronomonas pharaonis (NpHR) and subsequent illumination with yellow light. However, inhibiting C. elegans neurons using NpHR is difficult. Recently, proton pumps from various sources were established as valuable alternative hyperpolarizers. Here we show that archaerhodopsin-3 (Arch) from Halorubrum sodomense and a proton pump from the fungus Leptosphaeria maculans (Mac) can be utilized to effectively inhibit excitable cells in C. elegans. Arch is the most powerful hyperpolarizer when illuminated with yellow or green light while the action spectrum of Mac is more blue-shifted, as analyzed by light-evoked behaviors and electrophysiology. This allows these tools to be combined in various ways with ChR2 to analyze different subsets of neurons within a circuit. We exemplify this by means of the polymodal aversive sensory ASH neurons, and the downstream command interneurons to which ASH neurons signal to trigger a reversal followed by a directional turn. Photostimulating ASH and subsequently inhibiting command interneurons using two-color illumination of different body segments, allows investigating temporal aspects of signaling downstream of ASH. PMID:22815873

  17. Nanoresolution radiology of neurons

    SciTech Connect

    Wu, H.R.; Chen, S.T.; Chu, Y.S.; Conley, R.; Bouet, N.; Chien, C.C.; Chen, H.H.; Lin, C.H.; Tung, H.T.; Chen, Y.S.; Margaritondo, G.; Je, J.H.; Hwu, Y.

    2013-04-08

    We report recent advances in hard-x-ray optics - including record spatial resolution - and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  18. Nanoresolution radiology of neurons

    SciTech Connect

    Wu, H. R.; Chen, S. T.; Chu, Y. S.; Conley, R.; Bouet, N.; Chien, C. C.; Chen, H. H.; Lin, C. H.; Tung, H. T.; Chen, Y. S.; Margaritondo, G.; Je, J. H.; Hwu, Y.

    2012-05-29

    We report recent advances in hard-x-ray optics—including record spatial resolution—and in staining techniques that enable synchrotron microradiology to produce neurobiology images of quality comparable to electron and visible microscopy. In addition, microradiology offers excellent penetration and effective three-dimensional detection as required for many neuron studies. Our tests include tomographic reconstruction based on projection image sets.

  19. Neuronal porosome lipidome

    PubMed Central

    Lewis, Kenneth T; Maddipati, Krishna R; Taatjes, Douglas J; Jena, Bhanu P

    2014-01-01

    Cup-shaped lipoprotein structures called porosomes are the universal secretory portals at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intravesicular contents. In neurons, porosomes measure ∼15 nm and are comprised of nearly 40 proteins, among them SNAREs, ion channels, the Gαo G-protein and several structural proteins. Earlier studies report the interaction of specific lipids and their influence on SNAREs, ion channels and G-protein function. Our own studies demonstrate the requirement of cholesterol for the maintenance of neuronal porosome integrity, and the influence of lipids on SNARE complex assembly. In this study, to further understand the role of lipids on porosome structure-function, the lipid composition of isolated neuronal porosome was determined using mass spectrometry. Using lipid-binding assays, the affinity of porosome-associated syntaxin-1A to various lipids was determined. Our mass spectrometry results demonstrate the presence of phosphatidylinositol phosphates (PIP's) and phosphatidic acid (PA) among other lipids, and the enriched presence of ceramide (Cer), lysophosphatidylinositol phosphates (LPIP) and diacylglycerol (DAG). Lipid binding assays demonstrate the binding of neuronal porosome to cardiolipin, and confirm its association with PIP's and PA. The ability of exogenous PA to alter protein–protein interaction and neurotransmitter release is further demonstrated from the study. PMID:25224862

  20. Dynamics of Perceived Exertion in Constant-Power Cycling: Time- and Workload-Dependent Thresholds

    ERIC Educational Resources Information Center

    Balagué, Natàlia; Hristovski, Robert; García, Sergi; Aguirre, Cecilia; Vázquez, Pablo; Razon, Selen; Tenenbaum, Gershon

    2015-01-01

    Purpose: 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. Method: 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,…

  1. Chronic exertional compartment syndrome of the superficial posterior compartment: Soleus syndrome

    PubMed Central

    Gross, Christopher E; Parekh, Bela J; Adams, Samuel B; Parekh, Selene G

    2015-01-01

    Chronic exertional compartment syndrome (CECS) represents the second most-common cause of exertional leg pain with incidence of 27-33%. CECS of the superficial posterior compartment, or soleus syndrome, is rare and has only been discussed briefly in the literature. We discuss the management of two patients with bilateral soleus syndrome or CECS of the superficial posterior compartment. PMID:26538766

  2. Chronic exertional compartment syndrome of the superficial posterior compartment: Soleus syndrome.

    PubMed

    Gross, Christopher E; Parekh, Bela J; Adams, Samuel B; Parekh, Selene G

    2015-01-01

    Chronic exertional compartment syndrome (CECS) represents the second most-common cause of exertional leg pain with incidence of 27-33%. CECS of the superficial posterior compartment, or soleus syndrome, is rare and has only been discussed briefly in the literature. We discuss the management of two patients with bilateral soleus syndrome or CECS of the superficial posterior compartment. PMID:26538766

  3. Neurotoxins as probes in the study of neuronal development.

    PubMed

    Berwald-Netter, Y; Couraud, F; Koulakoff, A; Martin-Moutot, N

    1982-01-01

    We have investigated the expression of surface membrane binding sites for tetanus toxin and alpha-scorpion toxin (AaHII) on cells of the in vivo developing mouse nervous system. There is a close temporal correlation in the pattern of emergence and accumulation of tetanus toxin binding cells (TBC) and that of post-mitotic neurons. In different nervous system areas, the fluctuations in relative TBC abundance reflect regional changes in the dynamics of neuronal subpopulations. The results indicate that the acquisition of membrane tetanus toxin binding sites may represent one of the earliest detectable characteristics of nascent neurons. The Na+ channel-associated scorpion toxin become detectable in fetal mouse brain two days after the appearance of TBC. Their density increases with fetal age without change in receptor properties. At all stages, scorpion toxin binds to a single class of noninteracting sites with a KD = 0.1 - 0.5 nM. The affinity of binding is voltage-dependent. Studies on brain cells and various cell lines grown in vitro suggest a selective association of the high affinity scorpion toxin receptors with neuronal phenotype. In culture, as in vivo, there is a time dependent increase in receptor density. These results indicate that both tetanus toxin and scorpion toxin can be used as qualitative markers of neuronal differentiation; moreover, estimates of the density of scorpion toxin binding sites provide a quantitative index of neuronal maturation. PMID:6281938

  4. Real-time visualization of neuronal activity during perception.

    PubMed

    Muto, Akira; Ohkura, Masamichi; Abe, Gembu; Nakai, Junichi; Kawakami, Koichi

    2013-02-18

    To understand how the brain perceives the external world, it is desirable to observe neuronal activity in the brain in real time during perception. The zebrafish is a suitable model animal for fluorescence imaging studies to visualize neuronal activity because its body is transparent through the embryonic and larval stages. Imaging studies have been carried out to monitor neuronal activity in the larval spinal cord and brain using Ca(2+) indicator dyes and DNA-encoded Ca(2+) indicators, such as Cameleon, GFP-aequorin, and GCaMPs. However, temporal and spatial resolution and sensitivity of these tools are still limited, and imaging of brain activity during perception of a natural object has not yet been demonstrated. Here we demonstrate visualization of neuronal activity in the optic tectum of larval zebrafish by genetically expressing the new version of GCaMP. First, we demonstrate Ca(2+) transients in the tectum evoked by a moving spot on a display and identify direction-selective neurons. Second, we show tectal activity during perception of a natural object, a swimming paramecium, revealing a functional visuotopic map. Finally, we image the tectal responses of a free-swimming larval fish to a paramecium and thereby correlate neuronal activity in the brain with prey capture behavior. PMID:23375894

  5. Ontogeny of Excitatory Spinal Neurons Processing Distinct Somatic Sensory Modalities

    PubMed Central

    Xu, Yi; Lopes, Claudia; Wende, Hagen; Guo, Zhen; Cheng, Leping; Birchmeier, Carmen

    2013-01-01

    Spatial and temporal cues govern the genesis of a diverse array of neurons located in the dorsal spinal cord, including dI1-dI6, dILA, and dILB subtypes, but their physiological functions are poorly understood. Here we generated a new line of conditional knock-out (CKO) mice, in which the homeobox gene Tlx3 was removed in dI5 and dILB cells. In these CKO mice, development of a subset of excitatory neurons located in laminae I and II was impaired, including itch-related GRPR-expressing neurons, PKCγ-expressing neurons, and neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1, and the gastrin-releasing peptide. These CKO mice displayed marked deficits in generating nocifensive motor behaviors evoked by a range of pain-related or itch-related stimuli. The mutants also failed to exhibit escape response evoked by dynamic mechanical stimuli but retained the ability to sense innocuous cooling and/or warm. Thus, our studies provide new insight into the ontogeny of spinal neurons processing distinct sensory modalities. PMID:24027274

  6. Epileptic Neuronal Networks: Methods of Identification and Clinical Relevance

    PubMed Central

    Stefan, Hermann; Lopes da Silva, Fernando H.

    2012-01-01

    The main objective of this paper is to examine evidence for the concept that epileptic activity should be envisaged in terms of functional connectivity and dynamics of neuronal networks. Basic concepts regarding structure and dynamics of neuronal networks are briefly described. Particular attention is given to approaches that are derived, or related, to the concept of causality, as formulated by Granger. Linear and non-linear methodologies aiming at characterizing the dynamics of neuronal networks applied to EEG/MEG and combined EEG/fMRI signals in epilepsy are critically reviewed. The relevance of functional dynamical analysis of neuronal networks with respect to clinical queries in focal cortical dysplasias, temporal lobe epilepsies, and “generalized” epilepsies is emphasized. In the light of the concepts of epileptic neuronal networks, and recent experimental findings, the dichotomic classification in focal and generalized epilepsy is re-evaluated. It is proposed that so-called “generalized epilepsies,” such as absence seizures, are actually fast spreading epilepsies, the onset of which can be tracked down to particular neuronal networks using appropriate network analysis. Finally new approaches to delineate epileptogenic networks are discussed. PMID:23532203

  7. Epigenomic Landscapes Reflect Neuronal Diversity.

    PubMed

    Henikoff, Steven

    2015-06-17

    Epigenomic profiling of complex tissues obscures regulatory elements that distinguish one cell type from another. In this issue of Neuron, Mo et al. (2015) apply cell-type-specific profiling to mouse neuronal subtypes and discover an unprecedented level of neuronal diversity. PMID:26087157

  8. The establishment of neuronal properties is controlled by Sox4 and Sox11

    PubMed Central

    Bergsland, Maria; Werme, Martin; Malewicz, Michal; Perlmann, Thomas; Muhr, Jonas

    2006-01-01

    The progression of neurogenesis relies on proneural basic helix–loop–helix (bHLH) transcription factors. These factors operate in undifferentiated neural stem cells and induce cell cycle exit and the initiation of a neurogenic program. However, the transient expression of proneural bHLH proteins in neural progenitors indicates that expression of neuronal traits must rely on previously unexplored mechanisms operating downstream from proneural bHLH proteins. Here we show that the HMG-box transcription factors Sox4 and Sox11 are of critical importance, downstream from proneural bHLH proteins, for the establishment of pan-neuronal protein expression. Examination of a neuronal gene promoter reveals that Sox4 and Sox11 exert their functions as transcriptional activators. Interestingly, the capacity of Sox4 and Sox11 to induce the expression of neuronal traits is independent of mechanisms regulating the exit of neural progenitors from the cell cycle. The transcriptional repressor protein REST/NRSF has been demonstrated to block neuronal gene expression in undifferentiated neural cells. We now show that REST/NRSF restricts the expression of Sox4 and Sox11, explaining how REST/NRSF can prevent precocious expression of neuronal proteins. Together, these findings demonstrate a central regulatory role of Sox4 and Sox11 during neuronal maturation and mechanistically separate cell cycle withdrawal from the establishment of neuronal properties. PMID:17182872

  9. Brainstem Reticulospinal Neurons are Targets for Corticotropin-Releasing Factor-Induced Locomotion in Roughskin Newts

    PubMed Central

    Hubbard, Catherine S.; Dolence, E. Kurt; Rose, James D.

    2009-01-01

    Stress-induced release or central administration of corticotropin-releasing factor (CRF) enhances locomotion in a wide range of vertebrates, including the roughskin newt, Taricha granulosa. Although CRF’s stimulatory actions on locomotor behavior are well established, the target neurons through which CRF exerts this effect remain unknown. To identify these target neurons, we utilized a fluorescent conjugate of CRF (CRF-TAMRA 1) to track this peptide’s internalization into reticulospinal and other neurons in the medullary reticular formation (MRF), a region critically involved in regulating locomotion. Epifluorescent and confocal microscopy revealed that CRF-TAMRA 1 was internalized by diverse MRF neurons, including reticulospinal neurons retrogradely labeled with Cascade Blue dextran. In addition, we immunohistochemically identified a distinct subset of serotonin-containing neurons, located throughout the medullary raphé, that also internalized the fluorescent CRF-TAMRA 1 conjugate. Chronic single-unit recordings obtained from microwire electrodes in behaving newts revealed that intracerebroventricular (icv) administration of CRF-TAMRA 1 increased medullary neuronal firing and that appearance of this firing was associated with, and strongly predictive of, episodes of CRF-induced locomotion. Furthermore, icv administered CRF-TAMRA 1 produced behavioral and neurophysiological effects identical to equimolar doses of unlabeled CRF. Collectively, these findings provide the first evidence that CRF directly targets reticulospinal and serotonergic neurons in the MRF and indicate that CRF may enhance locomotion via direct effects on the hindbrain, including the reticulospinal system. PMID:19968991

  10. Acute and Session Ratings of Perceived Exertion in a Physical Education Setting.

    PubMed

    Lagally, Kristen M; Walker-Smith, Kimberly; Henninger, Mary L; Williams, Skip M; Coleman, Margo

    2016-02-01

    A commonly stated rationale for examining the use of ratings of perceived exertion with youth is its potential value as an assessment of intensity in physical education settings. The purpose of this study was to examine the relation between ratings of perceived exertion and heart rate in a natural physical education setting. Sixth through eighth grade students performed cardiovascular and muscle endurance circuits and then recorded ratings and heart rate. It was hypothesized that, similar to laboratory studies, strong positive correlations would be seen between heart rate and ratings of perceived exertion, which would provide additional support for the use of ratings of perceived exertion in physical education. However, only low to moderate correlations were found. When data collection occurs in a natural physical education setting, there are challenges that may result in poor correlational results between variables such as heart rate and perceived exertion that demonstrate strong relationships when examined in laboratory settings. PMID:27420307

  11. Neuronal cell cycle: the neuron itself and its circumstances

    PubMed Central

    Frade, José M; Ovejero-Benito, María C

    2015-01-01

    Neurons are usually regarded as postmitotic cells that undergo apoptosis in response to cell cycle reactivation. Nevertheless, recent evidence indicates the existence of a defined developmental program that induces DNA replication in specific populations of neurons, which remain in a tetraploid state for the rest of their adult life. Similarly, de novo neuronal tetraploidization has also been described in the adult brain as an early hallmark of neurodegeneration. The aim of this review is to integrate these recent developments in the context of cell cycle regulation and apoptotic cell death in neurons. We conclude that a variety of mechanisms exists in neuronal cells for G1/S and G2/M checkpoint regulation. These mechanisms, which are connected with the apoptotic machinery, can be modulated by environmental signals and the neuronal phenotype itself, thus resulting in a variety of outcomes ranging from cell death at the G1/S checkpoint to full proliferation of differentiated neurons. PMID:25590687

  12. Methylene blue exerts a neuroprotective effect against traumatic brain injury by promoting autophagy and inhibiting microglial activation

    PubMed Central

    ZHAO, MINGFEI; LIANG, FENG; XU, HANGDI; YAN, WEI; ZHANG, JIANMIN

    2016-01-01

    Traumatic brain injury (TBI) leads to permanent neurological impairment, and methylene blue (MB) exerts central nervous system neuroprotective effects. However, only one previous study has investigated the effectiveness of MB in a controlled cortical impact injury model of TBI. In addition, the specific mechanisms underlying the effect of MB against TBI remain to be elucidated. Therefore, the present study investigated the neuroprotective effect of MB on TBI and the possible mechanisms involved. In a mouse model of TBI, the animals were randomly divided into sham, vehicle (normal saline) or MB groups. The treatment time-points were 24 and 72 h (acute phase of TBI), and 14 days (chronic phase of TBI) post-TBI. The brain water content (BWC), and levels of neuronal death, and autophagy were determined during the acute phase, and neurological deficit, injury volume and microglial activation were assessed at all time-points. The injured hemisphere BWC was significantly increased 24 h post-TBI, and this was attenuated following treatment with MB. There was a significantly higher number of surviving neurons in the MB group, compared with the Vehicle group at 24 and 72 h post-TBI. In the acute phase, the MB-treated animals exhibited significantly upregulated expression of Beclin 1 and increased LC3-II to LC3-I ratios, compared with the vehicle group, indicating an increased rate of autophagy. Neurological functional deficits, measured using the modified neurological severity score, were significantly lower in the acute phase in the MB-treated animals and cerebral lesion volumes in the MB-treated animals were significantly lower, compared with the other groups at all time-points. Microglia were activated 24 h after TBI, peaked at 72 h and persisted until 14 days after TBI. Although the number of Iba-1-positive cells in the vehicle and MB groups 24 h post-TBI were not significantly different, marked microglial inhibition was observed in the MB group 72 h and 14 days after

  13. Rich-Club Organization in Effective Connectivity among Cortical Neurons.

    PubMed

    Nigam, Sunny; Shimono, Masanori; Ito, Shinya; Yeh, Fang-Chin; Timme, Nicholas; Myroshnychenko, Maxym; Lapish, Christopher C; Tosi, Zachary; Hottowy, Pawel; Smith, Wesley C; Masmanidis, Sotiris C; Litke, Alan M; Sporns, Olaf; Beggs, John M

    2016-01-20

    The performance of complex networks, like the brain, depends on how effectively their elements communicate. Despite the importance of communication, it is virtually unknown how information is transferred in local cortical networks, consisting of hundreds of closely spaced neurons. To address this, it is important to record simultaneously from hundreds of neurons at a spacing that matches typical axonal connection distances, and at a temporal resolution that matches synaptic delays. We used a 512-electrode array (60 μm spacing) to record spontaneous activity at 20 kHz from up to 500 neurons simultaneously in slice cultures of mouse somatosensory cortex for 1 h at a time. We applied a previously validated version of transfer entropy to quantify information transfer. Similar to in vivo reports, we found an approximately lognormal distribution of firing rates. Pairwise information transfer strengths also were nearly lognormally distributed, similar to reports of synaptic strengths. Some neurons transferred and received much more information than others, which is consistent with previous predictions. Neurons with the highest outgoing and incoming information transfer were more strongly connected to each other than chance, thus forming a "rich club." We found similar results in networks recorded in vivo from rodent cortex, suggesting the generality of these findings. A rich-club structure has been found previously in large-scale human brain networks and is thought to facilitate communication between cortical regions. The discovery of a small, but information-rich, subset of neurons within cortical regions suggests that this population will play a vital role in communication, learning, and memory. Significance statement: Many studies have focused on communication networks between cortical brain regions. In contrast, very few studies have examined communication networks within a cortical region. This is the first study to combine such a large number of neurons (several

  14. Rich-Club Organization in Effective Connectivity among Cortical Neurons

    PubMed Central

    Shimono, Masanori; Ito, Shinya; Yeh, Fang-Chin; Timme, Nicholas; Myroshnychenko, Maxym; Lapish, Christopher C.; Tosi, Zachary; Hottowy, Pawel; Smith, Wesley C.; Masmanidis, Sotiris C.; Litke, Alan M.; Sporns, Olaf; Beggs, John M.

    2016-01-01

    The performance of complex networks, like the brain, depends on how effectively their elements communicate. Despite the importance of communication, it is virtually unknown how information is transferred in local cortical networks, consisting of hundreds of closely spaced neurons. To address this, it is important to record simultaneously from hundreds of neurons at a spacing that matches typical axonal connection distances, and at a temporal resolution that matches synaptic delays. We used a 512-electrode array (60 μm spacing) to record spontaneous activity at 20 kHz from up to 500 neurons simultaneously in slice cultures of mouse somatosensory cortex for 1 h at a time. We applied a previously validated version of transfer entropy to quantify information transfer. Similar to in vivo reports, we found an approximately lognormal distribution of firing rates. Pairwise information transfer strengths also were nearly lognormally distributed, similar to reports of synaptic strengths. Some neurons transferred and received much more information than others, which is consistent with previous predictions. Neurons with the highest outgoing and incoming information transfer were more strongly connected to each other than chance, thus forming a “rich club.” We found similar results in networks recorded in vivo from rodent cortex, suggesting the generality of these findings. A rich-club structure has been found previously in large-scale human brain networks and is thought to facilitate communication between cortical regions. The discovery of a small, but information-rich, subset of neurons within cortical regions suggests that this population will play a vital role in communication, learning, and memory. SIGNIFICANCE STATEMENT Many studies have focused on communication networks between cortical brain regions. In contrast, very few studies have examined communication networks within a cortical region. This is the first study to combine such a large number of neurons (several

  15. Temporal variability of spectro-temporal receptive fields in the anesthetized auditory cortex

    PubMed Central

    Meyer, Arne F.; Diepenbrock, Jan-Philipp; Ohl, Frank W.; Anemüller, Jörn

    2014-01-01

    Temporal variability of neuronal response characteristics during sensory stimulation is a ubiquitous phenomenon that may reflect processes such as stimulus-driven adaptation, top-down modulation or spontaneous fluctuations. It poses a challenge to functional characterization methods such as the receptive field, since these often assume stationarity. We propose a novel method for estimation of sensory neurons' receptive fields that extends the classic static linear receptive field model to the time-varying case. Here, the long-term estimate of the static receptive field serves as the mean of a probabilistic prior distribution from which the short-term temporally localized receptive field may deviate stochastically with time-varying standard deviation. The derived corresponding generalized linear model permits robust characterization of temporal variability in receptive field structure also for highly non-Gaussian stimulus ensembles. We computed and analyzed short-term auditory spectro-temporal receptive field (STRF) estimates with characteristic temporal resolution 5–30 s based on model simulations and responses from in total 60 single-unit recordings in anesthetized Mongolian gerbil auditory midbrain and cortex. Stimulation was performed with short (100 ms) overlapping frequency-modulated tones. Results demonstrate identification of time-varying STRFs, with obtained predictive model likelihoods exceeding those from baseline static STRF estimation. Quantitative characterization of STRF variability reveals a higher degree thereof in auditory cortex compared to midbrain. Cluster analysis indicates that significant deviations from the long-term static STRF are brief, but reliably estimated. We hypothesize that the observed variability more likely reflects spontaneous or state-dependent internal fluctuations that interact with stimulus-induced processing, rather than experimental or stimulus design. PMID:25566049

  16. Substantia nigra reticulata neurons during sleep-waking states: relation with ponto-geniculo-occipital waves.

    PubMed

    Datta, S; Curró Dossi, R; Paré, D; Oakson, G; Steriade, M

    1991-12-01

    We have previously hypothesized that the spike bursts of brainstem peribrachial (PB) neurons, leading to ponto-geniculo-occipital (PGO) waves in thalamocortical systems, are triggered by phasic hyperpolarizations of sufficient magnitude or by excitatory inputs reaching a steadily hyperpolarized membrane. We have proposed that the source of these hyperpolarizing actions are substantia nigra pars reticulata (SNr) cells that project to, and exert inhibitory effects upon, PB neurons. Here we tested this hypothesis by recording antidromically identified SNr-PB cells in chronically implanted, naturally sleeping cats. A subpopulation of SNr-PB cells exhibited tonically increased firing preceding by 70-200 ms the thalamic PGO wave. These data support the hypothesis that an enhancement in SNr-cells' discharges may lead to hyperpolarization of PB neurons, with the consequence of spike bursts in one class of PGO-related PB-thalamic neurons. PMID:1814553

  17. Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety.

    PubMed

    Wang, Guo-Qiang; Cen, Cheng; Li, Chong; Cao, Shuai; Wang, Ning; Zhou, Zheng; Liu, Xue-Mei; Xu, Yu; Tian, Na-Xi; Zhang, Ying; Wang, Jun; Wang, Li-Ping; Wang, Yun

    2015-01-01

    The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain. PMID:26179626

  18. Mesolimbic neuronal activity across behavioral states.

    PubMed

    Woodward, D J; Chang, J Y; Janak, P; Azarov, A; Anstrom, K

    1999-06-29

    A goal of neurophysiology of the mesolimbic system is to determine the activity patterns within the regions in the prefrontal cortex, ventral neostriatum, and amygdala that regulate behavioral patterns to seek rewards. A new technology has been introduced in which arrays of microwires are implanted in different brain regions while activity patterns of ensembles of neurons are recorded for long periods of time during freely moving behaviors. Multichannel instrumentation and software is used for data acquisition and analysis. An initial hypothesis was that neural signals would be encountered in the nucleus accumbens and associated regions specifically related to reward. However, an initial study of neural activity and behavioral patterns during a simple lever press for intravenous cocaine (1 mg/kg) revealed that phasic excitatory or inhibitory neural activity patterns often appear prior to the reward phase. Individual neurons throughout the mesolimbic system appear to code information specific to sensory and motor events, tones, or lever presses in the chain of tasks leading to all rewards so far studied. Different spatial temporal patterns also appear within the same neural populations, as reward is changed from injected cocaine to heroin, from ingested pure water to ethanol in water or sucrose. Overall, patterns of activity for each neuron are found to shift dynamically during the operant task as changes are made in the target reward. Significant shifts in activity of mesolimbic neurons that are unrelated to specific sensory-motor events also appear during complex sessions, such as during a bout of ethanol consumption to reach satiation or during progressive ratio tasks with increasing difficulty. An emerging hypothesis is that some candidate neural elements in the mesolimbic system code the anticipated reward, whereas others serve internal logic functions of motivation that mediate extinction or resumption of specific goal-directed behaviors. PMID:10415645

  19. Prototypic and Arkypallidal Neurons in the Dopamine-Intact External Globus Pallidus

    PubMed Central

    Abdi, Azzedine; Mallet, Nicolas; Mohamed, Foad Y.; Sharott, Andrew; Dodson, Paul D.; Nakamura, Kouichi C.; Suri, Sana; Avery, Sophie V.; Larvin, Joseph T.; Garas, Farid N.; Garas, Shady N.; Vinciati, Federica; Morin, Stéphanie; Bezard, Erwan

    2015-01-01

    Studies in dopamine-depleted rats indicate that the external globus pallidus (GPe) contains two main types of GABAergic projection cell; so-called “prototypic” and “arkypallidal” neurons. Here, we used correlative anatomical and electrophysiological approaches in rats to determine whether and how this dichotomous organization applies to the dopamine-intact GPe. Prototypic neurons coexpressed the transcription factors Nkx2-1 and Lhx6, comprised approximately two-thirds of all GPe neurons, and were the major GPe cell type innervating the subthalamic nucleus (STN). In contrast, arkypallidal neurons expressed the transcription factor FoxP2, constituted just over one-fourth of GPe neurons, and innervated the striatum but not STN. In anesthetized dopamine-intact rats, molecularly identified prototypic neurons fired at relatively high rates and with high regularity, regardless of brain state (slow-wave activity or spontaneous activation). On average, arkypallidal neurons fired at lower rates and regularities than prototypic neurons, and the two cell types could be further distinguished by the temporal coupling of their firing to ongoing cortical oscillations. Complementing the activity differences observed in vivo, the autonomous firing of identified arkypallidal neurons in vitro was slower and more variable than that of prototypic neurons, which tallied with arkypallidal neurons displaying lower amplitudes of a “persistent” sodium current important for such pacemaking. Arkypallidal neurons also exhibited weaker driven and rebound firing compared with prototypic neurons. In conclusion, our data support the concept that a dichotomous functional organization, as actioned by arkypallidal and prototypic neurons with specialized molecular, structural, and physiological properties, is fundamental to the operations of the dopamine-intact GPe. PMID:25926446

  20. Temporal patterning of neuroblasts controls Notch-mediated cell survival through regulation of Hid or Reaper

    PubMed Central

    Bertet, Claire; Li, Xin; Erclik, Ted; Cavey, Matthieu; Wells, Brent; Desplan, Claude

    2014-01-01

    Temporal patterning of neural progenitors is one of the core mechanisms generating neuronal diversity in the central nervous system. Here, we show that in the tips of the outer proliferation center (tOPC) of the developing Drosophila optic lobes, a unique temporal series of transcription factors not only governs the sequential production of distinct neuronal subtypes, but also controls the mode of progenitor division as well as the selective apoptosis of NotchOFF or NotchON neurons during binary cell fate decisions. Within a single lineage, intermediate precursors initially do not divide and generate only one neuron; subsequently, precursors divide but their NotchON progeny systematically die through Reaper activity whereas later, their NotchOFF progeny die through Hid activity. These mechanisms dictate how the tOPC produces neurons for three different optic ganglia. We conclude that temporal patterning generates neuronal diversity by specifying both the identity and survival/death of each unique neuronal subtype. PMID:25171415

  1. Stimulus features coded by single neurons of a macaque body category selective patch

    PubMed Central

    Popivanov, Ivo D.; Schyns, Philippe G.; Vogels, Rufin

    2016-01-01

    Body category-selective regions of the primate temporal cortex respond to images of bodies, but it is unclear which fragments of such images drive single neurons’ responses in these regions. Here we applied the Bubbles technique to the responses of single macaque middle superior temporal sulcus (midSTS) body patch neurons to reveal the image fragments the neurons respond to. We found that local image fragments such as extremities (limbs), curved boundaries, and parts of the torso drove the large majority of neurons. Bubbles revealed the whole body in only a few neurons. Neurons coded the features in a manner that was tolerant to translation and scale changes. Most image fragments were excitatory but for a few neurons both inhibitory and excitatory fragments (opponent coding) were present in the same image. The fragments we reveal here in the body patch with Bubbles differ from those suggested in previous studies of face-selective neurons in face patches. Together, our data indicate that the majority of body patch neurons respond to local image fragments that occur frequently, but not exclusively, in bodies, with a coding that is tolerant to translation and scale. Overall, the data suggest that the body category selectivity of the midSTS body patch depends more on the feature statistics of bodies (e.g., extensions occur more frequently in bodies) than on semantics (bodies as an abstract category). PMID:27071095

  2. Fast Neuronal Imaging using Objective Coupled Planar Illumination Microscopy

    NASA Astrophysics Data System (ADS)

    Tarantino, Walter

    Complex computations performed by the brain are produced by activities of neuronal populations. There is a large diversity in the functions of each individual neuron, and neuronal activities occur in the time scale of milliseconds. In order to gain a fundamental understanding of the neuronal populations, one has to measure activity of each neuron at high temporal resolution, while investigating enough neurons to encapsulate the neuronal diversity. Traditional neurotechniques such as electrophysiology and optical imaging are constrained by the number of neurons whose activities can be simultaneously measured or the speed of measuring such activities. We have developed a novel light-sheet based technique called Objective Coupled Planar Illumination (OCPI) microscopy which is capable of measuring simultaneous activities of thousands of neurons at high speeds. In this thesis I pursue the following two aims: · Improve OCPI microscopy by enhancing the spatial resolution deeper in tissue. Tissue inhomogeneity and refractive index mismatch at the surface of the tissue lead to optical aberrations. We have compensated for such aberrations by (1) miniaturizing the OCPI illumination optics, so as to enable more vertical imaging of the tissue, (2) correcting for the angular defocus caused by the refraction at the immersion fluid/tissue interface, and (3) applying adaptive optics to correct for higher order optical aberrations. The improvement in the depth at which one can image tissue will enable the measurement of activities of neuronal populations in cortical areas. · Measure the diversity in the expression pattern of VSNs responsive to sulfated steroids. Nodari et al. have identified sulfated steroids as a novel family of ligands which activate vomeronasal sensory neurons (VSNs). Due to the experimental constraints, it has not been possible to obtain a comprehensive understanding of the number, location and functional characteristics of the sulfated steroid responsive VSNs

  3. Phosphoinositide signaling in somatosensory neurons.

    PubMed

    Rohacs, Tibor

    2016-05-01

    Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels. PMID:26724974

  4. Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions

    PubMed Central

    Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V.; Field, Bianca; Deutch, Ariel Y.

    2015-01-01

    dopamine neurons are capable of glutamate cotransmission. With conditional expression of channelrhodopsin in dopamine neurons, we systematically explored dopamine neuron connections in the forebrain and identified regionally specific dopamine neuron excitatory connections. Establishing that only a subset of forebrain regions receive excitatory connections from dopamine neurons will help to determine the function of dopamine neuron glutamate cotransmission, which likely involves transmission of precise temporal signals and enhancement of the dynamic range of dopamine neuron signals. PMID:26658874

  5. Brain extracellular matrix retains connectivity in neuronal networks

    PubMed Central

    Bikbaev, Arthur; Frischknecht, Renato; Heine, Martin

    2015-01-01

    The formation and maintenance of connectivity are critically important for the processing and storage of information in neuronal networks. The brain extracellular matrix (ECM) appears during postnatal development and surrounds most neurons in the adult mammalian brain. Importantly, the removal of the ECM was shown to improve plasticity and post-traumatic recovery in the CNS, but little is known about the mechanisms. Here, we investigated the role of the ECM in the regulation of the network activity in dissociated hippocampal cultures grown on microelectrode arrays (MEAs). We found that enzymatic removal of the ECM in mature cultures led to transient enhancement of neuronal activity, but prevented disinhibition-induced hyperexcitability that was evident in age-matched control cultures with intact ECM. Furthermore, the ECM degradation followed by disinhibition strongly affected the network interaction so that it strongly resembled the juvenile pattern seen in naïve developing cultures. Taken together, our results demonstrate that the ECM plays an important role in retention of existing connectivity in mature neuronal networks that can be exerted through