An egalitarian network model for the emergence of simple and complex cells in visual cortex

We explain how simple and complex cells arise in a large-scale neuronal network model of the primary visual cortex of the macaque. Our model consists of approximately 4000 integrate-and-fire, conductance-based point neurons, representing the cells in a small, 1-mm(2) patch of an input layer of the primary visual cortex. In the model the local connections are isotropic and nonspecific, and convergent input from the lateral geniculate nucleus confers cortical cells with orientation and spatial phase preference. The balance between lateral connections and lateral geniculate nucleus drive determines whether individual neurons in this recurrent circuit are simple or complex. The model reproduces qualitatively the experimentally observed distributions of both extracellular and intracellular measures of simple and complex response.     

Selective expression of m2 muscarinic receptor in the parvocellular channel of the primate visual cortex.

Visual information in primates is relayed from the dorsal lateral geniculate nucleus to the cerebral cortex by three parallel neuronal channels designated the parvocellular, magnocellular, and interlaminar pathways. Here we report that m2 muscarinic acetylcholine receptor in the macaque monkey visual cortex is selectively associated with synaptic circuits subserving the function of only one of these channels. The m2 receptor protein is enriched both in layer IV axons originating from parvocellular layers of the dorsal lateral geniculate nucleus and in cytochrome oxidase poor interblob compartments in layers II and III, which are linked with the parvocellular pathway. In these compartments, m2 receptors appear to be heteroreceptors, i.e., they are associated predominantly with asymmetric, noncholinergic synapses, suggesting a selective role in the modulation of excitatory neurotransmission through the parvocellular visual channel.     

Glial cells develop a laminar pattern before neuronal cells in the lateral geniculate nucleus.

The lateral geniculate nucleus, which lies between the retina and the striate cortex in the visual pathway of mammals, is often made up of several distinctive cell layers, or laminae. We have used immunohistochemical methods to localize two glial cell intermediate filament proteins, glial fibrillary acidic protein and vimentin, and have found that layering of glial cells is evident before neuronal cell layers develop in the lateral geniculate nucleus. The correlation between glial cell lamination and neuronal lamination is consistent with the suggestion that glia are guiding neurons not only during the early postmitotic migratory phase of development but also during the later formation of functional divisions such as layers and nuclei.     

Brainstem control of response modes in neurons of the cat''s lateral geniculate nucleus.

The visual pathway from retina through the lateral geniculate nucleus to visual cortex in the cat is comprised of several parallel neuronal streams that independently analyze different aspects of the visual scene. The best known of these are the X and Y pathways that relay through the geniculate A laminae. Recent receptive-field studies of retinal and geniculate neurons suggest that there is a further elaboration of cell types at the level of the lateral geniculate nucleus. That is, two types of geniculate X cells with different temporal patterns of responses to visual stimuli are recognized, one with "nonlagged" features, exhibiting shorter response latencies and another with "lagged" features; all retinal X cells are nonlagged. We asked whether nonlagged and lagged responses represent different cell classes or two response modes of the same cells, perhaps under the control of nonretinal afferents to these relay cells. Accordingly, we studied the effects on appropriate receptive-field properties of electrical activation of the midbrain parabrachial region, which is a major nonretinal input to relay cells. Such parabrachial stimulation made each of the eight lagged X cells much more like nonlagged cells, and this stimulation completely transformed the lagged response profiles of six of the eight cells to nonlagged. We thus conclude that the property of lagged responsiveness, which is an emergent property of the lateral geniculate nucleus, is a different response mode of the same cells that can also display nonlagged responses, rather than representing different cell classes; furthermore, this switching between response modes is, at least partly, under the control of afferents from the parabrachial region.     

N-methyl-D-aspartate receptors contribute to excitatory postsynaptic potentials of cat lateral geniculate neurons recorded in thalamic slices.

Neurons of the cat's dorsal lateral geniculate nucleus were recorded intracellularly to study the contribution of N-methyl-D-aspartate (NMDA) receptors to excitatory postsynaptic potentials (EPSPs) and low-threshold calcium spikes. EPSPs were evoked by stimulation of retinogeniculate axons in the optic tract and/or corticogeniculate axons in the optic radiations; EPSPs from both sources were similar. These EPSPs had one or two components, and the second component had several characteristics of NMDA receptor-mediated events. For example, EPSP amplitude decreased when neurons were hyperpolarized and increased when stimulus frequency was increased; these EPSPs could also be blocked reversibly by application of the selective NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). We also studied the influence of NMDA receptors on low-threshold calcium spikes, which are large, voltage- and calcium-dependent depolarizations that are often accompanied by high-frequency action potential discharge. APV blocked synaptically activated low-threshold calcium spikes, but APV had no effect on low-threshold calcium spikes that were elicited by current injection. Therefore, APV does not appear to have a direct effect on the T-type calcium channel that is involved in generation of low-threshold calcium spikes. The voltage and frequency dependence of the NMDA receptor-mediated component of the EPSPs, as well as its ability to trigger low-threshold calcium spikes, provide for complex signal processing in the lateral geniculate nucleus.     

Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex.

In areas 17 and 18 of the cat visual cortex the firing probability of neurons, in response to the presentation of optimally aligned light bars within their receptive field, oscillates with a peak frequency near 40 Hz. The neuronal firing pattern is tightly correlated with the phase and amplitude of an oscillatory local field potential recorded through the same electrode. The amplitude of the local field-potential oscillations are maximal in response to stimuli that match the orientation and direction preference of the local cluster of neurons. Single and multiunit recordings from the dorsal lateral geniculate nucleus of the thalamus showed no evidence of oscillations of the neuronal firing probability in the range of 20-70 Hz. The results demonstrate that local neuronal populations in the visual cortex engage in stimulus-specific synchronous oscillations resulting from an intracortical mechanism. The oscillatory responses may provide a general mechanism by which activity patterns in spatially separate regions of the cortex are temporally coordinated.     

Relationship between monocularly deprivation and amblyopia rats and visual system development

Objective:To explore the changes of lateral geniculate body and visual cortex in monocular strabismus and form deprived amblyopic rat,and visual development plastic stage and visual plasticity in adult rats.Methods:A total of 60 SD rats ages 13 d were randomly divided into A,B,C three groups with 20 in each group,group A was set as the normal control group without any processing,group B was strabismus amblyopic group,using the unilateral extraocular rectus resection to establish the strabismus amblyopia model,group C was monocular form deprivation amblyopia group using unilateral eyelid edge resection+lid suture.At visual developmental early phase(P2S),meta phase(P3S),late phase(P45)and adult phase(P120),the lateral geniculate body and visual cortex area 17 of five rats in each group were exacted for C-fos Immunocytochemistry.Neuron morphological changes in lateral geniculate body and visual cortex was observed,the positive neurons differences of C-fos expression induced by light stimulation was measured in each group,and the condition of radiation development of P120 amblyopic adult rats was observed.Results:In groups B and C,C-fos positive cells were significantly lower than the control group at P25(P0.05),there was no statistical difference of C-fos protein positive cells between group B and group A(P0.05),C-fos protein positive cells level of group B was significantly lower than that of group A(P0.05).The binoculus C-fos protein positive cells level of groups B and C were significantly higher than that of control group at P35,P4S and P120 with statistically significant differences(P0.05).Conclusions:The increasing of C-fos expression in geniculate body and visual cortex neurons of adult amblyopia suggests the visual cortex neurons exist a certain degree of visual plasticity.     

Prenatal monocular enucleation induces a selective loss of low-spatial-frequency cortical responses to the remaining eye.

During early development, interactions between the two eyes are critical in the formation of eye-specific domains within the lateral geniculate nucleus and the visual cortex. When monocular enucleation is done early in prenatal life, it induces remarkable anatomical and functional reorganizations of the visual pathways. Behavioral data have shown a loss in sensitivity to low-spatial-frequency gratings in cats. To correlate the behavioral observations with a possible change in the analysis of contrast at the level of primary visual areas we recorded visual evoked potentials at the 17/18 border in two cats enucleated prenatally (gestational age at enucleation, 39-42 days), three neonatal, two control animals, and one animal with a surgical removal of Y-ganglion fibers. Our results show a strong attenuation in the amplitude of response at all contrast values for gratings of low spatial frequency in prenatally enucleated cats, whereas neonatally enucleated and control animals present responses of comparable amplitude. We conclude that the behavioral results reflect the reduced sensitivity for low frequencies of visual cortical neurons. In addition, we define a critical period for the development of the contrast-sensitivity function that seems to be limited to the prenatal gestation period. We suggest that the prenatal interruption of binocular interactions leads to a functional elimination of the Y-ganglion system.     

Monoclonal antibodies to nerve growth factor affect the postnatal development of the visual system.

Exogenous supply of nerve growth factor (NGF) prevents the effects of monocular deprivation. This suggests that visual afferents may be competing for an endogenous neurotrophic factor, related to NGF, whose production by postsynaptic cells depends on the activity of afferent fibers. To test the hypothesis that endogenous NGF may play a role in the functional and anatomical development of the rat geniculo cortical system, the physiological action of NGF in the rat visual system was antagonized by using two independent monoclonal antibodies which neutralize NGF (alpha D11 and 4C8). To provide a continuous supply of antibodies during the period of visual cortical plasticity, alpha D11 or 4C8 antibody-producing hybridoma cells were implanted in the lateral ventricle of rats at postnatal day 15. This resulted in dramatic alterations of two of the most important parameters characterizing the functional development of the visual system, namely, visual acuity and binocularity of cortical neurons and in shrinkage of cells in the lateral geniculate nucleus. This demonstrates that the action of endogenous NGF is necessary for the normal functional and anatomical development of the geniculocortical system.     

A neuronal network model of macaque primary visual cortex (V1): orientation selectivity and dynamics in the input layer 4Calpha

In this paper, we offer an explanation for how selectivity for orientation could be produced by a model with circuitry that is based on the anatomy of V1 cortex. It is a network model of layer 4Calpha in macaque primary visual cortex (area V1). The model consists of a large number of integrate-and-fire conductance-based point neurons, both excitatory and inhibitory, which represent dynamics in a small patch of 4Calpha-1 mm(2) in lateral area-which contains four orientation hypercolumns. The physiological properties and coupling architectures of the model are derived from experimental data for layer 4Calpha of macaque. Convergent feed-forward input from many neurons of the lateral geniculate nucleus sets up an orientation preference, in a pinwheel pattern with an orientation preference singularity in the center of the pattern. Recurrent cortical connections cause the network to sharpen its selectivity. The pattern of local lateral connections is taken as isotropic, with the spatial range of monosynaptic excitation exceeding that of inhibition. The model (i) obtains sharpening, diversity in selectivity, and dynamics of orientation selectivity, each in qualitative agreement with experiment; and (ii) predicts more sharpening near orientation preference singularities.     

Slow intrinsic rhythm in the koniocellular visual pathway

Slow rhythmic changes in nerve-cell activity are characteristic of unconscious brain states and also may contribute to waking brain function by coordinating activity between cortical and subcortical structures. Here we show that slow rhythms are exhibited by the koniocellular (K) pathway, one of three visual pathways beginning in the eye and projecting through the lateral geniculate visual relay nucleus to the cerebral cortex. We recorded activity in pairs and ensembles of neurons in the lateral geniculate nucleus of anesthetized marmoset monkeys. We found slow rhythms are common in K cells but are rare in parvocellular and magnocellular cell pairs. The time course of slow K rhythms corresponds to subbeta (<10 Hz) EEG frequencies, and high spike rates in K cells are associated with low power in the theta and delta EEG bands. By contrast, spontaneous activity in the parvocellular and magnocellular pathways is neither synchronized nor strongly linked to EEG state. These observations suggest that parallel visual pathways not only carry different kinds of visual signals but also contribute differentially to brain circuits at the first synapse in the thalamus. Differential contribution of sensory streams to rhythmic brain circuits also raises the possibility that sensory stimuli can be tailored to modify brain rhythms.     

Statistics of lateral geniculate nucleus (LGN) activity determine the segregation of ON/OFF subfields for simple cells in visual cortex

The receptive fields for simple cells in visual cortex show a strong preference for edges of a particular orientation and display adjacent excitatory and inhibitory subfields. These subfields are projections from ON-center and OFF-center lateral geniculate nucleus cells, respectively. Here we present a single-cell model using ON and OFF channels, a natural scene environment, and synaptic modification according to the Bienenstock, Cooper, and Munro (BCM) theory. Our results indicate that lateral geniculate nucleus cells must act predominantly in the linear region around the level of spontaneous activity, to lead to the observed segregation of ON/OFF subfields.     

Theory of orientation tuning in visual cortex.

The role of intrinsic cortical connections in processing sensory input and in generating behavioral output is poorly understood. We have examined this issue in the context of the tuning of neuronal responses in cortex to the orientation of a visual stimulus. We analytically study a simple network model that incorporates both orientation-selective input from the lateral geniculate nucleus and orientation-specific cortical interactions. Depending on the model parameters, the network exhibits orientation selectivity that originates from within the cortex, by a symmetry-breaking mechanism. In this case, the width of the orientation tuning can be sharp even if the lateral geniculate nucleus inputs are only weakly anisotropic. By using our model, several experimental consequences of this cortical mechanism of orientation tuning are derived. The tuning width is relatively independent of the contrast and angular anisotropy of the visual stimulus. The transient population response to changing of the stimulus orientation exhibits a slow "virtual rotation." Neuronal cross-correlations exhibit long time tails, the sign of which depends on the preferred orientations of the cells and the stimulus orientation.     

Mexican hats and pinwheels in visual cortex

Many models of cortical function assume that local lateral connections are specific with respect to the preferred features of the interacting cells and that they are organized in a Mexican-hat pattern with strong "center" excitation flanked by strong "surround" inhibition. However, anatomical data on primary visual cortex indicate that the local connections are isotropic and that inhibition has a shorter range than excitation. We address this issue in an analytical study of a neuronal network model of the local cortical circuit in primary visual cortex. In the model, the orientation columns specified by the convergent lateral geniculate nucleus inputs are arranged in a pinwheel architecture, whereas cortical connections are isotropic. We obtain a trade-off between the spatial range of inhibition and its time constant. If inhibition is fast, the network can operate in a Mexican-hat pattern with isotropic connections even with a spatially narrow inhibition. If inhibition is not fast, Mexican-hat operation requires a spatially broad inhibition. The Mexican-hat operation can generate a sharp orientation tuning, which is largely independent of the distance of the cell from the pinwheel center.     

Evolution of GABAergic circuitry in the mammalian medial geniculate body.

Many features in the mammalian sensory thalamus, such as the types of neurons, their connections, or their neurotransmitters, are conserved in evolution. We found a wide range in the proportion of gamma-aminobutyric acidergic (GABAergic) neurons in the medial geniculate body, from <1% (bat and rat) to 25% or more (cat and monkey). In the bat, some medial geniculate body subdivisions have no GABAergic cells. Species-specific variation also occurs in the somesthetic ventrobasal complex. In contrast, the lateral geniculate body of the visual system has about the same proportion of GABAergic cells in many species. In the central auditory pathway, only the medial geniculate body shows this arrangement; the relative number of GABAergic cells in the inferior colliculus and auditory cortex is similar in each species. The range in the proportion of GABAergic neurons suggests that there are comparative differences in the neural circuitry for thalamic inhibition. We conclude that the number of GABAergic neurons in thalamic sensory nuclei may have evolved independently or divergently in phylogeny. Perhaps these adaptations reflect neurobehavioral requirements for more complex, less stereotyped processing, as in speech-like communication.     

A model of ocular dominance column development by competition for trophic factor

Recent experimental evidence has shown that application of certain neurotrophic factors (NTs) to the developing primary visual cortex prevents the development of ocular dominance (OD) columns. One interpretation of this result is that afferents from the lateral geniculate nucleus compete for postsynaptic trophic factor in an activity-dependent manner. Application of excess trophic factor eliminates this competition, thereby preventing OD column formation. We present a model of OD column development, incorporating Hebbian synaptic modification and activity-driven competition for NT, which accounts for both normal OD column development as well as the prevention of that development when competition is removed. In the “control” situation, when available NT is below a critical amount, OD columns form normally. These columns form without weight normalization procedures and in the presence of positive inter-eye correlations. In the “experimental” case, OD column development is prevented in a local neighborhood in which excess NT has been added. Our model proposes a biologically plausible mechanism for competition between neural populations that is motivated by several pieces of experimental data, thereby accounting for both normal and experimentally perturbed conditions.     

The spatial receptive field of thalamic inputs to single cortical simple cells revealed by the interaction of visual and electrical stimulation

Electrical stimulation of the thalamus has been widely used to test for the existence of monosynaptic input to cortical neurons, typically with stimulation currents that evoke cortical spikes with high probability. We stimulated the lateral geniculate nucleus (LGN) of the thalamus and recorded monosynaptically evoked spikes from layer 4 neurons in visual cortex. We found that with moderate currents, cortical spikes were evoked with low to moderate probability and their occurrence was modulated by ongoing sensory (visual) input. Furthermore, when repeated at 8-12 Hz, electrical stimulation of the thalamic afferents caused such profound inhibition that cortical spiking activity was suppressed, aside from electrically evoked monosynaptic spikes. Visual input to layer 4 cortical cells between electrical stimuli must therefore have derived exclusively from LGN afferents. We used white-noise visual stimuli to make a 2D map of the receptive field of each cortical simple cell during repetitive electrical stimulation in the LGN. The receptive field of electrically evoked monosynaptic spikes (and thus of the thalamic input alone) was significantly elongated. Its primary subfield was comparable to that of the control receptive field, but secondary (flanking) subfields were weaker. These findings extend previous results from intracellular recordings, but also demonstrate the effectiveness of an extracellular method of measuring subthreshold afferent input to cortex.     

Blockade of action potential activity alters initial arborization of thalamic axons within cortical layer 4.

In the formation of connections during the development of the nervous system, it is generally accepted that there is an early phase not requiring neural activity and a later activity-dependent phase. The initial processes of axonal pathfinding and target selection are not thought to require neural activity, whereas the later fine-tuning of connections into their final adult patterns does. We report an apparent exception to this rule in which action potential activity seems to be required very early in development for thalamic axons to form appropriate patterns of terminal arborizations with their ultimate target neurons in layer 4 of the cerebral cortex. Blockade of sodium action potentials during the 2-week fetal period when visual thalamic axons initially grow into the primary visual cortex in cats prevents the normally occurring branching of lateral geniculate nucleus axons within layer 4. This observation implies a role for action-potential activity in cerebral cortical development far earlier than previously suspected, weeks before eye-opening and the onset of the well-known process of activity-dependent reorganization of axonal terminal arbors that leads to the formation of ocular dominance columns.     

Mean-field theory of a neural network.

A single-cell theory for the development of selectivity and ocular dominance in visual cortex has been generalized to incorporate more realistic neural networks that approximate the actual anatomy of small regions of cortex. In particular, we have analyzed a network consisting of excitatory and inhibitory cells, both of which may receive information from the lateral geniculate nucleus (LGN) and then interact through cortico-cortical synapses in a mean-field approximation. Our investigation of the evolution of a cell in this mean-field network indicates that many of the results on existence and stability of fixed points that have been obtained previously in the single-cell theory can be successfully generalized here. We can, in addition, make explicit further statements concerning the independent effects of excitatory and inhibitory neurons on selectivity and ocular dominance. For example, shutting off inhibitory cells lessens selectivity and alters ocular dominance (masked synapses). These inhibitory cells may be selective, but there is no theoretical necessity that they be so. Further, the intercortical inhibitory synapses do not have to be very responsive to visual experience. Most of the learning process can occur among the excitatory LGN-cortical synapses.     

Synapse-to-Neuron Ratio in the Lateral Geniculate Nucleus of Rats Exposed Chronically to Ethanol

Effects of chronic ethanol exposure on synapse-to-neuron ratio in the rat lateral geniculate nucleus were investigated. Male Sprague-Dawley rats were exposed to ethanol, using the Lieber-DeCarli liquid diets, for 4 months starting at the age of 5 weeks. Brains were per-fusion-fixed, and the region containing the dorsal lateral geniculate nucleus was cut into slabs (500 μm thick) that were epoxy resin-embedded. From each rat, three slabs containing the structure were serially sectioned for electron microscopy. Using the double disector method, the study shows an unaltered synapse-to-neuron ratio in ethanol-treated rats when compared with controls. The findings are in agreement with previous studies on the visual system using the seme exposure model. In contrast, a previous study has shown that the synapse-to-neuron ratio in locus ceruleus of ethanol-treated rats is reduced by 50%. Other studies have shown that, whereas the glutamatergic NMDA receptor is very sensitive to ethanol, the kainate/AMPA type of receptor is very much less so. Thus, the difference in ethanol-induced synapse elimination between the two regions may reflect this different sensitivity of the glutamatergic receptors, which are of the kainate/AMPA type in the lateral geniculate nucleus and of the NMDA type in the locus ceruleus.