Articles de revues : « Neuroni corticali »

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Masuda, Naoki, et Kazuyuki Aihara. « Spatiotemporal Spike Encoding of a Continuous External Signal ». Neural Computation 14, n^o 7 (1 juillet 2002) : 1599–628. http://dx.doi.org/10.1162/08997660260028638.

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Interspike intervals of spikes emitted from an integrator neuron model of sensory neurons can encode input information represented as a continuous signal from a deterministic system. If a real brain uses spike timing as a means of information processing, other neurons receiving spatiotemporal spikes from such sensory neurons must also be capable of treating information included in deterministic interspike intervals. In this article, we examine functions of neurons modeling cortical neurons receiving spatiotemporal spikes from many sensory neurons. We show that such neuron models can encode stimulus information passed from the sensory model neurons in the form of interspike intervals. Each sensory neuron connected to the cortical neuron contributes equally to the information collection by the cortical neuron. Although the incident spike train to the cortical neuron is a superimposition of spike trains from many sensory neurons, it need not be decomposed into spike trains according to the input neurons. These results are also preserved for generalizations of sensory neurons such as a small amount of leak, noise, inhomogeneity in firing rates, or biases introduced in the phase distributions.

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Zhou, Xiaoming, et Philip H. S. Jen. « Corticofugal Modulation of Multi-Parametric Auditory Selectivity in the Midbrain of the Big Brown Bat ». Journal of Neurophysiology 98, n^o 5 (novembre 2007) : 2509–16. http://dx.doi.org/10.1152/jn.00613.2007.

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Corticofugal modulation of sub-cortical auditory selectivity has been shown previously in mammals for frequency, amplitude, time, and direction domains in separate studies. As such, these studies do not show if multi-parametric corticofugal modulation can be mediated through the same sub-cortical neuron. Here we specifically studied corticofugal modulation of best frequency (BF), best amplitude (BA), and best azimuth (BAZ) at the same neuron in the inferior colliculus of the big brown bat, Eptesicus fuscus, using focal electrical stimulation in the auditory cortex. Among 53 corticofugally inhibited collicular neurons examined, cortical electrical stimulation produced a shift of all three measurements (i.e., BF, BA, and BAZ) toward the value of stimulated cortical neuron in 13 (24.5%) neurons, two measurements (i.e., BF and BAZ or BA and BAZ) in 19 (36%) neurons, and one measurement in 16 (30%) neurons. Cortical electrical stimulation did not shift any of these measurements in the remaining five (9.5%) neurons. Corticofugally induced collicular BF shift was symmetrical, whereas the shift in collicular BA or BAZ was asymmetrical. The amount of shift in each measurement was significantly correlated with each measurement difference between recorded collicular and stimulated cortical neurons. However, shifts of three measurements were not correlated with each other. Furthermore, average measurement difference between collicular and cortical neurons was larger for collicular neurons with measurement shifts than for those without shifts. These data indicate that multi-parametric corticofugal modulation can be mediated through the same subcortical neuron based on the difference in auditory selectivity between subcortical and cortical neurons.

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Wright, Nathaniel C., Mahmood S. Hoseini, Tansel Baran Yasar et Ralf Wessel. « Coupling of synaptic inputs to local cortical activity differs among neurons and adapts after stimulus onset ». Journal of Neurophysiology 118, n^o 6 (1 décembre 2017) : 3345–59. http://dx.doi.org/10.1152/jn.00398.2017.

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Cortical activity contributes significantly to the high variability of sensory responses of interconnected pyramidal neurons, which has crucial implications for sensory coding. Yet, largely because of technical limitations of in vivo intracellular recordings, the coupling of a pyramidal neuron’s synaptic inputs to the local cortical activity has evaded full understanding. Here we obtained excitatory synaptic conductance ( g) measurements from putative pyramidal neurons and local field potential (LFP) recordings from adjacent cortical circuits during visual processing in the turtle whole brain ex vivo preparation. We found a range of g-LFP coupling across neurons. Importantly, for a given neuron, g-LFP coupling increased at stimulus onset and then relaxed toward intermediate values during continued visual stimulation. A model network with clustered connectivity and synaptic depression reproduced both the diversity and the dynamics of g-LFP coupling. In conclusion, these results establish a rich dependence of single-neuron responses on anatomical, synaptic, and emergent network properties. NEW & NOTEWORTHY Cortical neurons are strongly influenced by the networks in which they are embedded. To understand sensory processing, we must identify the nature of this influence and its underlying mechanisms. Here we investigate synaptic inputs to cortical neurons, and the nearby local field potential, during visual processing. We find a range of neuron-to-network coupling across cortical neurons. This coupling is dynamically modulated during visual processing via biophysical and emergent network properties.

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Alloway, K. D., M. J. Johnson et M. B. Wallace. « Thalamocortical interactions in the somatosensory system : interpretations of latency and cross-correlation analyses ». Journal of Neurophysiology 70, n^o 3 (1 septembre 1993) : 892–908. http://dx.doi.org/10.1152/jn.1993.70.3.892.

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1. Isolated extracellular neuronal responses to cutaneous stimulation were simultaneously recorded from corresponding peripheral representations in the ventrobasal nucleus and primary somatosensory cortex of intact, halothane-anesthetized rats. Thalamic and cortical neurons representing hairy skin on the forelimb were activated by hair movements produced by a series of 50 or 100 discrete air jets. A corresponding set of neurons representing the glabrous pads of the hind paw were activated by a similar number of punctate mechanical displacements. 2. Cortical electrode penetrations were histologically reconstructed, and 118 neurons in the glabrous skin representation exhibited cutaneous responses that were categorized into supragranular, granular, or infragranular groups according to their laminar position. Minimum latencies of cortical neurons responding to glabrous skin displacement were analyzed, and significant differences were found in the distribution of minimum latencies for the different cortical layers. Mean values for minimum latencies in the infragranular and granular layers were 15.8 and 16.3 ms, respectively, whereas supragranular neurons were characterized by minimum latencies having a mean of 20 ms. The differences between these groups suggests that stimulus-induced afferent activity reaches infragranular and granular layers before contacting supragranular neurons. Average latencies were also calculated on responses occurring during the 1st 20 trials, but the cortical distributions of these values overlapped considerably, and differences between the laminar groups were not statistically significant. 3. In several recording sites, two cortical neurons were recorded simultaneously, and the response latencies of these matched pairs were often substantially different despite the similarity in laminar position. This result indicates that laminar location is not the only determinant of response latency and that serially organized circuits are distributed within, as well as between, cortical layers. 4. From a sample of 302 neurons exhibiting cutaneous responses within histologically identified regions of thalamus or cortex, a set of 143 pairs of neurons recorded simultaneously from both regions was available for cross-correlation analysis. Significant thalamocortical interactions were found in 38 neurons pairs. Analysis of these significant interactions revealed that thalamocortical connection strength, as measured by neuronal efficacy, was two to four times larger for neuron pairs having the cortical cell in granular layer IV than for neuron pairs having an extragranular layer cortical neuron. There was no difference in thalamocortical connection strength between neuron pairs containing supra- or infragranular cortical neurons. 5. Summed peristimulus time histograms revealed stimulus-locked inhibition of spontaneous activity in 4% (8/195) or cortical and 18% (20/107) of thalamic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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Yamamoto, T., N. Yuyama, T. Kato et Y. Kawamura. « Gustatory responses of cortical neurons in rats. II. Information processing of taste quality ». Journal of Neurophysiology 53, n^o 6 (1 juin 1985) : 1356–69. http://dx.doi.org/10.1152/jn.1985.53.6.1356.

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The present report was designed to investigate neural coding of taste information in the cerebral cortical taste area of rats. The magnitude and/or type (excitatory, inhibitory, or no-response) of responses of 111 cortical neurons evoked by single concentrations of the four basic taste stimuli (sucrose, NaCl, HCl, and quinine HCl) were subjected to four types of analyses in the context of the four proposed hypotheses of taste-quality coding: across-neuron response-pattern, labeled-line, matrix-pattern, and across-region response-pattern notions (88 histologically located neurons). An across-neuron response-pattern notion assumes that taste quality is coded by differential magnitudes of response across many neurons. This theory utilizes across-neuron correlation coefficients as a metric for the evaluation of taste quality coding. Across-neuron correlations between magnitudes of responses to any pairs of the four basic taste stimuli across 111 cortical neurons were very high and were similar. However, calculations made with net responses (spontaneous rate subtracted) resulted in less positive correlations but still similar values among the various pairs of taste stimuli. This finding suggests that across-neuron response patterns of cortical neurons become less discriminating among taste qualities compared with those of the lower-order neurons. A labeled-line notion assumes that there are identifiable groups of neurons and that taste quality is coded by activity in these particular sets of neurons. Some investigators have classified taste-responsive neurons into best-stimulus categories, depending on their best sensitivity to any one of the four basic stimuli, such as sucrose-best, NaCl-best, HCl-best, and quinine-best neurons; they have suggested that taste can be classified along four qualitative dimensions that correspond to these four neuron types (i.e., four labeled lines). The present study shows that responsiveness of each of the four best-stimulus neurons had similar profiles between peripheral and cortical levels. That is, when the stimuli were arranged along the abscissa in the order of sucrose, NaCl, HCl, and quinine, there is a peak response in one place, and the responses decreased gradually from the peak. However, such response characteristics do not favor the labeled-line theory, since they can be explained in the context of the across-neuron pattern theory. A matrix-pattern notion assumes that taste quality is coded by a spatially arranged matrix pattern of activated neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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Shinomoto, Shigeru, Keisetsu Shima et Jun Tanji. « Differences in Spiking Patterns Among Cortical Neurons ». Neural Computation 15, n^o 12 (1 décembre 2003) : 2823–42. http://dx.doi.org/10.1162/089976603322518759.

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Spike sequences recorded from four cortical areas of an awake behaving monkey were examined to explore characteristics that vary among neurons. We found that a measure of the local variation of interspike intervals, LV, is nearly the same for every spike sequence for any given neuron, while it varies significantly among neurons. The distributions of LV values for neuron ensembles in three of the four areas were found to be distinctly bimodal. Two groups of neurons classified according to the spiking irregularity exhibit different responses to the same stimulus. This suggests that neurons in each area can be classified into different groups possessing unique spiking statistics and corresponding functional properties.

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Unda, Brianna K., Vickie Kwan et Karun K. Singh. « Neuregulin-1 Regulates Cortical Inhibitory Neuron Dendrite and Synapse Growth through DISC1 ». Neural Plasticity 2016 (2016) : 1–15. http://dx.doi.org/10.1155/2016/7694385.

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Cortical inhibitory neurons play crucial roles in regulating excitatory synaptic networks and cognitive function and aberrant development of these cells have been linked to neurodevelopmental disorders. The secreted neurotrophic factor Neuregulin-1 (NRG1) and its receptor ErbB4 are established regulators of inhibitory neuron connectivity, but the developmental signalling mechanisms regulating this process remain poorly understood. Here, we provide evidence that NRG1-ErbB4 signalling functions through the multifunctional scaffold protein, Disrupted in Schizophrenia 1 (DISC1), to regulate the development of cortical inhibitory interneuron dendrite and synaptic growth. We found that NRG1 increases inhibitory neuron dendrite complexity and glutamatergic synapse formation onto inhibitory neurons and that this effect is blocked by expression of a dominant negative DISC1 mutant, or DISC1 knockdown. We also discovered that NRG1 treatment increases DISC1 expression and its localization to glutamatergic synapses being made onto cortical inhibitory neurons. Mechanistically, we determined that DISC1 binds ErbB4 within cortical inhibitory neurons. Collectively, these data suggest that a NRG1-ErbB4-DISC1 signalling pathway regulates the development of cortical inhibitory neuron dendrite and synaptic growth. Given that NRG1, ErbB4, and DISC1 are schizophrenia-linked genes, these findings shed light on how independent risk factors may signal in a common developmental pathway that contributes to neural connectivity defects and disease pathogenesis.

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Doll, C. J., P. W. Hochachka et P. B. Reiner. « Effects of anoxia and metabolic arrest on turtle and rat cortical neurons ». American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 260, n^o 4 (1 avril 1991) : R747—R755. http://dx.doi.org/10.1152/ajpregu.1991.260.4.r747.

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The responses of turtle and rat cortical pyramidal neurons to various pharmacological treatments were measured using intracellular recordings. Turtle neurons survived both anoxia and pharmacological anoxia for 180 min with no noticeable effect. Rat pyramidal neurons responded with a loss in membrane resistance, followed by a transient hyperpolarization, and a subsequent depolarization to a zero membrane potential (41.3 +/- 6.5 min, anoxia; 25.8 +/- 12.6 min, pharmacological anoxia). Metabolic arrest caused a rapid loss in membrane resistance, transient hyperpolarization, and a rapid depolarization in both turtle (4.6 +/- 1.1 min) and rat (3.1 +/- 0.5 min) neurons. Iodoacetate alone had a similar effect on the rat as metabolic arrest (6.5 +/- 0.8 min), but the turtle exhibited more prolonged survival (53.5 +/- 4.6 min). Ouabain caused a rapid depolarization in the rat cortical neuron (8.6 +/- 1.1 min), but no initial loss in membrane resistance or a hyperpolarization. These results demonstrate that the turtle neuron, which survives anoxia, is no better at surviving total metabolic inhibition than the rat neuron. In addition, anoxia takes 13 times longer to depolarize a rat cortical neuron than metabolic arrest, and neither of these treatments is totally mimicked by ouabain alone.

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Collins, Christine E., Emily C. Turner, Eva Kille Sawyer, Jamie L. Reed, Nicole A. Young, David K. Flaherty et Jon H. Kaas. « Cortical cell and neuron density estimates in one chimpanzee hemisphere ». Proceedings of the National Academy of Sciences 113, n^o 3 (4 janvier 2016) : 740–45. http://dx.doi.org/10.1073/pnas.1524208113.

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The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm2 of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

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Murray, Peter D., et Asaf Keller. « Somatosensory response properties of excitatory and inhibitory neurons in rat motor cortex ». Journal of Neurophysiology 106, n^o 3 (septembre 2011) : 1355–62. http://dx.doi.org/10.1152/jn.01089.2010.

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In sensory cortical networks, peripheral inputs differentially activate excitatory and inhibitory neurons. Inhibitory neurons typically have larger responses and broader receptive field tuning compared with excitatory neurons. These differences are thought to underlie the powerful feedforward inhibition that occurs in response to sensory input. In the motor cortex, as in the somatosensory cortex, cutaneous and proprioceptive somatosensory inputs, generated before and during movement, strongly and dynamically modulate the activity of motor neurons involved in a movement and ultimately shape cortical command. Human studies suggest that somatosensory inputs modulate motor cortical activity in a center excitation, surround inhibition manner such that input from the activated muscle excites motor cortical neurons that project to it, whereas somatosensory input from nearby, nonactivated muscles inhibit these neurons. A key prediction of this hypothesis is that inhibitory and excitatory motor cortical neurons respond differently to somatosensory inputs. We tested this prediction with the use of multisite extracellular recordings in anesthetized rats. We found that fast-spiking (presumably inhibitory) neurons respond to tactile and proprioceptive inputs at shorter latencies and larger response magnitudes compared with regular-spiking (presumably excitatory) neurons. In contrast, we found no differences in the receptive field size of these neuronal populations. Strikingly, all fast-spiking neuron pairs analyzed with cross-correlation analysis displayed common excitation, which was significantly more prevalent than common excitation for regular-spiking neuron pairs. These findings suggest that somatosensory inputs preferentially evoke feedforward inhibition in the motor cortex. We suggest that this provides a mechanism for dynamic selection of motor cortical modules during voluntary movements.

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Lytton, William W., Diego Contreras, Alain Destexhe et Mircea Steriade. « Dynamic Interactions Determine Partial Thalamic Quiescence in a Computer Network Model of Spike-and-Wave Seizures ». Journal of Neurophysiology 77, n^o 4 (1 avril 1997) : 1679–96. http://dx.doi.org/10.1152/jn.1997.77.4.1679.

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Lytton, William W., Diego Contreras, Alain Destexhe, and Mircea Steriade. Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures. J. Neurophysiol. 77: 1679–1696, 1997. In vivo intracellular recording from cat thalamus and cortex was performed during spontaneous spike-wave seizures characterized by synchronously firing cortical neurons correlated with the electroencephalogram. During these seizures, thalamic reticular (RE) neurons discharged with long spike bursts riding on a depolarization, whereas thalamocortical (TC) neurons were either entrained into the seizures (40%) or were quiescent (60%). During quiescence, TC neurons showed phasic inhibitory postsynaptic potentials (IPSPs) that coincided with paroxysmal depolarizing shifts in the simultaneously recorded cortical neuron. Computer simulations of a reciprocally connected TC-RE pair showed two major modes of TC-RE interaction. In one mode, a mutual oscillation involved direct TC neuron excitation of the RE neuron leading to a burst that fed back an IPSP into the TC neuron, producing a low-threshold spike. In the other, quiescent mode, the TC neuron was subject to stronger coalescing IPSPs. Simulated cortical stimulation could trigger a transition between the two modes. This transition could go in either direction and was dependent on the precise timing of the input. The transition did not always follow the stimulation immediately. A larger, multicolumnar simulation was set up to assess the role of the TC-RE pair in the context of extensive divergence and convergence. The amount of TC neuron spiking generally correlated with the strength of total inhibitory input, but large variations in the amount of spiking could be seen. Evidence for mutual oscillation could be demonstrated by comparing TC neuron firing with that in reciprocally connected RE neurons. An additional mechanism for TC neuron quiescence was assessed with the use of a cooperative model of γ-aminobutyric acid-B (GABAB)-mediated responses. With this model, RE neurons receiving repeated strong excitatory input produced TC neuron quiescence due to burst-duration-associated augmentation of GABAB current. We predict the existence of spatial inhomogeneity in apparently generalized spike-wave seizures, involving a center-surround pattern. In the center, intense cortical and RE neuron activity would be associated with TC neuron quiescence. In the surround, less intense hyperpolarization of TC neurons would allow low-threshold spikes to occur. This surround, an “epileptic penumbra,” would be the forefront of the expanding epileptic wave during the process of initial seizure generalization. Therapeutically, we would then predict that agents that reduce TC neuron activity would have a greater effect on seizure onset than on ongoing spike-wave seizures or other thalamic oscillations.

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Suri, Roland E., et Wolfram Schultz. « Temporal Difference Model Reproduces Anticipatory Neural Activity ». Neural Computation 13, n^o 4 (1 avril 2001) : 841–62. http://dx.doi.org/10.1162/089976601300014376.

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Anticipatory neural activity preceding behaviorally important events has been reported in cortex, striatum, and midbrain dopamine neurons. Whereas dopamine neurons are phasically activated by reward-predictive stimuli, anticipatory activity of cortical and striatal neurons is increased during delay periods before important events. Characteristics of dopa-mine neuron activity resemble those of the prediction error signal of the temporal difference (TD) model of Pavlovian learning (Sutton & Barto, 1990). This study demonstrates that the prediction signal of the TD model reproduces characteristics of cortical and striatal anticipatory neural activity. This finding suggests that tonic anticipatory activities may reflect prediction signals that are involved in the processing of dopamine neuron activity.

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Turner, Emily C., Nicole A. Young, Jamie L. Reed, Christine E. Collins, David K. Flaherty, Mariana Gabi et Jon H. Kaas. « Distributions of Cells and Neurons across the Cortical Sheet in Old World Macaques ». Brain, Behavior and Evolution 88, n^o 1 (2016) : 1–13. http://dx.doi.org/10.1159/000446762.

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According to previous research, cell and neuron densities vary across neocortex in a similar manner across primate taxa. Here, we provide a more extensive examination of this effect in macaque monkeys. We separated neocortex from the underlying white matter in 4 macaque monkey hemispheres (1 Macaca nemestrina, 2 Macaca radiata, and 1 Macaca mulatta), manually flattened the neocortex, and divided it into smaller tissue pieces for analysis. The number of cells and neurons were determined for each piece across the cortical sheet using flow cytometry. Primary visual cortex had the most densely packed neurons and primary motor cortex had the least densely packed neurons. With respect to differences in brain size between cases, there was little variability in the total cell and neuron numbers within specific areas, and overall trends were similar to what has been previously described in Old World baboons and other primates. The average hemispheric total cell number per hemisphere ranged from 2.9 to 3.7 billion, while the average total neuron number ranged from 1.3 to 1.7 billion neurons. The visual cortex neuron densities were predictably higher, ranging from 18.2 to 34.7 million neurons/cm2 in macaques, in comparison to a range of 9.3-17.7 million neurons/cm2 across cortex as a whole. The results support other evidence that neuron surface densities vary across the cortical sheet in a predictable pattern within and across primate taxa.

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Reyes, Laura D., Tessa Harland, Roger L. Reep, Chet C. Sherwood et Bob Jacobs. « Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris) ». Brain, Behavior and Evolution 87, n^o 2 (2016) : 105–16. http://dx.doi.org/10.1159/000445495.

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

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Shoykhet, Michael, et Daniel J. Simons. « Development of Thalamocortical Response Transformations in the Rat Whisker-Barrel System ». Journal of Neurophysiology 99, n^o 1 (janvier 2008) : 356–66. http://dx.doi.org/10.1152/jn.01063.2007.

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Extracellular single-unit recordings were used to characterize responses of thalamic barreloid and cortical barrel neurons to controlled whisker deflections in 2, 3-, and 4-wk-old and adult rats in vivo under fentanyl analgesia. Results indicate that response properties of thalamic and cortical neurons diverge during development. Responses to deflection onsets and offsets among thalamic neurons mature in parallel, whereas among cortical neurons responses to deflection offsets become disproportionately smaller with age. Thalamic neuron receptive fields become more multiwhisker, whereas those of cortical neurons become more single-whisker. Thalamic neurons develop a higher degree of angular selectivity, whereas that of cortical neurons remains constant. In the temporal domain, response latencies decrease both in thalamic and cortical neurons, but the maturation time-course differs between the two populations. Response latencies of thalamic cells decrease primarily between 2 and 3 wk of life, whereas response latencies of cortical neurons decrease in two distinct steps—the first between 2 and 3 wk of life and the second between the fourth postnatal week and adulthood. Although the first step likely reflects similar subcortical changes, the second phase likely corresponds to developmental myelination of thalamocortical fibers. Divergent development of thalamic and cortical response properties indicates that thalamocortical circuits in the whisker-to-barrel pathway undergo protracted maturation after 2 wk of life and provides a potential substrate for experience-dependent plasticity during this time.

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Shinomoto, Shigeru, Youichi Miyazaki, Hiroshi Tamura et Ichiro Fujita. « Regional and Laminar Differences in In Vivo Firing Patterns of Primate Cortical Neurons ». Journal of Neurophysiology 94, n^o 1 (juillet 2005) : 567–75. http://dx.doi.org/10.1152/jn.00896.2004.

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The firing rates of cortical neurons change in time; yet, some aspects of their in vivo firing characteristics remain unchanged and are specific to individual neurons. A recent study has shown that neurons in the monkey medial motor areas can be grouped into 2 firing types, “likely random” and “quasi-regular,” according to a measure of local variation of interspike intervals. In the present study, we extended this analysis to area TE of the inferior temporal cortex and addressed whether this classification applies generally to different cortical areas and whether different types of neurons show different laminar distribution. We found that area TE did consist of 2 groups of neurons with different firing characteristics, one similar to the “likely random” type in the medial motor cortical areas, and the other exhibiting a “clumpy-bursty” firing pattern unique to TE. The quasi-regular type was rarely observed in area TE. The likely random firing type of neuron was more frequently found in layers V–VI than in layers II–III, whereas the opposite was true for the clumpy-bursty firing type. These results show that neocortical areas consist of heterogeneous neurons that differ from one area to another in their basic firing characteristics. Moreover, we show that spike trains obtained from a single cortical neuron can provide a clue that helps to identify its layer localization.

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Karnani, Mahesh M., et Jesse Jackson. « Interneuron Cooperativity in Cortical Circuits ». Neuroscientist 24, n^o 4 (27 septembre 2017) : 329–41. http://dx.doi.org/10.1177/1073858417733719.

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Neocortical neurons tend to be coactive in groups called ensembles. However, sometimes, individual neurons also spike alone, independent of the ensemble. What processes regulate the transition between individual and cooperative action? Inspired by classical work in biochemistry, we apply the concept of neuronal cooperativity to explore this question. With a focus on neocortical inhibitory interneurons, we offer a working definition of neuronal cooperativity, review its recorded incidences and proposed mechanisms, and describe experimental approaches that will demonstrate and further describe this action. We suggest that cooperativity of “neuron teams” is manifested in vivo through their coactivity, as well as via the action of individual “soloist neurons” in the low end of the sigmoidal cooperativity curve. Finally, we explore the evidence for and implications of individual and team action of neurons.

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Johnson, M. J., et K. D. Alloway. « Cross-correlation analysis reveals laminar differences in thalamocortical interactions in the somatosensory system ». Journal of Neurophysiology 75, n^o 4 (1 avril 1996) : 1444–57. http://dx.doi.org/10.1152/jn.1996.75.4.1444.

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1. Spontaneous and stimulus-induced activity were recorded from corresponding somatotopic representations in the ventroposterolateral nucleus (VPL) of the thalamus and primary somatosensory (SI) cortex of intact, halothane-anesthetized cats. Thalamic and cortical neurons with overlapping receptive fields on the hairy skin of the forelimb were excited by a series of interleaved air jets aimed at multiple skin sites. 2. The laminar locations of 68% (240 of 355) of the neurons recorded in SI cortex were histologically reconstructed and responses of these 240 SI neurons were analyzed with respect to responses recorded from 118 thalamic neurons. Maximum responsiveness during the initial onset (1st 100 ms) of air jet stimulation was similar for neurons distributed throughout all layers of SI cortex (2-4 spikes per stimulus) and did not differ significantly from VPL responses. During the subsequent plateau phase of the stimulus, VPL neurons discharged at a mean rate of 19.0 spikes/ s and neurons in cortical layers II, IIIa, IIIb, and IV discharged at similar rates. Mean responsiveness during the plateau phase of the stimulus was significantly reduced among neurons in cortical layers V and VI and only averaged 7.1 and 3.9 spikes/s, respectively. 3. Responses recorded simultaneously from pairs of thalamic and cortical neurons were analyzed with cross-correlation analysis to determine differences in the incidence and strength of neuronal interactions as a function of cortical layer. Among 421 thalamocortical neuron pairs displaying stimulus-induced responses, 68 neuron pairs exhibited significant interactions during air jet stimulation. A laminar analysis revealed that 28% (45 of 163) of the neurons in the middle cortical layers displayed significant interactions with thalamic neurons, whereas only 14% (13 of 92) of superficial layer neurons and 6% (10 of 166) of deep layer neurons were synchronized with thalamic activity during air jet stimulation. When thalamocortical efficacy for different layers of cortex was plotted as a cumulative frequency distribution, the strongest interactions in the middle cortical layers were twice as strong as interactions involving the superficial or deep cortical layers. 4. More than 70% of stimulus-induced interactions involved thalamic discharges followed by subsequent cortical discharges and the majority of these interactions involved interspike intervals of < or = 3 ms. Nearly 75% (27 of 37) of interactions in the thalamocortical direction that involved cortical neurons in layers IIIb and IV transpired within a 3-ms interspike interval. For interactions with superficial or deep cortical layers, the proportion of thalamocortical interactions transpiring within 3 ms was only 58% (7 of 12) and 33% (2 of 6), respectively. 5. Cross-correlation analysis of spontaneous activity indicated that 124 pairs of thalamic and cortical neurons displayed synchronous activity in the absence of sensory stimulation. A laminar analysis indicated that similar proportions of cortical neurons in each layer were synchronized with thalamic activity in the absence of cutaneous stimulation. Thus 27% (44 of 163) of middle layer neurons, 30% (28 of 92) of superficial layer neurons, and 31% (51 of 166) of deep layer neurons displayed spontaneous interactions with thalamic neurons. The temporal pattern of spontaneous activity was examined with autocorrelation analysis to determine whether neuronal oscillations were essential for coordinating thalamic and cortical activity in the absence of peripheral stimulation. Only 18.5% (23 of 124) of spontaneous interactions between thalamic and cortical neurons were associated with periodic activity, which suggests that thalamocortical synchronization occurs before the constituent neurons begin to oscillate. 6. The influence of sensory stimulation on spontaneous interactions was examined in 31 pairs of thalamic and cortical neurons that exhibited interactions during prestimulus and stimulus in

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Madsen, Jesper Guldsmed, Jakob Appel Østergaard, Henning Andersen et Michael Pedersen. « Attenuation of Cortically Evoked Motor-Neuron Potential in Streptozotocin-Induced Diabetic Rats : A Study about the Effect of Diabetes upon Cortical-Initiated Movement ». BioMed Research International 2020 (26 février 2020) : 1–5. http://dx.doi.org/10.1155/2020/1942534.

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Aims/Hypothesis. The complications affecting the peripheral nervous system, associated with diabetes mellitus, have been the focus of considerable research. Comparably less research has focused upon the effect of diabetes upon the central nervous system. In this study, we investigate the effect of diabetes upon motor-neuron potentials evoked in the motor cortex of streptozotocin diabetic rats. Methods. In this study, we investigated the cortical-evoked motor-neuron potentials in streptozotocin-induced diabetic rats. Cortical potentials were evoked using direct current stimulation to the motor cortex, and the resulting evoked potentials were recorded in the sciatic nerve. As voluntary movement consists of repeated activation of muscles, repeated stimulation trials were used to determine the effect of diabetes upon the animals’ ability to recuperate between stimulations. Results. Our findings showed that diabetes severely decreased the amplitude of cortical-evoked potentials and compromised the recuperation of motor neurons between activation. Conclusion/Interpretation. The reduced amplitude and weakened recuperation of diabetic motor neurons potentially may contribute to impaired transmission in motor pathways and thereby motor dysfunction.

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Yu, Huan-Ling, Li Li, Xiao-Hong Zhang, Li Xiang, Jie Zhang, Jin-Fang Feng et Rong Xiao. « Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by β-amyloid 31-35 ». British Journal of Nutrition 102, n^o 5 (14 septembre 2009) : 655–62. http://dx.doi.org/10.1017/s0007114509243042.

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Genistein and folic acid have been reported respectively to protect against the development of cognitive dysfunction; however, the underlying mechanism(s) for this protection remain unknown. In this report, the mechanism(s) contributing to the neuroprotective effects of genistein and folic acid were explored using rat cortical neuron cultures. We found that genistein and folic acid, both separately and collaboratively, increased cell viability and mitochondrial membrane potential in β-amyloid (Aβ) 31-35-treated neurons. Furthermore, reduced percentage of comet cells and shortened tail length were observed in the neurons treated with genistein or folic acid. A more significant reduction in tail length of the comet neurons was observed in the co-administered neurons. RT-PCR analysis of the cultured cortical neurons showed down-regulated expression of p53, bax and caspase-3, but up-regulated expression of bcl-2 in the three neuroprotective treatment groups compared with neurons from the Aβ31-35 solo-treated group. In a nuclear dyeing experiment using Hoechst 33342, we found that both genistein and folic acid prevent neuronal apoptosis. Collectively, these findings suggest that the mechanism underlying the neuroprotection of genistein and folic acid singly or in combination observed in cultured cortical neuron studies might be related to their anti-apoptotic properties.

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Tsubomoto, Makoto, Rika Kawabata, Xiaonan Zhu, Yoshio Minabe, Kehui Chen, David A. Lewis et Takanori Hashimoto. « Expression of Transcripts Selective for GABA Neuron Subpopulations across the Cortical Visuospatial Working Memory Network in the Healthy State and Schizophrenia ». Cerebral Cortex 29, n^o 8 (24 septembre 2018) : 3540–50. http://dx.doi.org/10.1093/cercor/bhy227.

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Abstract Visuospatial working memory (WM), which is impaired in schizophrenia, depends on a distributed network including visual, posterior parietal, and dorsolateral prefrontal cortical regions. Within each region, information processing is differentially regulated by subsets of γ-aminobutyric acid (GABA) neurons that express parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP). In schizophrenia, WM impairments have been associated with alterations of PV and SST neurons in the dorsolateral prefrontal cortex. Here, we quantified transcripts selectively expressed in GABA neuron subsets across four cortical regions in the WM network from comparison and schizophrenia subjects. In comparison subjects, PV mRNA levels declined and SST mRNA levels increased from posterior to anterior regions, whereas VIP mRNA levels were comparable across regions except for the primary visual cortex (V1). In schizophrenia subjects, each transcript in PV and SST neurons exhibited similar alterations across all regions, whereas transcripts in VIP neurons were unaltered in any region except for V1. These findings suggest that the contribution of each GABA neuron subset to inhibitory regulation of local circuitry normally differs across cortical regions of the visuospatial WM network and that in schizophrenia alterations of PV and SST neurons are a shared feature across these regions, whereas VIP neurons are affected only in V1.

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Khatri, Vivek, Randy M. Bruno et Daniel J. Simons. « Stimulus-Specific and Stimulus-Nonspecific Firing Synchrony and Its Modulation by Sensory Adaptation in the Whisker-to-Barrel Pathway ». Journal of Neurophysiology 101, n^o 5 (mai 2009) : 2328–38. http://dx.doi.org/10.1152/jn.91151.2008.

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The stimulus-evoked response of a cortical neuron depends on both details of the afferent signal and the momentary state of the larger network in which it is embedded. Consequently, identical sensory stimuli evoke highly variable responses. Using simultaneous recordings of thalamic barreloid and/or cortical barrel neurons in the rat whisker-to-barrel pathway, we determined the extent to which the responses of pairs of cells covary on a trial-by-trial basis. In the thalamus and cortical layer IV, a substantial component of trial-to-trial variability is independent of the specific parameters of the stimulus, probed here using deflection angle. These stimulus-nonspecific effects resulted in greater-than-chance similarities in trial-averaged angular tuning among simultaneously recorded pairs of barrel neurons. Such effects were not observed among simultaneously recorded thalamic and cortical barrel neurons, suggesting strong intracortical mechanisms of synchronization. Sensory adaptation produced by prior whisker deflections reduced response magnitudes and enhanced the joint angular tuning of simultaneously recorded neurons. Adaptation also decorrelated stimulus-evoked responses, rendering trial-by-trial responses of neuron pairs less similar to each other. Adaptation-induced decorrelation coupled with sharpened joint tuning could enhance the saliency of cells within thalamus or cortex that continue to fire synchronously during ongoing tactile stimulation associated with active touch.

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Nick, Christoph, Sandeep Yadav, Ravi Joshi, Christiane Thielemann et Jörg J. Schneider. « Growth and structural discrimination of cortical neurons on randomly oriented and vertically aligned dense carbon nanotube networks ». Beilstein Journal of Nanotechnology 5 (17 septembre 2014) : 1575–79. http://dx.doi.org/10.3762/bjnano.5.169.

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The growth of cortical neurons on three dimensional structures of spatially defined (structured) randomly oriented, as well as on vertically aligned, carbon nanotubes (CNT) is studied. Cortical neurons are attracted towards both types of CNT nano-architectures. For both, neurons form clusters in close vicinity to the CNT structures whereupon the randomly oriented CNTs are more closely colonised than the CNT pillars. Neurons develop communication paths via neurites on both nanoarchitectures. These neuron cells attach preferentially on the CNT sidewalls of the vertically aligned CNT architecture instead than onto the tips of the individual CNT pillars.

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Sadeh, Sadra, et Claudia Clopath. « Theory of neuronal perturbome in cortical networks ». Proceedings of the National Academy of Sciences 117, n^o 43 (14 octobre 2020) : 26966–76. http://dx.doi.org/10.1073/pnas.2004568117.

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To unravel the functional properties of the brain, we need to untangle how neurons interact with each other and coordinate in large-scale recurrent networks. One way to address this question is to measure the functional influence of individual neurons on each other by perturbing them in vivo. Application of such single-neuron perturbations in mouse visual cortex has recently revealed feature-specific suppression between excitatory neurons, despite the presence of highly specific excitatory connectivity, which was deemed to underlie feature-specific amplification. Here, we studied which connectivity profiles are consistent with these seemingly contradictory observations, by modeling the effect of single-neuron perturbations in large-scale neuronal networks. Our numerical simulations and mathematical analysis revealed that, contrary to the prima facie assumption, neither inhibition dominance nor broad inhibition alone were sufficient to explain the experimental findings; instead, strong and functionally specific excitatory–inhibitory connectivity was necessary, consistent with recent findings in the primary visual cortex of rodents. Such networks had a higher capacity to encode and decode natural images, and this was accompanied by the emergence of response gain nonlinearities at the population level. Our study provides a general computational framework to investigate how single-neuron perturbations are linked to cortical connectivity and sensory coding and paves the road to map the perturbome of neuronal networks in future studies.

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HAYOT, FERNAND, et DANIEL TRANCHINA. « Modeling corticofugal feedback and the sensitivity of lateral geniculate neurons to orientation discontinuity ». Visual Neuroscience 18, n^o 6 (novembre 2001) : 865–77. http://dx.doi.org/10.1017/s0952523801186037.

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We model feedback from primary visual cortex to the dorsal lateral geniculate nucleus (dLGN). This feedback makes dLGN neurons sensitive to orientation discontinuity (Sillito et al., 1993; Cudeiro & Sillito, 1996). In the model, each dLGN neuron receives retinotopic input driven by layer 6 cortical neurons in a full set of orientation columns. Excitation is monosynaptic, while inhibition is through perigeniculate neurons and dLGN interneurons. The stimulus consists of drifting gratings, one within and the other outside a circular region centered over the receptive field of the model dLGN relay neuron we study. They appear as a single grating when they are aligned with equal contrast. The model reproduces experimental results showing an increasing inhibitory effect of feedback on the firing rate of dLGN neurons as the two gratings move towards the aligned position. Moreover, enhancement of dLGN cell center-surround antagonism by feedback is revealed by measuring the responses to drifting gratings inside a circular window, as a function of window radius. This effect is related to the observed length tuning of dLGN cells. Sensitivity to orientation discontinuity could be mediated in the model by feedback from either simple or complex cells. The model puts constraints on the feedback synaptic footprint and shows that its elongated shape does not play a crucial role in sensitivity to orientation discontinuity. The inhibitory component of feedback must predominate overall, but the feedback signal from a cortical neuron to a dLGN neuron with the same or nearby receptive-field center can be dominated by excitation. Predictions of the model include (1) robust stimuli for layer 6 cortical neurons give pronounced nonlinearities in the responses of dLGN neurons; (2) the sensitivity to orientation discontinuity at low contrast is twice that at high contrast.

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Jia, Xiaoxuan, Joshua H. Siegle, Corbett Bennett, Samuel D. Gale, Daniel J. Denman, Christof Koch et Shawn R. Olsen. « High-density extracellular probes reveal dendritic backpropagation and facilitate neuron classification ». Journal of Neurophysiology 121, n^o 5 (1 mai 2019) : 1831–47. http://dx.doi.org/10.1152/jn.00680.2018.

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Different neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morphoelectrical properties of neurons measured on spatially dense electrode arrays have the potential to distinguish neuron types. We used high-density silicon probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multichannel compared with single-channel waveforms. In visual cortex, unsupervised clustering identified the canonical regular-spiking (RS) and fast-spiking (FS) classes but also indicated a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spikes from high-density probes aids neuron identification and can reveal dendritic backpropagation. NEW & NOTEWORTHY It is challenging to identify neuron types with extracellular electrophysiology in vivo. We show that spatiotemporal action potentials measured on high-density electrode arrays can capture cell type-specific morphoelectrical properties, allowing classification of neurons across brain structures and within the cortex. Moreover, backpropagating action potentials are reliably detected in vivo from subpopulations of cortical and hippocampal neurons. Together, these results enhance the utility of dense extracellular electrophysiology for cell-type interrogation of brain network function.

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Ratié, Leslie, Elodie Desmaris, Fernando García-Moreno, Anna Hoerder-Suabedissen, Alexandra Kelman, Thomas Theil, Eric J. Bellefroid et Zoltán Molnár. « Loss of Dmrt5 Affects the Formation of the Subplate and Early Corticogenesis ». Cerebral Cortex 30, n^o 5 (16 décembre 2019) : 3296–312. http://dx.doi.org/10.1093/cercor/bhz310.

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Abstract Dmrt5 (Dmrta2) and Dmrt3 are key regulators of cortical patterning and progenitor proliferation and differentiation. In this study, we show an altered apical to intermediate progenitor transition, with a delay in SP neurogenesis and premature birth of Ctip2+ cortical neurons in Dmrt5−/− mice. In addition to the cortical progenitors, DMRT5 protein appears present in postmitotic subplate (SP) and marginal zone neurons together with some migrating cortical neurons. We observed the altered split of preplate and the reduced SP and disturbed radial migration of cortical neurons into cortical plate in Dmrt5−/− brains and demonstrated an increase in the proportion of multipolar cells in primary neuronal cultures from Dmrt5−/− embryonic brains. Dmrt5 affects cortical development with specific time sensitivity that we described in two conditional mice with slightly different deletion time. We only observed a transient SP phenotype at E15.5, but not by E18.5 after early (Dmrt5lox/lox;Emx1Cre), but not late (Dmrt5lox/lox;NestinCre) deletion of Dmrt5. SP was less disturbed in Dmrt5lox/lox;Emx1Cre and Dmrt3−/− brains than in Dmrt5−/− and affects dorsomedial cortex more than lateral and caudal cortex. Our study demonstrates a novel function of Dmrt5 in the regulation of early SP formation and radial cortical neuron migration. Summary Statement Our study demonstrates a novel function of Dmrt5 in regulating marginal zone and subplate formation and migration of cortical neurons to cortical plate.

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Mikhailova, Alexandra, Naveena Sunkara et Patrick S. McQuillen. « Unbiased Quantification of Subplate Neuron Loss following Neonatal Hypoxia-Ischemia in a Rat Model ». Developmental Neuroscience 39, n^o 1-4 (2017) : 171–81. http://dx.doi.org/10.1159/000460815.

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Background: Cellular targets of neonatal hypoxia-ischemia (HI) include both oligodendrocyte and neuronal lineages with differences in the patterns of vulnerable cells depending upon the developmental stage at which the injury occurs. Injury to the developing white matter is a characteristic feature of human preterm brain injury. Data are accumulating, however, for neuronal injury in the developing cerebral cortex. In the most widely used rodent model of preterm HI brain injury, conflicting data have been reported regarding the sensitivity of subplate neurons to early neonatal HI, with some reports of selective vulnerability and others that find no increased loss of subplate neurons in comparison with other cortical layers. Methods used to identify subplate neurons and quantify their numbers vary across studies. Objective: To use recently developed cortical layer-specific markers quantified with definitive stereologic methods to determine the magnitude and specificity of subplate neuron cell loss following neonatal HI in a rodent model. Methods: Postnatal day 2 (P2) rats underwent right common carotid artery coagulation followed by 2-3 h of hypoxia (5.6% oxygen). Categorically moderately injured brains were stained with subplate and cortical layer III-V markers (Complexin3 and Foxp1, respectively) at P8 and P21 (Foxp1 only). An Optical Fractionator was used to quantify subplate and middle/lower cortical neuronal numbers and these were compared across groups (naive control, hypoxia hemisphere, and HI hemisphere). Results: Following HI at P2 in rats, the total Complexin3-expressing subplate neuron number decreases significantly in the HI hemisphere compared with naive controls or hypoxia alone (HI vs. control 26,747 ± 7,952 vs. 35,468 ± 8,029, p = 0.04; HI vs. hypoxia, 26,747 ± 7,952 vs. 40,439 ± 7,363, p = 0.003). In contrast, the total Foxp1-expressing layer III-V cell number did not differ across the 3 conditions at P8 (HI vs. control 1,195,085 ± 436,609 vs. 1,234,640 ± 178,540, p = 0.19; HI vs. hypoxia, 1,195,085 ± 436,609 vs. 1,289,195 ± 468,941, p = 0.35) and at P21 (HI vs. control 1,265,190 ± 48,089 vs. 1,195,632 ± 26,912, p = 0.19; HI vs. hypoxia, 1,265,190 ± 48,089 vs. 1,309,563 ± 41,669, p = 0.49). Conclusions: There is significant biological variability inherent in both the subplate neuron cell number and the pattern and severity of cortical injury following HI at P2 in rats. Despite this variability, the subplate neuron cell number is lower following P2 HI in animals with mild or moderate cortical injury, whereas the middle-to-lower-layer cortical neuronal number is unchanged. In more severe cases, neurons are lost from the lower cortical layers, suggesting a relative vulnerability of subplate neurons.

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Liu, X.-S., X.-L. Bai, Z.-X. Wang, S.-Y. Xu, Y. Ma et Z.-N. Wang. « Nrf2 mediates the neuroprotective effect of isoflurane preconditioning in cortical neuron injury induced by oxygen-glucose deprivation ». Human & ; Experimental Toxicology 40, n^o 7 (29 janvier 2021) : 1163–72. http://dx.doi.org/10.1177/0960327121989416.

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Objective: To investigate how nuclear factor-E2-related factor 2 (Nrf2) involved in the protective effect of isoflurane (Iso) preconditioning in oxygen glucose deprivation (OGD)-induced cortical neuron injury. Methods: Primary mouse cortical neurons were divided into Control, ML385 (an Nrf2 inhibitor), Iso, Iso + ML385, OGD, ML385 + OGD, Iso + OGD, and Iso + ML385 + OGD groups. Lactate dehydrogenase activity (LDH) release and oxidative stress indexes were quantified. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability, Annexin V-FITC/propidium iodide (PI) staining to measure cell apoptosis, dichloro-dihydro-fluorescein diacetate (DCFH-DA) method to test reactive oxygen species (ROS), and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting to evaluate genes and protein expression. Results: Iso preconditioning reduced LDH release and inhibited cell cytotoxicity in OGD-induced cortical neurons, which was abolished by ML385. Iso preconditioning increased the Nrf2 nuclear translocation in cortical neurons. Meanwhile, Iso decreased the OGD-induced apoptosis with the down-regulations of Bax and Caspase-3 and the up-regulation of Bcl-2, which was reversed by ML385. OGD enhanced the level of ROS and malondialdehyde (MDA) in cortical neurons, but reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which were aggravated in ML385 + OGD group and mitigated in Iso + OGD group. No observable difference was found between OGD group and Iso + ML385 + OGD group regarding apoptosis-related proteins and oxidative stress-related indexes. Conclusion: Iso preconditioning up-regulated Nrf2 level to play its protective role in OGD-induced mouse cortical neuron injury.

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Reid, C. B., S. F. Tavazoie et C. A. Walsh. « Clonal dispersion and evidence for asymmetric cell division in ferret cortex ». Development 124, n^o 12 (15 juin 1997) : 2441–50. http://dx.doi.org/10.1242/dev.124.12.2441.

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Cell lineage analysis with retroviral libraries suggests that clonal progeny disperse widely in rodent cortex. To determine whether widespread dispersion is a general mammalian plan and to investigate phylogenetic differences in cortical development, we analyzed cell lineage in the ferret, a carnivore and near relative of the cat. The ferret possesses a highly developed, folded cerebral cortex, characteristic of higher mammalian species. Progenitor cells of the ferret cerebral cortex were tagged with an amphotropic retroviral library encoding alkaline phosphatase, and sibling relationships were determined using the polymerase chain reaction. Neuronal clones were single neurons (52%) or large clones (48%; average, 7 neurons) containing neurons and glia in widespread cortical locations. Neuronal clones in the ferret labeled at middle to late neurogenesis (embryonic day 33–35) contained large numbers of neurons and showed little tendency to cluster. The large proportion of single neuron clones, contrasted with the large size of multicell clones, suggests that some progenitors divide asymmetrically, producing a postmitotic neuron and regenerating a multipotential cell.

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Duque, A., B. Balatoni, L. Detari et L. Zaborszky. « EEG Correlation of the Discharge Properties of Identified Neurons in the Basal Forebrain ». Journal of Neurophysiology 84, n^o 3 (1 septembre 2000) : 1627–35. http://dx.doi.org/10.1152/jn.2000.84.3.1627.

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The basal forebrain (BF) is a heterogeneous structure located in the ventral aspect of the cerebral hemispheres. It contains cholinergic as well as different types of noncholinergic corticopetal neurons and interneurons, including GABAergic and peptidergic cells. The BF constitutes an extrathalamic route to the cortex, and its activity is associated with an increase in cortical release of the neurotransmitter acetylcholine, concomitant with electroencephalographic (EEG) low-voltage fast activity (LVFA). However, the specific role of the different BF cell types has largely remained unknown due to the lack of chemical identification of the recorded neurons. Here we show that the firing rate of immunocytochemically identified cholinergic and parvalbumin-containing neurons increase during cortical LVFA. In contrast, increased neuropeptide Y neuron firing is accompanied by cortical slow waves. Our results, furthermore, indicate that BF neurons posses a distinct temporal relationship to different EEG patterns and suggest a more dynamic interplay within BF as well as between BF and cortical circuitries than previously proposed.

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Wertz, Adrian, Stuart Trenholm, Keisuke Yonehara, Daniel Hillier, Zoltan Raics, Marcus Leinweber, Gergely Szalay et al. « Single-cell–initiated monosynaptic tracing reveals layer-specific cortical network modules ». Science 349, n^o 6243 (2 juillet 2015) : 70–74. http://dx.doi.org/10.1126/science.aab1687.

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Individual cortical neurons can selectively respond to specific environmental features, such as visual motion or faces. How this relates to the selectivity of the presynaptic network across cortical layers remains unclear. We used single-cell–initiated, monosynaptically restricted retrograde transsynaptic tracing with rabies viruses expressing GCaMP6s to image, in vivo, the visual motion–evoked activity of individual layer 2/3 pyramidal neurons and their presynaptic networks across layers in mouse primary visual cortex. Neurons within each layer exhibited similar motion direction preferences, forming layer-specific functional modules. In one-third of the networks, the layer modules were locked to the direction preference of the postsynaptic neuron, whereas for other networks the direction preference varied by layer. Thus, there exist feature-locked and feature-variant cortical networks.

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Contreras, Diego, Niklaus Dürmüller et Mircea Steriade. « Absence of a Prevalent Laminar Distribution of IPSPs in Association Cortical Neurons of Cat ». Journal of Neurophysiology 78, n^o 5 (1 novembre 1997) : 2742–53. http://dx.doi.org/10.1152/jn.1997.78.5.2742.

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Contreras, Diego, Niklaus Dürmüller, and Mircea Steriade. Absence of a prevalent laminar distribution of IPSPs in association cortical neurons of cat. J. Neurophysiol. 78: 2742–2753, 1997. The depth distribution of inhibitory postsynaptic potentials (IPSPs) was studied in cat suprasylvian (association) cortex in vivo. Single and dual simultaneous intracellular recordings from cortical neurons were performed in the anterior part of suprasylvian gyrus (area 5). Synaptic responses were obtained by stimulating the suprasylvian cortex, 2–3 mm anterior to the recording site, as well as the thalamic lateral posterior (LP) nucleus. Neurons were recorded from layers 2 to 6 and were classified as regular spiking (RS, n = 132), intrinsically bursting (IB, n = 24), and fast spiking (FS, n = 4). Most IB cells were located in deep layers (below 0.7 mm, n = 19), but we also found some IB cells more superficially (between 0.2 and 0.5 mm, n = 5). Deeply lying corticothalamic neurons were identified by their antidromic invasion on thalamic stimulation. Neurons responded with a combination of excitatory postsynaptic potentials (EPSPs) and IPSPs to both cortical and thalamic stimulation. No consistent relation was found between cell type or cell depth and the amplitude or duration of the IPSPs. In response to thalamic stimulation, RS cells had IPSPs of 7.9 ± 0.9 (SE) mV amplitude and 88.9 ± 6.4 ms duration. In IB cells, IPSPs elicited by thalamic stimulation had 7.4 ± 1.3 mV amplitude and 84.7 ± 14.3 ms duration. The differences between the two (RS and IB) groups were not statistically significant. Compared with thalamically elicited inhibitory responses, cortical stimulation evoked IPSPs with higher amplitude (12.3 ± 1.7 mV) and longer duration (117 ± 17.3 ms) at all depths. Both cortically and thalamically evoked IPSPs were predominantly monophasic. Injections of Cl− fully reversed thalamically as well as cortically evoked IPSPs and revealed additional late synaptic components in response to cortical stimulation. These data show that the amount of feed forward and feedback inhibition to cat's cortical association cells is not orderly distributed to distinct layers. Thus local cortical microcircuitry goes beyond the simplified structure determined by cortical layers.

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Hahn, Maria A., Seung-Gi Jin, Arthur X. Li, Jiancheng Liu, Zhijun Huang, Xiwei Wu, Byung-Wook Kim et al. « Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical neuron differentiation ». Science Advances 5, n^o 10 (octobre 2019) : eaax0080. http://dx.doi.org/10.1126/sciadv.aax0080.

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The characteristics of DNA methylation changes that occur during neurogenesis in vivo remain unknown. We used whole-genome bisulfite sequencing to quantitate DNA cytosine modifications in differentiating neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. Localized DNA hypomethylation was much more common than hypermethylation and often occurred at putative enhancers within genes that were upregulated in neurons and encoded proteins crucial for neuronal differentiation. The hypomethylated regions strongly overlapped with mapped binding sites of the key neuronal transcription factor NEUROD2. The 5-methylcytosine oxidase ten-eleven translocation 2 (TET2) interacted with NEUROD2, and its reaction product 5-hydroxymethylcytosine accumulated at the demethylated regions. NEUROD2-targeted differentially methylated regions retained higher methylation levels in Neurod2 knockout mice, and inducible expression of NEUROD2 caused TET2-associated demethylation at its in vivo binding sites. The data suggest that the reorganization of DNA methylation in developing neurons involves NEUROD2 and TET2-mediated DNA demethylation.

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Raffi, Milena, Alessandro Piras, Roberta Calzavara et Salvatore Squatrito. « Area PEc Neurons Use a Multiphasic Pattern of Activity to Signal the Spatial Properties of Optic Flow ». BioMed Research International 2017 (2017) : 1–9. http://dx.doi.org/10.1155/2017/6495872.

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The cortical representation of visual perception requires the integration of several-signal processing distributed across many cortical areas, but the neural substrates of such perception are largely unknown. The type of firing pattern exhibited by single neurons is an important indicator of dynamic circuitry within or across cortical areas. Neurons in area PEc are involved in the spatial mapping of the visual field; thus, we sought to analyze the firing pattern of activity of PEc optic flow neurons to shed some light on the cortical processing of visual signals. We quantified the firing activity of 152 optic flow neurons using a spline interpolation function, which allowed determining onset, end, and latency of each neuronal response. We found that many PEc neurons showed multiphasic activity, which is strictly related to the position of the eye and to the position of the focus of expansion (FOE) of the flow field. PEc neurons showed a multiphasic activity comprised of excitatory phases interspersed with inhibitory pauses. This phasic pattern seems to be a very efficient way to signal the spatial location of visual stimuli, given that the same neuron sends different firing patterns according to a specific combination of FOE/eye position.

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Llamosas, Nerea, Sheldon D. Michaelson, Thomas Vaissiere, Camilo Rojas, Courtney A. Miller et Gavin Rumbaugh. « Syngap1 regulates experience-dependent cortical ensemble plasticity by promoting in vivo excitatory synapse strengthening ». Proceedings of the National Academy of Sciences 118, n^o 34 (17 août 2021) : e2100579118. http://dx.doi.org/10.1073/pnas.2100579118.

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A significant proportion of autism risk genes regulate synapse function, including plasticity, which is believed to contribute to behavioral abnormalities. However, it remains unclear how impaired synapse plasticity contributes to network-level processes linked to adaptive behaviors, such as experience-dependent ensemble plasticity. We found that Syngap1, a major autism risk gene, promoted measures of experience-dependent excitatory synapse strengthening in the mouse cortex, including spike-timing–dependent glutamatergic synaptic potentiation and presynaptic bouton formation. Synaptic depression and bouton elimination were normal in Syngap1 mice. Within cortical networks, Syngap1 promoted experience-dependent increases in somatic neural activity in weakly active neurons. In contrast, plastic changes to highly active neurons from the same ensemble that paradoxically weaken with experience were unaffected. Thus, experience-dependent excitatory synapse strengthening mediated by Syngap1 shapes neuron-specific plasticity within cortical ensembles. We propose that other genes regulate neuron-specific weakening within ensembles, and together, these processes function to redistribute activity within cortical networks during experience.

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Clark, Courtney M., Rosemary M. Clark, Joshua A. Hoyle, Jyoti A. Chuckowree, Catriona A. McLean et Tracey C. Dickson. « Differential NPY-Y1 Receptor Density in the Motor Cortex of ALS Patients and Familial Model of ALS ». Brain Sciences 11, n^o 8 (23 juillet 2021) : 969. http://dx.doi.org/10.3390/brainsci11080969.

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Destabilization of faciliatory and inhibitory circuits is an important feature of corticomotor pathology in amyotrophic lateral sclerosis (ALS). While GABAergic inputs to upper motor neurons are reduced in models of the disease, less understood is the involvement of peptidergic inputs to upper motor neurons in ALS. The neuropeptide Y (NPY) system has been shown to confer neuroprotection against numerous pathogenic mechanisms implicated in ALS. However, little is known about how the NPY system functions in the motor system. Herein, we investigate post-synaptic NPY signaling on upper motor neurons in the rodent and human motor cortex, and on cortical neuron populations in vitro. Using immunohistochemistry, we show the increased density of NPY-Y1 receptors on the soma of SMI32-positive upper motor neurons in post-mortem ALS cases and SOD1G93A excitatory cortical neurons in vitro. Analysis of receptor density on Thy1-YFP-H-positive upper motor neurons in wild-type and SOD1G93A mouse tissue revealed that the distribution of NPY-Y1 receptors was changed on the apical processes at early-symptomatic and late-symptomatic disease stages. Together, our data demonstrate the differential density of NPY-Y1 receptors on upper motor neurons in a familial model of ALS and in ALS cases, indicating a novel pathway that may be targeted to modulate upper motor neuron activity.

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McKenna, William L., Christian F. Ortiz-Londono, Thomas K. Mathew, Kendy Hoang, Sol Katzman et Bin Chen. « Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex ». Proceedings of the National Academy of Sciences 112, n^o 37 (31 août 2015) : 11702–7. http://dx.doi.org/10.1073/pnas.1504144112.

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Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequence-binding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.

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Buren, Caodu, Gaqi Tu, Matthew P. Parsons, Marja D. Sepers et Lynn A. Raymond. « Influence of cortical synaptic input on striatal neuronal dendritic arborization and sensitivity to excitotoxicity in corticostriatal coculture ». Journal of Neurophysiology 116, n^o 2 (1 août 2016) : 380–90. http://dx.doi.org/10.1152/jn.00933.2015.

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Corticostriatal cocultures are utilized to recapitulate the cortex-striatum connection in vitro as a convenient model to investigate the development, function, and regulation of synapses formed between cortical and striatal neurons. However, optimization of this dissociated neuronal system to more closely reproduce in vivo circuits has not yet been explored. We studied the effect of varying the plating ratio of cortical to striatal neurons on striatal spiny projection neuron (SPN) characteristics in primary neuronal cocultures. Despite the large difference in cortical-striatal neuron ratio (1:1 vs. 1:3) at day of plating, by 18 days in vitro the difference became modest (∼25% lower cortical-striatal neuron ratio in 1:3 cocultures) and the neuronal density was lower in the 1:3 cocultures, indicating enhanced loss of striatal SPNs. Comparing SPNs in cocultures plated at a 1:1 vs. 1:3 ratio, we found that resting membrane potential, input resistance, current injection-induced action potential firing rates, and input-output curves were similar in the two conditions. However, SPNs in the cocultures plated at the lower cortical ratio exhibited reduced membrane capacitance along with significantly shorter total dendritic length, decreased dendritic complexity, and fewer excitatory synapses, consistent with their trend toward reduced miniature excitatory postsynaptic current frequency. Strikingly, the proportion of NMDA receptors found extrasynaptically in recordings from SPNs was significantly higher in the less cortical coculture. Consistently, SPNs in cocultures with reduced cortical input showed decreased basal pro-survival signaling through cAMP response element binding protein and enhanced sensitivity to NMDA-induced apoptosis. Altogether, our study indicates that abundance of cortical input regulates SPN dendritic arborization and survival/death signaling.

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Cissé, Youssouf, François Grenier, Igor Timofeev et Mircea Steriade. « Electrophysiological Properties and Input-Output Organization of Callosal Neurons in Cat Association Cortex ». Journal of Neurophysiology 89, n^o 3 (1 mars 2003) : 1402–13. http://dx.doi.org/10.1152/jn.0871.2002.

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Intracellular recordings from association cortical areas 5 and 7 were performed in cats under barbiturate or ketamine-xylazine anesthesia to investigate the activities of different classes of neurons involved in callosal pathways, which were electrophysiologically characterized by depolarizing current steps. Excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), and/or antidromic responses were elicited by stimulating homotopic sites in the contralateral cortical areas. Differential features of EPSPs related to latencies, amplitudes, and slopes were detected in closely located (50 μm or less) neurons recorded in succession along the same electrode track. In contrast to synchronous thalamocortical volleys that excited most neurons within a cortical column, stimuli applied to homotopic sites in the contralateral cortex activated neurons at restricted cortical depths. Median latencies of callosally evoked EPSPs were 1.5 to 4 ms in various cortical cell-classes. Fast-rhythmic-bursting neurons displayed EPSPs whose amplitudes were threefold larger, and latencies two- or threefold shorter, than those found in the three other cellular classes. Converging callosal and thalamic inputs were recorded in the same cortical neuron. EPSPs or IPSPs were elicited by stimulating foci spaced by <1 mm in the contralateral cortex. In the overwhelming majority of neurons, latencies of antidromic responses were between 1.2 and 3.1 ms; however, some callosal neurons had much longer latencies, ≤18.5 ms. Some neurons were excited monosynaptically through the callosal pathway and identified antidromically from appropriate thalamic nuclei, thus revealing a callosal-corticothalamic pathway. Data are discussed in relation to the commissural spread of fast and slow normal oscillations as well as paroxysmal activities.

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Yuan, Wen, Sai Ma, Juliana R. Brown, Kwanho Kim, Vanessa Murek, Lucia Trastulla, Alexander Meissner et al. « Temporally divergent regulatory mechanisms govern neuronal diversification and maturation in the mouse and marmoset neocortex ». Nature Neuroscience 25, n^o 8 (août 2022) : 1049–58. http://dx.doi.org/10.1038/s41593-022-01123-4.

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AbstractMammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. Cortical neurons are born during embryonic development, and their maturation extends into postnatal life. The regulatory strategies underlying progressive neuronal development and maturation remain unclear. Here we present an integrated single-cell epigenomic and transcriptional analysis of individual mouse and marmoset cortical neuron classes, spanning both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We found that, in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use more widely shared and evolutionarily conserved molecular regulatory programs. In contrast, programs active during later neuronal maturation are more brain- and neuron-specific and more evolutionarily divergent. Our work uncovers a temporal shift in regulatory choices during neuronal diversification and maturation in both mice and marmosets, which likely reflects unique evolutionary constraints on distinct events of neuronal development in the neocortex.

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Zhang, Mengliang, et Kevin D. Alloway. « Stimulus-Induced Intercolumnar Synchronization of Neuronal Activity in Rat Barrel Cortex : A Laminar Analysis ». Journal of Neurophysiology 92, n^o 3 (septembre 2004) : 1464–78. http://dx.doi.org/10.1152/jn.01272.2003.

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We used cross-correlation analysis to characterize the coordination of stimulus-induced neuronal activity in the primary somatosensory barrel cortex of isoflurane-anesthetized rats. On each trial, multiple whiskers were simultaneously deflected at frequencies that corresponded to 2, 5, 8, or 11 Hz. Among 476 neuron pairs that we examined, 342 (71.8%) displayed significant peaks of synchronized activity that exceeded the 99.9% confidence limits. The incidence and strength of these functional associations varied across different cortical layers. Only 52.9% of neuron pairs in layer IV displayed synchronized responses, whereas 84.1% of the infragranular neuron pairs were synchronized during whisker stimulation. Neuronal synchronization was strongest in the infragranular layers, weakest in layer IV, and varied according to the columnar configuration of the neuron pairs. Thus correlation coefficients were largest for neuron pairs in the same whisker barrel row but were smallest for neurons in different rows and arcs. Spontaneous activity in the infragranular layers was also synchronized to a greater degree than in the other layers. Although infragranular neuron pairs displayed similar amounts of synchronization in response to each stimulus frequency, granular and supragranular neurons were synchronized mainly during stimulation at 2 or 5 Hz. These results are consistent with previous studies indicating that infragranular neurons have intrinsic properties that facilitate synchronized activity, and they suggest that neuronal synchronization plays an important role in transmitting sensory information to other cortical or subcortical brain regions.

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Faber, Samantha P., Nicholas M. Timme, John M. Beggs et Ehren L. Newman. « Computation is concentrated in rich clubs of local cortical networks ». Network Neuroscience 3, n^o 2 (janvier 2019) : 384–404. http://dx.doi.org/10.1162/netn_a_00069.

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To understand how neural circuits process information, it is essential to identify the relationship between computation and circuit organization. Rich clubs, highly interconnected sets of neurons, are known to propagate a disproportionate amount of information within cortical circuits. Here, we test the hypothesis that rich clubs also perform a disproportionate amount of computation. To do so, we recorded the spiking activity of on average ∼300 well-isolated individual neurons from organotypic cortical cultures. We then constructed weighted, directed networks reflecting the effective connectivity between the neurons. For each neuron, we quantified the amount of computation it performed based on its inputs. We found that rich-club neurons compute ∼160% more information than neurons outside of the rich club. The amount of computation performed in the rich club was proportional to the amount of information propagation by the same neurons. This suggests that in these circuits, information propagation drives computation. In total, our findings indicate that rich-club organization in effective cortical circuits supports not only information propagation but also neural computation.

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Kalaska, John F. « Emerging ideas and tools to study the emergent properties of the cortical neural circuits for voluntary motor control in non-human primates ». F1000Research 8 (29 mai 2019) : 749. http://dx.doi.org/10.12688/f1000research.17161.1.

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For years, neurophysiological studies of the cerebral cortical mechanisms of voluntary motor control were limited to single-electrode recordings of the activity of one or a few neurons at a time. This approach was supported by the widely accepted belief that single neurons were the fundamental computational units of the brain (the “neuron doctrine”). Experiments were guided by motor-control models that proposed that the motor system attempted to plan and control specific parameters of a desired action, such as the direction, speed or causal forces of a reaching movement in specific coordinate frameworks, and that assumed that the controlled parameters would be expressed in the task-related activity of single neurons. The advent of chronically implanted multi-electrode arrays about 20 years ago permitted the simultaneous recording of the activity of many neurons. This greatly enhanced the ability to study neural control mechanisms at the population level. It has also shifted the focus of the analysis of neural activity from quantifying single-neuron correlates with different movement parameters to probing the structure of multi-neuron activity patterns to identify the emergent computational properties of cortical neural circuits. In particular, recent advances in “dimension reduction” algorithms have attempted to identify specific covariance patterns in multi-neuron activity which are presumed to reflect the underlying computational processes by which neural circuits convert the intention to perform a particular movement into the required causal descending motor commands. These analyses have led to many new perspectives and insights on how cortical motor circuits covertly plan and prepare to initiate a movement without causing muscle contractions, transition from preparation to overt execution of the desired movement, generate muscle-centered motor output commands, and learn new motor skills. Progress is also being made to import optical-imaging and optogenetic toolboxes from rodents to non-human primates to overcome some technical limitations of multi-electrode recording technology.

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Jones, Edward G. « Neurotransmitters in the cerebral cortex ». Journal of Neurosurgery 65, n^o 2 (août 1986) : 135–53. http://dx.doi.org/10.3171/jns.1986.65.2.0135.

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✓ This article surveys the conventional neurotransmitters and modulatory neuropeptides that are found in the cerebral cortex and attempts to place them into the perspective of both intracortical circuitry and cortical disease. The distribution of these substances is related, where possible, to particular types of cortical neuron or to afferent or efferent fibers. Their physiological actions, where known, on cortical neurons are surveyed, and their potential roles in disease states such as the dementias, epilepsy, and stroke are assessed. Conventional transmitters that occur in afferent fibers to the cortex from brain-stem and basal forebrain sites are: serotonin, noradrenaline, dopamine, and acetylcholine. All of these except dopamine are distributed to all cortical areas: dopamine is distributed to frontal and cingulate areas only. The transmitter in thalamic afferent systems is unknown. Gamma aminobutyric acid (GABA) is the transmitter used by the majority of cortical interneurons and has a profound effect upon the shaping of receptive field properties. The vast majority of the known cortical peptides are found in GABAergic neurons, and the possibility exists that they may act as trophic substances for other neurons. Levels of certain neuropeptides decline in cases of dementia of cortical origin. Acetylcholine is the only other known transmitter of cortical neurons. It, too, is contained in neurons that also contain a neuropeptide. The transmitter(s) used by excitatory cortical interneurons and by the efferent pyramidal cells is unknown, but it may be glutamate or aspartate. It is possible that excitotoxins released in anoxic disease of the cortex may produce damage by acting on receptors for these or related transmitter agents.

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Bracci, Enrico, Diego Centonze, Giorgio Bernardi et Paolo Calabresi. « Engagement of Rat Striatal Neurons by Cortical Epileptiform Activity Investigated With Paired Recordings ». Journal of Neurophysiology 92, n^o 5 (novembre 2004) : 2725–37. http://dx.doi.org/10.1152/jn.00585.2004.

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The striatum is thought to play an important role in the spreading of epilepsy from cortical areas to deeper brain structures, but this issue has not been addressed with intracellular techniques. Paired recordings were used to assess the impact of cortical epileptiform activity on striatal neurons in brain slices. Bath-application of 4-amynopyridine (100 μM) and bicuculline (20 μM) induced synchronized bursts in all pairs of cortical neurons (≤5 mm apart) in coronal, sagittal, and oblique slices (which preserve connections from the medial agranular cortex to the striatum). Under these conditions, striatal medium spiny neurons (MSs) displayed a strong increased spontaneous glutamatergic activity. This activity was not correlated to the cortical bursts and was asynchronous in pairs of MSs. Sporadic, large-amplitude synchronous depolarizations also occurred in MSs. These events were simultaneously detected in glial cells, suggesting that they were accompanied by considerable increases in extracellular potassium. In oblique slices, cortically driven bursts were also observed in MSs. These events were synchronized to cortical epileptiform bursts, depended on non– N-methyl-d-aspartate (NMDA) glutamate receptors, and persisted in the cortex, but not in the striatum, after disconnection of the two structures. During these bursts, MS membrane potential shifted to a depolarized value (59 ± 4 mV) on which an irregular waveform, occasionally eliciting spikes, was superimposed. Thus synchronous activation of a limited set of corticostriatal afferents can powerfully control MSs. Cholinergic interneurons located <120 μm from simultaneously recorded MSs, did not display cortically driven bursts, suggesting that these cells are much less easily engaged by cortical epileptiform activity.

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Kim, Tae, Stephen Thankachan, James T. McKenna, James M. McNally, Chun Yang, Jee Hyun Choi, Lichao Chen et al. « Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations ». Proceedings of the National Academy of Sciences 112, n^o 11 (2 mars 2015) : 3535–40. http://dx.doi.org/10.1073/pnas.1413625112.

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Cortical gamma band oscillations (GBO, 30–80 Hz, typically ∼40 Hz) are involved in higher cognitive functions such as feature binding, attention, and working memory. GBO abnormalities are a feature of several neuropsychiatric disorders associated with dysfunction of cortical fast-spiking interneurons containing the calcium-binding protein parvalbumin (PV). GBO vary according to the state of arousal, are modulated by attention, and are correlated with conscious awareness. However, the subcortical cell types underlying the state-dependent control of GBO are not well understood. Here we tested the role of one cell type in the wakefulness-promoting basal forebrain (BF) region, cortically projecting GABAergic neurons containing PV, whose virally transduced fibers we found apposed cortical PV interneurons involved in generating GBO. Optogenetic stimulation of BF PV neurons in mice preferentially increased cortical GBO power by entraining a cortical oscillator with a resonant frequency of ∼40 Hz, as revealed by analysis of both rhythmic and nonrhythmic BF PV stimulation. Selective saporin lesions of BF cholinergic neurons did not alter the enhancement of cortical GBO power induced by BF PV stimulation. Importantly, bilateral optogenetic inhibition of BF PV neurons decreased the power of the 40-Hz auditory steady-state response, a read-out of the ability of the cortex to generate GBO used in clinical studies. Our results are surprising and novel in indicating that this presumptively inhibitory BF PV input controls cortical GBO, likely by synchronizing the activity of cortical PV interneurons. BF PV neurons may represent a previously unidentified therapeutic target to treat disorders involving abnormal GBO, such as schizophrenia.

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Sakakibara, Yasufumi, Yu Hirota, Kyoko Ibaraki, Kimi Takei, Sachie Chikamatsu, Yoko Tsubokawa, Takashi Saito, Takaomi C. Saido, Michiko Sekiya et Koichi M. Iijima. « Widespread Reduced Density of Noradrenergic Locus Coeruleus Axons in the App Knock-In Mouse Model of Amyloid-β Amyloidosis ». Journal of Alzheimer's Disease 82, n^o 4 (17 août 2021) : 1513–30. http://dx.doi.org/10.3233/jad-210385.

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Background: The locus coeruleus (LC), a brainstem nucleus comprising noradrenergic neurons, is one of the earliest regions affected by Alzheimer’s disease (AD). Amyloid-β (Aβ) pathology in the cortex in AD is thought to exacerbate the age-related loss of LC neurons, which may lead to cortical tau pathology. However, mechanisms underlying LC neurodegeneration remain elusive. Objective: Here, we aimed to examine how noradrenergic neurons are affected by cortical Aβ pathology in AppNL-G-F/NL-G-F knock-in mice. Methods: The density of noradrenergic axons in LC-innervated regions and the LC neuron number were analyzed by an immunohistochemical method. To explore the potential mechanisms for LC degeneration, we also examined the occurrence of tau pathology in LC neurons, the association of reactive gliosis with LC neurons, and impaired trophic support in the brains of AppNL-G-F/NL-G-F mice. Results: We observed a significant reduction in the density of noradrenergic axons from the LC in aged AppNL-G-F/NL-G-F mice without neuron loss or tau pathology, which was not limited to areas near Aβ plaques. However, none of the factors known to be related to the maintenance of LC neurons (i.e., somatostatin/somatostatin receptor 2, brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) were significantly reduced in AppNL-G-F/NL-G-F mice. Conclusion: This study demonstrates that cortical Aβ pathology induces noradrenergic neurodegeneration, and further elucidation of the underlying mechanisms will reveal effective therapeutics to halt AD progression.

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Li, Xing-Tong, Wei Ma, Xian-Bin Wang, Zhang Liang, Jin-Wei Yang, Yuan He, Yun-Fei Dai et al. « Notoginsenoside R1 Promotes the Growth of Neonatal Rat Cortical Neurons via the Wnt/β-catenin Signaling Pathway ». CNS & ; Neurological Disorders - Drug Targets 17, n^o 7 (29 août 2018) : 547–56. http://dx.doi.org/10.2174/1871527317666180711093538.

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Background & Objective: Notoginsenoside R1 (NGR1) is one of the main effective components of Panax notoginseng. Method: Primary cortical neurons were harvested from neonatal rats and cultured to analyze the role of NGR1 in neuronal growth and the effects of NGR1 on the Wnt/β-catenin signaling pathway. Following treatment with NGR1, immunocytochemistry was used to detect expression of Tuj1 and MAP2, and RT-qPCR was used to measure mRNA levels of key factors in the Wnt signaling pathway. Results: Results showed that NGR1 promotes growth of cultured neurons and significantly upregulates mRNA levels of β-catenin, Dishevelled, and Frizzled. To further confirm whether NGR1 promoted cortical neuron growth via the Wnt/β-catenin signaling pathway, we knocked down β- catenin mRNA by siRNA interference; following NGR1 treatment of β-catenin-knockdown neurons, β-catenin mRNA levels increased significantly. Conclusion: In conclusion, these results demonstrate that NGR1 promotes growth of cultured cortical neurons from the neonatal rat, possibly via the Wnt/β-catenin signaling pathway.

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Wei, Gang, Dong-Feng Chen, Xiao-Ping Lai, Dong-Hui Liu, Ru-Dong Deng, Jian-Hong Zhou, Sai-Xia Zhang, Yi-Wei Li, Hui Li et Qiong-Dan Zhang. « Muscone Exerts Neuroprotection in an Experimental Model of Stroke via Inhibition of the Fas Pathway ». Natural Product Communications 7, n^o 8 (août 2012) : 1934578X1200700. http://dx.doi.org/10.1177/1934578x1200700826.

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Identifying small molecules that are neuroprotective against stroke injury will be highly beneficial for treatment therapies. A cell viability assay and gas chromatography-mass spectrometry were used to identify active small molecules in XingNaoJing, which is a well known Chinese Medicine prescribed for the effective treatment of stroke. Studies have found that muscone is the active compound that prevents PC12 cell and cortical neuron damage following various injuries. Analysis of apoptosis indicated that muscone inhibited glutamate-induced apoptotic cell death of PC12 cells and cortical neurons. Fas and caspase-8 expression were upregulated following glutamate treatment in cortical neurons, and was markedly attenuated in the presence of muscone. Furthermore, muscone significantly reduced cerebral infarct volume, neurological dysfunction and inhibited cortical neuron apoptosis in middle cerebral artery occluded (MCAO) rats in a dose-dependent manner. Moreover, a significant decrease in Fas and caspase-8 expression in the rat cortex was observed in MCAO rats treated with muscone. Our results demonstrate that muscone may be a small active molecule with neuroprotective properties, and that inhibition of apoptosis and Fas is an important mechanism of neuroprotection by muscone. These findings suggest a potential therapeutic role for muscone in the treatment of stroke.

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