Morphological disruption and visual tuning alterations in the primary visual cortex in glaucoma(DBA/2J)mice

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.

Age-related Changes of Glu/GABA Expression in the Primary Visual Cortex of Cat

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.

Age and Sex-related Dendritic Changes in the Visual Cortex of the Rat

Visual functions undergo an age-related degradation. However, the neural mechanisms underlying these changes are not yet clear. This study was designed to investigate the influence of age and sex on the anatomy of the rat＇s visual cortex. Dendritic tree extent and spine density were examined in young adult rats （2-3 months） and aged male and female rats （22-24 months） using a modified Golgi-Cox staining method. A sex difference in dendritic branching of the pyramidal cells was found among young adults. However, this difference disappeared during aging, due to a reduction in branching with age for males but not for females. Moreover, the pyramidal cells of young males also have a greater spine density. Although there was a reduction in spine density with age for both sexes, this reduction was more pronounced for males, resulting in a disappearance of sex difference with age. Thus these results suggest that aging could lead to the degeneration of dendrites, which might contribute to the degradation of age-related visual functions. Also the results indicate that age-related degeneration of dendrites is more severe for males than for females.

Altered intrinsic functional connectivity of the primary visual cortex in youth patients with comitant exotropia: a resting state fMRI study

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.

Postnatal development of NADPH-diaphorase expression in the visual cortex of the golden hamster

Nitric oxide is an important neuromodulator in the brain and is involved in the development of visual system. But it is not clear how nitric oxide and nitric oxide synthase （NOS） are involved in the developing visual cortex of rodents. Thus we examined the expression of NOS activity in the postnatal developing visual cortex of the golden hamster by using histochemical technique for NADPH-diaphorase （NADPH-d）. A heavily stained NADPH-d band was observed in the neuropil of the visual cortex. This NADPH-d band initially appeared in the cortical plate from the day of birth （P0） to postnatal day 4 （P4）. From P7 to P21, this band was confined to area 17 and migrated to the deeper layers Ill IV and V VI before it eventually disappeared at P28. Such developmental trends of the band correlated well with the process of formation and establishment of the geniculo-cortical projection patterns. Thus, the areal specific development of the band suggests that NOS is closely related to the cortical differentiation and synaptic formation of the primary visual cortex. On the other hand, monocular eye enucleation on P1 could not alter the appearance of this NADPH-d positive band, indicating a non-activity dependant role of NOS. In addition, differences in the laminar distributions and developmental sequence between the heavily and lightly stained NADPH-d positive neurons during development suggest that they play different roles in the development.

Frequency spectrum might act as communication code between retina and visual cortex Ⅰ

AIM: To explore changes and possible communication relationship of local potential signals recorded simultaneously from retina and visual cortex I(V1).·METHODS: Fourteen C57BL/6J mice were measured with pattern electroretinogram(PERG) and pattern visually evoked potential(PVEP) and fast Fourier transform has been used to analyze the frequency components of those signals.· RESULTS: The amplitude of PERG and PVEP was measured at about 36.7 μV and 112.5 μV respectively and the dominant frequency of PERG and PVEP, however,stay unchanged and both signals do not have second, or otherwise, harmonic generation.· CONCLUSION: The results suggested that retina encodes visual information in the way of frequency spectrum and then transfers it to primary visual cortex.The primary visual cortex accepts and deciphers the input visual information coded from retina. Frequency spectrum may act as communication code between retina and V1.

Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

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.

Experience-dependent expression of Nogo-A and Nogo receptor in the developing rat visual cortex

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.

Binocular form deprivation influences the visual cortex

a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are considered to play a crucial role in synaptic plasticity in the developing visual cortex. In this study, we established a rat model of binocular form deprivation by suturing the rat binocular eyelids before eye-opening at postnatal day 14. During development, the decay time of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors of normal rats became longer after eye- opening; however, the decay time did not change significantly in binocular form deprivation rats. The peak value in the normal group became gradually larger with age, but there was no significant change in the binocular form deprivation group. These findings indicate that binocular form deprivation influences the properties of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat visual cortex around the end of the critical period, indicating that form stimulation is associated with the experience-dependent modification of neuronal synapses in the visual cortex.

Functional magnetic resonance imaging evaluation of visual cortex activation in patients with anterior visual pathway lesions

The aim of this study was to examine the secondary visual cortex functional disorder in patients with glaucoma and large pituitary adenoma by functional magnetic resonance imaging, and to determine the correlation between visual field defect and primary visual cortex activation. Results showed that single eye stimulation resulted in bilateral visual cortex activation in patients with glaucoma or large pituitary adenoma. Compared with the normal control group, the extent and intensity of visual cortex activation was decreased after left and right eye stimulation, and functional magnetic resonance imaging revealed a correlation between visual field defects and visual cortex activation in patients with glaucoma and large pituitary adenoma. These functional magnetic resonance imaging data suggest that anterior optic pathway lesions can cause secondary functional disorder of the visual cortex, and that visual defects are correlated with visual cortex activation.

Levodopa methyl ester increases nerve growth factor expression in visual cortex area 17 in a feline model of strabismic amblyopia

In the present study, a feline model of strabismic amblyopia was established during a sensitive developmental period, and the influence of levodopa methyl ester and levodopa on nerve growth factor expression in the visual cortex （area 17） was compared. Pattern visual-evoked potential and immunohistochemistry results showed that levodopa methyl ester and levodopa treatment shortened P10o wave latency, increased Pleo amplitude, and increased the number of endogenous nerve growth factor-positive cells in visual cortex levels. In particular, the effects of levodopa methyl ester were superior to levodopa treatment.

Neuroregeneration in the visual cortex

Totally three articles focusing on “the expression of Nogo-A, Nogo receptor and NADPH-diaphorase in the developing rat visual cortex and the effects of levodopa methyl ester on nerve growth factor expression in visual cortex area 17 in strabismic amblyopia” are published in three issues. We hope that our readers find these papers useful to their research.

AB072.Functional impact of the lateral posterior nucleus on the mouse primary visual cortex

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.

AB009.Learning dynamics in a neural network model of the primary visual cortex

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.

AB059.Expression patterns of CB1R,NAPE-PLD,and FAAH in the primary visual cortex of vervet monkeys

Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN).Few data are available on cortical recipients’structures of the dLGN,namely the primary visual cortex(V1).The goal of this study is to characterize the expression and localization of the metabotropic cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1.Methods:Using Western blots and immunohistochemistry,we investigated the expression patterns of CB1R,NAPE-PLD,and FAAH in the vervet monkey primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in the primary visual cortex throughout the rostro-caudal axis.CB1R showed very low levels of staining in cortical layer 4,with higher expressions in all other cortical layers,especially layer 1.NAPE-PLD and FAAH expressions were highest in layers 1,2 and 3,and lowest in layer 4.Conclusions:Interestingly enough,CB1R was very low in layer 4 of V1 in comparison to the other cortical layers.The visual information coming from the dLGN and entering layer 4Calpha(magno cells)and 4Cbeta(parvo cells)may be therefore modulated by the higher expression levels of CB1R in cortical layers 2 and 3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in the outer cortical layers.These data indicate that CB1R system can influence the network of activity patterns in the visual stream after the visual information has reached area V1.These novel results provide insights for understanding the role of the endocannabinoids in the modulation of cortical visual inputs,and hence,visual perception.

Study on Long-term Potentiation in Developing Rat Visual Cortex during the Critical Period of Plasticity

Purpose: To study the property of LTP in layers Ⅱ～Ⅳof the rats visual cortex at different postnatal days induced by pairing low-frequency stimulation at layer Ⅳ with post synaptic depolarization in order to explore the synaptic and cellular mechanism of experience-dependent plasticity in the visual cortex.Methods: Postsynaptic currents (PSCs) of layers Ⅱ～Ⅳ in visual cortex slices of Wistar rats aged P0-29 d were recorded by patch-clamp whole cell recording method. Long-term potentiation (LTP) was induced by low-frequency stimulation (LFS) at 1Hz for 60～90 s.Each pulse of the LFS paired with depolarization of post-synaptic neurons to -20 mV.100μM APV, a kind of competitive N-methyl-d-aspartate (NMDA) receptor antagonist, was both applied to some slices to test the property of LTP.Results: 1. The LTP incidence was very low before P10d (5/34), and increased rapidly to the top at P15-24 d (17/28), then decreased sharply to 1/5 at P25-29 d, coinciding well with the critical period of plasticity of rat visual cortex. The LTP incidence of P15-29d (after eye opening, 18/33) was significantly higher than that of P0-14 d (before eye opening, 12/43, P ＜ 0.05). 2. Compared with non-APV applied group (30/76), LTP incidence of APV applied group (4/33) was significantly decreased (P ＜ 0.01 ). There were 4 Ⅳ-Ⅳ horizontal synapses. APV application could not block the LTP induction.Conclusions: 1. LTP was a reflection of naturally occurring, experience-dependent plasticity in rat visual cortex. The patterned visual stimuli received after eye opening might be an activation factor of the synaptic plasticity. 2. LTP of visual cortex induced by LFS in layer Ⅳ paired with postsynaptic depolarization was NMDA receptor dependent during the critical period of visual plasticity. However, there were LTP existed in Ⅳ-Ⅳ horizontal synapses which could not be blocked by 100μM APV.

Detection of the movement direction by the cells with directional receptive fields in the primary visual cortex of the cat

The study was performed on neurons with direction selective (DS) receptive fields (RFs) in the primary visual cortex of the cat. Preferred directions (PDs) of these cells to a single light spot and a system of two identical light spots moving across the RF with a given angle between them were compared. Directional interactions appeared when the angles between the directions of the two moving spots were 30o or 60o. PD for 56% of the cells coincided with bisectors of these angles. These cells responded to a combination of the two moving stimuli as if only one stimulus moved in the RF in an intermediate direction. This direction coincided with PD of the DS neuron to a single spot. Also, the investigation revealed that DS neurons responded to stimuli moving at such angles as 180o (to preferred and opposite directions simultaneously). In the further experiment we investigated responses of the DS cells in the primary visual cortex of RF. The angle between the directions of the two moving spots was 60o. These cells responded to a combination of the two moving stimuli as if only one stimulus moved in RF in an intermediate direction. The more relative luminance of one of spots in pair was, the closer the intermediate direction approached to the direction of this spot).

Local field potentials,spiking activity,and receptive fields in human visual cortex

The concept of receptive field(RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals,while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials(LFPs) and spiking activity in human visual cortex(V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from lowfrequency activity(LFA, 0.5–30 Hz) were larger than those estimated from low-gamma activity(LGA, 30–60 Hz) and high-gamma activity(HGA, 60–150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing.

A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges

Major depressive disorder(MDD)is a highly heterogeneous mental disorder,and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease.Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients,and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex.In this review,we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression.In addition,we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD.Although the precise roles of visual cortex abnormalities in MDD remain uncertain,this undervalued brain region may become a novel area for the treatment of depressed patients.

Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice

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.