Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and...Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.展开更多
Recent studies show that a reduced effect of inhibitory transmitter system in the visual cortex may underlie aged visual function degradation. Whether excitatory transmitter system changes with age and hence affects i...Recent studies show that a reduced effect of inhibitory transmitter system in the visual cortex may underlie aged visual function degradation. Whether excitatory transmitter system changes with age and hence affects intracortical excitation-inhibition balance is not clear. To explore this issue, we used Nissl staining and immunohistochemical methods as well as Image-Pro Express software to examine the density of Nissl-stained neurons, Glutamie acid-immunoreactive （Glu-IR） neurons and T-Aminobutyric acid-immunoreactive （GABA-IR） neurons in the primary visual cortex of young adult and aged cats. The results showed that there was no significant difference in the density of Nissl-stained neurons between young and old cats （2〉0.05）. However, the density of Glu-IR neurons and GABA-IR neurons in the primary visual cortex of aged cats was significantly lower than that of young ones （P〈0.01）. The ratio between Glu-IR neurons and GABA-IR neurons was significantly increased in old cats compared to that in young adult ones （P〈0.01）. These results indicated that the effect of excitatory transmitter system in the old visual cortex was increased relative to the inhibitory transmitter system, which might cause an imbalance between cortical excitation and inhibition and might be an important factor mediating the visual function decline during aging.展开更多
Diffusion-weighted magnetic resonance imaging（d MRI） is widely used to study white and gray matter（GM） micro-organization and structural connectivity in the brain. Super-resolution track-density imaging（TDI） is ...Diffusion-weighted magnetic resonance imaging（d MRI） is widely used to study white and gray matter（GM） micro-organization and structural connectivity in the brain. Super-resolution track-density imaging（TDI） is an image reconstruction method for d MRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI（st TDI）, a variation of TDI with enhanced contrast for GM structures, to reconstruct directionencoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging（DTI） method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with st TDI,but not with DTI reconstructions from the same d MRI data.The possible mechanisms underlying the enhanced GM contrast are discussed.展开更多
Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons.Difficulty in the attentional task adjusts how much concentration we maintain on what is curr...Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons.Difficulty in the attentional task adjusts how much concentration we maintain on what is currently important and what is filtered as irrelevant sensory information.However,how task difficulty mediates the interactions between neurons with separated receptive fields(RFs)that are attended to or attended away is still not clear.We examined spike count correlations between single-unit activities recorded simultaneously in the primary visual cortex(V1)while monkeys performed a spatial attention task with two levels of difficulty.Moreover,the RFs of the two neurons recorded were non-overlapping to allow us to study fluctuations in the correlated responses between competing visual inputs when the focus of attention was allocated to the RF of one neuron.While increasing difficulty in the spatial attention task,spike count correlations were either decreased to become negative between neuronal pairs,implying competition among them,with one neuron(or none)exhibiting attentional enhancement of firing rate,or increased to become positive,suggesting inter-neuronal cooperation,with one of the pair showing attentional suppression of spiking responses.Besides,the modulation of spike count correlations by task difficulty was independent of the attended locations.These findings provide evidence that task difficulty affects the functional interactions between different neuronal pools in V1 when selective attention resolves the spatial competition.展开更多
It is disputed whether those neurons in the primary motor cortex（M1） that encode hand orientation constitute an independent channel for orientation control in reach-to-grasp behaviors. Here, we trained two monkeys t...It is disputed whether those neurons in the primary motor cortex（M1） that encode hand orientation constitute an independent channel for orientation control in reach-to-grasp behaviors. Here, we trained two monkeys to reach forward and grasp objects positioned in the frontal plane at different orientation angles, and simultaneously recorded the activity of M1 neurons. Among the 2235 neurons recorded in M1, we found that 18.7% had a high correlation exclusively with hand orientation, 15.9% with movement direction, and 29.5% with both movement direction and hand orientation. The distributions of neurons encoding hand orientation and those encoding movement direction were not uniform but coexisted in the same region. The trajectory of hand rotation was reproduced by the firing patterns of the orientation-related neurons independent of the hand reaching direction. These resultssuggest that hand orientation is an independent component for the control of reaching and grasping activity.展开更多
AIM： To evaluate the differences in the functional connectivity（FC） of the primary visual cortex（V1） between the youth comitant exotropia（CE） patients and health subjects using resting functional magnetic reson...AIM： To evaluate the differences in the functional connectivity（FC） of the primary visual cortex（V1） between the youth comitant exotropia（CE） patients and health subjects using resting functional magnetic resonance imaging（f MRI） data.METHODS： Totally, 32 CEs（25 males and 7 females） and 32 healthy control subjects（HCs）（25 males and 7 females） were enrolled in the study and underwent the MRI scanning. Two-sample t-test was used to examine differences in FC maps between the CE patients and HCs. RESULTS： The CE patients showed significantly less FC between the left brodmann area（BA17） and left lingual gyrus/cerebellum posterior lobe, right middle occipital gyrus, left precentral gyrus/postcentral gyrus and right inferior parietal lobule/postcentral gyrus. Meanwhile, CE patients showed significantly less FC between right BA17 and right middle occipital gyrus（BA19, 37）.CONCLUSION： Our findings show that CE involves abnormal FC in primary visual cortex in many regions, which may underlie the pathologic mechanism of impaired fusion and stereoscopic vision in CEs.展开更多
Major depressive disorder(MDD),characterized by anhedonia,loss of motivation,behavioral despair,and cognitive abnormalities[1],stands as the second leading cause of disability worldwide[2]owing to its heightened preva...Major depressive disorder(MDD),characterized by anhedonia,loss of motivation,behavioral despair,and cognitive abnormalities[1],stands as the second leading cause of disability worldwide[2]owing to its heightened prevalence,suicide rates,and recurrence[3].Empirical evidence and clinical observations have substantiated the notion that patients with MDD often exhibit compromised auditory perception[4].展开更多
Several recent studies using either viral or transgenic mouse models have shown different results on whether the activation of parvalbumin-positive（PV~＋）neurons expressing channelrhodopsin-2（ChR2） in the primary ...Several recent studies using either viral or transgenic mouse models have shown different results on whether the activation of parvalbumin-positive（PV~＋）neurons expressing channelrhodopsin-2（ChR2） in the primary visual cortex（V1） improves the orientation-and direction-selectivity of V1 neurons. Although this discrepancy was thoroughly discussed in a follow-up communication, the issue of using different models to express ChR2 in V1 was not mentioned. We found that ChR2 was expressed in retinal ganglion cells（RGCs） and V1 neurons in ChR2fl/~＋; PV-Cre mice. Our results showed that the activation of PV~＋RGCs using white drifting gratings alone significantly decreased the firing rates of V1 neurons and improved their direction-and orientation-selectivity. Longduration activation of PV~＋interneurons in V1 further enhanced the feature-selectivity of V1 neurons in anesthetized mice, confirming the conclusions from previous findings. These results suggest that the activation of both PV~＋RGCs and V1 neurons improves feature-selectivity in mice.展开更多
Fear memory contextualization is critical for selecting adaptive behavior to survive.Contextual fear conditioning(CFC)is a classical model for elucidating related underlying neuronal circuits.The primary visual cortex...Fear memory contextualization is critical for selecting adaptive behavior to survive.Contextual fear conditioning(CFC)is a classical model for elucidating related underlying neuronal circuits.The primary visual cortex(V1)is the primary cortical region for contextual visual inputs,but its role in CFC is poorly understood.Here,our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval,and both CFC learning and extinction increased the turnover rate of axonal boutons in V1.The frequency of neuronal Ca^(2+)activity decreased after CFC learning,while CFC extinction reversed the decrease and raised it to the naïve level.Contrary to control mice,the frequency of neuronal Ca^(2+)activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction,indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca^(2+)activity.These findings reveal a critical role of microglia in neocortical information processing in V1,and suggest potential approaches for cellular-based manipulation of acquired fear memory.展开更多
Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the pr...Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.展开更多
Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only ＂see＂ pixelized...Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only ＂see＂ pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex（the implant area） is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine（LSVM） as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern.展开更多
A better understanding of the neural mechanisms of finger-force regulation can help to explain the relationship between the central nervous system and nerve-muscle force, as well as assist in motor functional rehabili...A better understanding of the neural mechanisms of finger-force regulation can help to explain the relationship between the central nervous system and nerve-muscle force, as well as assist in motor functional rehabilitation and the development robot hand designs. In the present study, 11 healthy volunteers performed a different target force-tracking task, which involved the index finger alone, index and middle finger together, and the combination of four fingers （i.e., index, middle, ring, and little）. The target force trace corresponded to 3 levels of 20% maximal voluntary changes （MVC）, 30% MVC, and 40% MVC in 20 seconds. In the test, an unexpected single 120% motor threshold transcranial magnetic stimulation was applied to the primary motor cortex （M1） during force tracking. Results revealed that peak force changes increased with increasing background force and the number of involved task fingers. These results demonstrate that M1 neural activities correlate with finger-force production, and M1 plays a role in finger-force control. Moreover, different neuronal networks were required for different finger patterns; a complicated task required multi-finger combinations and a complicated neuronal network comprised a large number of neurons.展开更多
In this study,we investigated orientation selectivity in cat primary visual cortex（V1） and its relationship with various parameters.We found a strong correlation between circular variance（CV） and orthogonal-topref...In this study,we investigated orientation selectivity in cat primary visual cortex（V1） and its relationship with various parameters.We found a strong correlation between circular variance（CV） and orthogonal-topreferred response ratio（O/P ratio）,and a moderate correlation between tuning width and O/P ratio.Moreover,the suppression far from the peak that accounted for the lower CV in cat V1 cells also contributed to the narrowing of the tuning width of cells.We also studied the dependence of orientation selectivity on the modulation ratio for each cell,which is consistent with robust entrainment of the neuronal response to the phase of the drifting grating stimulus.In conclusion,the CV（global measure） and tuning width（local measure） are significantly correlated with the modulation ratio.展开更多
Background:Information about the visual world is processed by an ensemble of cortical visual areas,which follow a hierarchical organization.The primary visual cortex(V1)first receives most of this information through ...Background:Information about the visual world is processed by an ensemble of cortical visual areas,which follow a hierarchical organization.The primary visual cortex(V1)first receives most of this information through the lateral geniculate nucleus(LGN),before being conveyed to higher-order cortical areas.Aside from this connectional route,there is also a complex network of bilateral connections between areas of the visual cortex and the pulvinar,considered as the largest extrageniculate visual thalamic nucleus.Despite an increasing number of studies on pulvinar,the exact function of this thalamic complex remains unknown.In this study,we investigated the functional impact of the lateral posterior(LP)nucleus,the homologue of the primate pulvinar,on the activity of neurons in the primary visual cortex in mice using optogenetic stimulation.Methods:A channel rhodopsin-2 gene-carrying viral vector(AAV5.CaMKII.hChR2-eYFP.WPRE)was injected into the LP of wild-type(C57BL/6)mice.Extracellular recordings of the activity of V1 neurons were carried out using 16-and 32-channel silicon probes.The stimulation of LP was achieved with light pulses(470 nm,20 pulse trains of 5 ms each at 10 Hz)delivered by a 4-channel optrode,which also recorded the thalamic activity.Visual stimuli consisted on drifting sinewave gratings of varying parameters(direction,contrast,spatial or temporal frequency and size).Results:Our preliminary data shows that LP stimulation performed in conjunction with the visual stimulation decreases the amplitude of neuronal responses up to 50%.To date,results indicate that this inhibitory effect is only observed in neurons in the infragranular layers.The response profiles of V1 neurons to size-increasing stimuli were also affected.Conclusions:These findings suggest that the pulvinar nucleus can exert layer-dependent contextual modulation on the activity of neurons in the mouse primary visual cortex.展开更多
Background:The primary visual cortex(V1)is a key component of the visual system that builds some of the first levels of coherent visual representations from sparse visual inputs.While the study of its dynamics has bee...Background:The primary visual cortex(V1)is a key component of the visual system that builds some of the first levels of coherent visual representations from sparse visual inputs.While the study of its dynamics has been the focus of many computational models for the past years,there is still relatively few research works that put an emphasis on both synaptic plasticity in V1 and biorealism in the context of learning visual inputs.Here,we present a recurrent spiking neural network that is capable of spike timing dependent plasticity(STDP)and we demonstrate its capacity to discriminate spatio-temporal orientation patterns in noisy natural images.Methods:A two stage model was developed.First,natural images flux(be it videos/gratings/camera)were converted into spikes,using a difference of gaussians(DOG)approach.This transformation approximates the retina-lateral geniculate nucleus(LGN)organization.Secondly,a spiking neural network was build using PyNN simulator,mimicking cortical neurons dynamics and plasticity,as well as V1 topology.This network was then fed with spikes generated by the first model and its ability to build visual representations was assessed using control gratings inputs.Results:The neural network exhibited several interesting properties.After a short period of learning,it was capable of learning multiples orientations and reducing noise in such learned feature,compared to the inputs.These learned features were stable even after increasing the noise in inputs and were found to not only encoding the spatial properties of the input,but also its temporal aspects(i.e.,the time of each grating presentation Conclusions:Our work shows that topological structuring of the cortical neural networks,combined with simple plasticity rules,are sufficient to drive strong learning dynamics of natural images properties.This computational model fits many properties found in the literature and provides some theoritical explanations for the shape of tuning curve of certain layers of V1.Further investigations are now conducted to validate its properties against the neuronal responses of rodents,using identical visual stimuli.展开更多
Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta o...Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking. In this study, we set up an implicit motor timing task and found a modulation pattern of beta oscillations with temporal perception during movement preparation. We trained two macaques in a repetitive visually-guided reach-to-grasp task with different holding intervals. Spikes and local field potentials were recorded from microelectrode arrays in the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. We analyzed the association between beta oscillations and temporal interval in fixedduration experiments(500 ms as the Short Group and1500 ms as the Long Group) and random-duration experiments(500 ms to 1500 ms). The results showed that the peak beta frequencies in both experiments ranged from15 Hz to 25 Hz. The beta power was higher during the hold period than the movement(reach and grasp) period.Further, in the fixed-duration experiments, the mean poweras well as the maximum rate of change of beta power in the first 300 ms were higher in the Short Group than in the Long Group when aligned with the Center Hit event. In contrast, in the random-duration experiments, the corresponding values showed no statistical differences among groups. The peak latency of beta power was shorter in the Short Group than in the Long Group in the fixed-duration experiments, while no consistent modulation pattern was found in the random-duration experiments. These results indicate that beta oscillations can modulate with temporal interval in their power mode. The synchronization period of beta power could reflect the cognitive set maintaining working memory of the temporal structure and attention.展开更多
Nogo-A and Nogo receptor （NgR） expression in the visual cortex following a critical developmental period （postnatal days 20-60） has been previously shown. However, little is known regarding Nogo-A and NgR expressi...Nogo-A and Nogo receptor （NgR） expression in the visual cortex following a critical developmental period （postnatal days 20-60） has been previously shown. However, little is known regarding Nogo-A and NgR expression between postnatal day 0 and initiation of the critical period. The present study analyzed Nogo-A and NgR expression at four different time points： postnatal day 0 （P0）, before critical period （P14）, during critical period （P28）, and after critical period （P60）. Results showed significantly increased Nogo-A mRNA and protein expression levels in the visual cortex following birth, and expression levels remained steady between P28 and P60. NgR mRNA or protein expression was dramatically upregulated with age and peaked at P14 or P28, respectively, and maintained high expression to P60. In addition, Nogo-A and NgR expression was analyzed in each visual cortex layer in normal developing rats and rats with monocular deprivation. Monocular deprivation decreased Nogo-A and NgR mRNA and protein expression in the rat visual cortex, in particular in layers Ⅱ-Ⅲ and Ⅳ in the visual cortex contralateral to the deprived eye. These findings suggested that Nogo-A and NgR regulated termination of the critical period in experience- dependent visual cortical plasticity.展开更多
Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθo...Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθoscillation recorded during periods when L-dopa is withdrawn(the off L-dopa state).To gain insight into processes underlying this activity,we explored the relationship between primary motor cortex(M1)oscillatory activity and BG output in LID.We recorded local field potentials in the substantia nigra pars reticulata(SNr)and M1 of awake,inattentive resting rats before and after L-dopa priming in Sham control,Parkinson disease model,and LID model groups.We found that chronic L-dopa increasedθsynchronization and information flow between the SNr and M1 in off L-dopa state LID rats,with a SNr-to-M1 flow directionality.Compared with the on state,θoscillational activity(θsynchronization and informationflow)during the off state were more closely associated with abnormal involuntary movements.Our findings indicate thatθoscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1θoscillation may participate in the induction of dyskinesia.展开更多
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Cu...Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.展开更多
基金supported by the National Natural Science Foundation of China,Nos.62027812(to HS),81771470(to HS),and 82101608(to YL)Tianjin Postgraduate Research and Innovation Project,No.2020YJSS122(to XD)。
文摘Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.
基金Natural Science Fund of Anhui Province (070413138)Key Laboratory Foundation of Anhui Province for Researches on the Conservation and Utilization of Important Biological ResourceKey Laboratory Foundation for Universities and Colleges in Anhui
文摘Recent studies show that a reduced effect of inhibitory transmitter system in the visual cortex may underlie aged visual function degradation. Whether excitatory transmitter system changes with age and hence affects intracortical excitation-inhibition balance is not clear. To explore this issue, we used Nissl staining and immunohistochemical methods as well as Image-Pro Express software to examine the density of Nissl-stained neurons, Glutamie acid-immunoreactive （Glu-IR） neurons and T-Aminobutyric acid-immunoreactive （GABA-IR） neurons in the primary visual cortex of young adult and aged cats. The results showed that there was no significant difference in the density of Nissl-stained neurons between young and old cats （2〉0.05）. However, the density of Glu-IR neurons and GABA-IR neurons in the primary visual cortex of aged cats was significantly lower than that of young ones （P〈0.01）. The ratio between Glu-IR neurons and GABA-IR neurons was significantly increased in old cats compared to that in young adult ones （P〈0.01）. These results indicated that the effect of excitatory transmitter system in the old visual cortex was increased relative to the inhibitory transmitter system, which might cause an imbalance between cortical excitation and inhibition and might be an important factor mediating the visual function decline during aging.
基金supported by grants from the National Basic Research Development Program of China (2011CB707800)the National Natural Science Foundation of China (21790390, 21790392, and 61371014)
文摘Diffusion-weighted magnetic resonance imaging（d MRI） is widely used to study white and gray matter（GM） micro-organization and structural connectivity in the brain. Super-resolution track-density imaging（TDI） is an image reconstruction method for d MRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI（st TDI）, a variation of TDI with enhanced contrast for GM structures, to reconstruct directionencoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging（DTI） method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with st TDI,but not with DTI reconstructions from the same d MRI data.The possible mechanisms underlying the enhanced GM contrast are discussed.
基金This work was supported by the National Natural Science Foundation of China(61773259,31471081,61773256,62073221,and 61971280).
文摘Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons.Difficulty in the attentional task adjusts how much concentration we maintain on what is currently important and what is filtered as irrelevant sensory information.However,how task difficulty mediates the interactions between neurons with separated receptive fields(RFs)that are attended to or attended away is still not clear.We examined spike count correlations between single-unit activities recorded simultaneously in the primary visual cortex(V1)while monkeys performed a spatial attention task with two levels of difficulty.Moreover,the RFs of the two neurons recorded were non-overlapping to allow us to study fluctuations in the correlated responses between competing visual inputs when the focus of attention was allocated to the RF of one neuron.While increasing difficulty in the spatial attention task,spike count correlations were either decreased to become negative between neuronal pairs,implying competition among them,with one neuron(or none)exhibiting attentional enhancement of firing rate,or increased to become positive,suggesting inter-neuronal cooperation,with one of the pair showing attentional suppression of spiking responses.Besides,the modulation of spike count correlations by task difficulty was independent of the attended locations.These findings provide evidence that task difficulty affects the functional interactions between different neuronal pools in V1 when selective attention resolves the spatial competition.
基金supported by the National Natural Science Foundation of China(61233015 and 31460263)the National Basic Research Development Program(973 Program)of China(2013CB329506)
文摘It is disputed whether those neurons in the primary motor cortex（M1） that encode hand orientation constitute an independent channel for orientation control in reach-to-grasp behaviors. Here, we trained two monkeys to reach forward and grasp objects positioned in the frontal plane at different orientation angles, and simultaneously recorded the activity of M1 neurons. Among the 2235 neurons recorded in M1, we found that 18.7% had a high correlation exclusively with hand orientation, 15.9% with movement direction, and 29.5% with both movement direction and hand orientation. The distributions of neurons encoding hand orientation and those encoding movement direction were not uniform but coexisted in the same region. The trajectory of hand rotation was reproduced by the firing patterns of the orientation-related neurons independent of the hand reaching direction. These resultssuggest that hand orientation is an independent component for the control of reaching and grasping activity.
基金Supported by the National Natural Science Foundation of China(No.81660158No.81160118No.81400372)
文摘AIM： To evaluate the differences in the functional connectivity（FC） of the primary visual cortex（V1） between the youth comitant exotropia（CE） patients and health subjects using resting functional magnetic resonance imaging（f MRI） data.METHODS： Totally, 32 CEs（25 males and 7 females） and 32 healthy control subjects（HCs）（25 males and 7 females） were enrolled in the study and underwent the MRI scanning. Two-sample t-test was used to examine differences in FC maps between the CE patients and HCs. RESULTS： The CE patients showed significantly less FC between the left brodmann area（BA17） and left lingual gyrus/cerebellum posterior lobe, right middle occipital gyrus, left precentral gyrus/postcentral gyrus and right inferior parietal lobule/postcentral gyrus. Meanwhile, CE patients showed significantly less FC between right BA17 and right middle occipital gyrus（BA19, 37）.CONCLUSION： Our findings show that CE involves abnormal FC in primary visual cortex in many regions, which may underlie the pathologic mechanism of impaired fusion and stereoscopic vision in CEs.
基金supported by the Open Project of State Key Laboratory of Natural Medicines(SKLNMKF202209)the National Natural Science Foundation of China(Nos:82074110 and 82274193)。
文摘Major depressive disorder(MDD),characterized by anhedonia,loss of motivation,behavioral despair,and cognitive abnormalities[1],stands as the second leading cause of disability worldwide[2]owing to its heightened prevalence,suicide rates,and recurrence[3].Empirical evidence and clinical observations have substantiated the notion that patients with MDD often exhibit compromised auditory perception[4].
基金supported by the grants of National Natural Science Foundation of China(31271158,31421091,and 31422025)the Science and Technology Commission of Shanghai Municipality,China(13PJ1401000)the Young 1000 Plan and the Ministry of Science and Technology of China(2015AA020512)
文摘Several recent studies using either viral or transgenic mouse models have shown different results on whether the activation of parvalbumin-positive（PV~＋）neurons expressing channelrhodopsin-2（ChR2） in the primary visual cortex（V1） improves the orientation-and direction-selectivity of V1 neurons. Although this discrepancy was thoroughly discussed in a follow-up communication, the issue of using different models to express ChR2 in V1 was not mentioned. We found that ChR2 was expressed in retinal ganglion cells（RGCs） and V1 neurons in ChR2fl/~＋; PV-Cre mice. Our results showed that the activation of PV~＋RGCs using white drifting gratings alone significantly decreased the firing rates of V1 neurons and improved their direction-and orientation-selectivity. Longduration activation of PV~＋interneurons in V1 further enhanced the feature-selectivity of V1 neurons in anesthetized mice, confirming the conclusions from previous findings. These results suggest that the activation of both PV~＋RGCs and V1 neurons improves feature-selectivity in mice.
基金supported by the National Natural Science Foundation of China(61735016)the Natural Science Foundation of Zhejiang Province(LR20F050002)+3 种基金the Key R&D Program of Zhejiang Province(2020C03009 and 2021C03001)the Zhejiang Leading Innovation and Entrepreneurship Team(202099144)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057)Fundamental Research Funds for the Central Universities.
文摘Fear memory contextualization is critical for selecting adaptive behavior to survive.Contextual fear conditioning(CFC)is a classical model for elucidating related underlying neuronal circuits.The primary visual cortex(V1)is the primary cortical region for contextual visual inputs,but its role in CFC is poorly understood.Here,our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval,and both CFC learning and extinction increased the turnover rate of axonal boutons in V1.The frequency of neuronal Ca^(2+)activity decreased after CFC learning,while CFC extinction reversed the decrease and raised it to the naïve level.Contrary to control mice,the frequency of neuronal Ca^(2+)activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction,indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca^(2+)activity.These findings reveal a critical role of microglia in neocortical information processing in V1,and suggest potential approaches for cellular-based manipulation of acquired fear memory.
基金supported by the STI 2030-Major Projects 2022ZD0208500(to DY)the National Natural Science Foundation of China,Nos.82072011(to YX),82121003(to DY),82271120(to YS)+2 种基金Sichuan Science and Technology Program,No.2022ZYD0066(to YS)a grant from Chinese Academy of Medical Science,No.2019-12M-5-032(to YS)the Fundamental Research Funds for the Central Universities,No.ZYGX2021YGLH219(to KC)。
文摘Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.
基金supported by the National Natural Science Foundation of China,No.31070758,31271060the Natural Science Foundation of Chongqing in China,No.cstc2013jcyj A10085
文摘Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only ＂see＂ pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex（the implant area） is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine（LSVM） as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern.
基金the Fundamental Research Funds for the Central Universities,No.CDJZR11230002
文摘A better understanding of the neural mechanisms of finger-force regulation can help to explain the relationship between the central nervous system and nerve-muscle force, as well as assist in motor functional rehabilitation and the development robot hand designs. In the present study, 11 healthy volunteers performed a different target force-tracking task, which involved the index finger alone, index and middle finger together, and the combination of four fingers （i.e., index, middle, ring, and little）. The target force trace corresponded to 3 levels of 20% maximal voluntary changes （MVC）, 30% MVC, and 40% MVC in 20 seconds. In the test, an unexpected single 120% motor threshold transcranial magnetic stimulation was applied to the primary motor cortex （M1） during force tracking. Results revealed that peak force changes increased with increasing background force and the number of involved task fingers. These results demonstrate that M1 neural activities correlate with finger-force production, and M1 plays a role in finger-force control. Moreover, different neuronal networks were required for different finger patterns; a complicated task required multi-finger combinations and a complicated neuronal network comprised a large number of neurons.
基金supported by the National Basic Research Development Program of China (2013CB329401)the National Natural Science Foundation of China (91420105, 61105116, 91120013, and 90820301)Shanghai Municipal Committee of Science and Technology (088014158 and 098014026)
文摘In this study,we investigated orientation selectivity in cat primary visual cortex（V1） and its relationship with various parameters.We found a strong correlation between circular variance（CV） and orthogonal-topreferred response ratio（O/P ratio）,and a moderate correlation between tuning width and O/P ratio.Moreover,the suppression far from the peak that accounted for the lower CV in cat V1 cells also contributed to the narrowing of the tuning width of cells.We also studied the dependence of orientation selectivity on the modulation ratio for each cell,which is consistent with robust entrainment of the neuronal response to the phase of the drifting grating stimulus.In conclusion,the CV（global measure） and tuning width（local measure） are significantly correlated with the modulation ratio.
文摘Background:Information about the visual world is processed by an ensemble of cortical visual areas,which follow a hierarchical organization.The primary visual cortex(V1)first receives most of this information through the lateral geniculate nucleus(LGN),before being conveyed to higher-order cortical areas.Aside from this connectional route,there is also a complex network of bilateral connections between areas of the visual cortex and the pulvinar,considered as the largest extrageniculate visual thalamic nucleus.Despite an increasing number of studies on pulvinar,the exact function of this thalamic complex remains unknown.In this study,we investigated the functional impact of the lateral posterior(LP)nucleus,the homologue of the primate pulvinar,on the activity of neurons in the primary visual cortex in mice using optogenetic stimulation.Methods:A channel rhodopsin-2 gene-carrying viral vector(AAV5.CaMKII.hChR2-eYFP.WPRE)was injected into the LP of wild-type(C57BL/6)mice.Extracellular recordings of the activity of V1 neurons were carried out using 16-and 32-channel silicon probes.The stimulation of LP was achieved with light pulses(470 nm,20 pulse trains of 5 ms each at 10 Hz)delivered by a 4-channel optrode,which also recorded the thalamic activity.Visual stimuli consisted on drifting sinewave gratings of varying parameters(direction,contrast,spatial or temporal frequency and size).Results:Our preliminary data shows that LP stimulation performed in conjunction with the visual stimulation decreases the amplitude of neuronal responses up to 50%.To date,results indicate that this inhibitory effect is only observed in neurons in the infragranular layers.The response profiles of V1 neurons to size-increasing stimuli were also affected.Conclusions:These findings suggest that the pulvinar nucleus can exert layer-dependent contextual modulation on the activity of neurons in the mouse primary visual cortex.
文摘Background:The primary visual cortex(V1)is a key component of the visual system that builds some of the first levels of coherent visual representations from sparse visual inputs.While the study of its dynamics has been the focus of many computational models for the past years,there is still relatively few research works that put an emphasis on both synaptic plasticity in V1 and biorealism in the context of learning visual inputs.Here,we present a recurrent spiking neural network that is capable of spike timing dependent plasticity(STDP)and we demonstrate its capacity to discriminate spatio-temporal orientation patterns in noisy natural images.Methods:A two stage model was developed.First,natural images flux(be it videos/gratings/camera)were converted into spikes,using a difference of gaussians(DOG)approach.This transformation approximates the retina-lateral geniculate nucleus(LGN)organization.Secondly,a spiking neural network was build using PyNN simulator,mimicking cortical neurons dynamics and plasticity,as well as V1 topology.This network was then fed with spikes generated by the first model and its ability to build visual representations was assessed using control gratings inputs.Results:The neural network exhibited several interesting properties.After a short period of learning,it was capable of learning multiples orientations and reducing noise in such learned feature,compared to the inputs.These learned features were stable even after increasing the noise in inputs and were found to not only encoding the spatial properties of the input,but also its temporal aspects(i.e.,the time of each grating presentation Conclusions:Our work shows that topological structuring of the cortical neural networks,combined with simple plasticity rules,are sufficient to drive strong learning dynamics of natural images properties.This computational model fits many properties found in the literature and provides some theoritical explanations for the shape of tuning curve of certain layers of V1.Further investigations are now conducted to validate its properties against the neuronal responses of rodents,using identical visual stimuli.
基金the International Cooperation and Exchange of the National Natural Science Foundation of China (31320103914)the General Program of the National Natural Science Foundation of China (31370987)+2 种基金the National Natural Science Foundation of China for Outstanding Young Scholars (81622027)the Beijing Nova Program of China (2016B615)the National Basic Research Development Program of China (2017YFA0106100)
文摘Motor timing is an important part of sensorimotor control. Previous studies have shown that beta oscillations embody the process of temporal perception in explicit timing tasks. In contrast, studies focusing on beta oscillations in implicit timing tasks are lacking. In this study, we set up an implicit motor timing task and found a modulation pattern of beta oscillations with temporal perception during movement preparation. We trained two macaques in a repetitive visually-guided reach-to-grasp task with different holding intervals. Spikes and local field potentials were recorded from microelectrode arrays in the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. We analyzed the association between beta oscillations and temporal interval in fixedduration experiments(500 ms as the Short Group and1500 ms as the Long Group) and random-duration experiments(500 ms to 1500 ms). The results showed that the peak beta frequencies in both experiments ranged from15 Hz to 25 Hz. The beta power was higher during the hold period than the movement(reach and grasp) period.Further, in the fixed-duration experiments, the mean poweras well as the maximum rate of change of beta power in the first 300 ms were higher in the Short Group than in the Long Group when aligned with the Center Hit event. In contrast, in the random-duration experiments, the corresponding values showed no statistical differences among groups. The peak latency of beta power was shorter in the Short Group than in the Long Group in the fixed-duration experiments, while no consistent modulation pattern was found in the random-duration experiments. These results indicate that beta oscillations can modulate with temporal interval in their power mode. The synchronization period of beta power could reflect the cognitive set maintaining working memory of the temporal structure and attention.
基金supported by the Graduate Degree Thesis Innovation Foundation of Central South University, No.2009BSXT050
文摘Nogo-A and Nogo receptor （NgR） expression in the visual cortex following a critical developmental period （postnatal days 20-60） has been previously shown. However, little is known regarding Nogo-A and NgR expression between postnatal day 0 and initiation of the critical period. The present study analyzed Nogo-A and NgR expression at four different time points： postnatal day 0 （P0）, before critical period （P14）, during critical period （P28）, and after critical period （P60）. Results showed significantly increased Nogo-A mRNA and protein expression levels in the visual cortex following birth, and expression levels remained steady between P28 and P60. NgR mRNA or protein expression was dramatically upregulated with age and peaked at P14 or P28, respectively, and maintained high expression to P60. In addition, Nogo-A and NgR expression was analyzed in each visual cortex layer in normal developing rats and rats with monocular deprivation. Monocular deprivation decreased Nogo-A and NgR mRNA and protein expression in the rat visual cortex, in particular in layers Ⅱ-Ⅲ and Ⅳ in the visual cortex contralateral to the deprived eye. These findings suggested that Nogo-A and NgR regulated termination of the critical period in experience- dependent visual cortical plasticity.
基金supported by the National Natural Science Foundation of China(81771210)the Natural Science Foundation of Guangdong Province,China(2015A030313288)。
文摘Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθoscillation recorded during periods when L-dopa is withdrawn(the off L-dopa state).To gain insight into processes underlying this activity,we explored the relationship between primary motor cortex(M1)oscillatory activity and BG output in LID.We recorded local field potentials in the substantia nigra pars reticulata(SNr)and M1 of awake,inattentive resting rats before and after L-dopa priming in Sham control,Parkinson disease model,and LID model groups.We found that chronic L-dopa increasedθsynchronization and information flow between the SNr and M1 in off L-dopa state LID rats,with a SNr-to-M1 flow directionality.Compared with the on state,θoscillational activity(θsynchronization and informationflow)during the off state were more closely associated with abnormal involuntary movements.Our findings indicate thatθoscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1θoscillation may participate in the induction of dyskinesia.
基金supported by the National Natural Science Foundation of China,No.82071254(to WZ).
文摘Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia.Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia.Currently,studies have reported increased oscillation power in cases of levodopa-induced dyskinesia.However,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia.Furthermore,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is unclear.We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease.Furthermore,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma flow.Administration of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum flow.However,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum direction.These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
