Neurons In Cat Visual Cortex Research Articles

Gamma-Rhythmic Input Causes Spike Output

The gamma rhythm has been implicated in neuronal communication, but causal evidence remains indirect. We measured spike output of local neuronal networks and emulated their synaptic input through optogenetics. Opsins provide currents through somato-dendritic membranes, similar to synapses, yet under experimental control with high temporal precision. We expressed Channelrhodopsin‑2 in excitatory neurons of cat visual cortex and recorded neuronal responses to light with different temporal characteristics. Sine waves of different frequencies entrained neuronal responses with a reliability that peaked for input frequencies in the gamma band. Crucially, we also presented white-noise sequences, because their temporal unpredictability enables analysis of causality. Neuronal spike output was caused specifically by the input’s gamma component. This gamma-specific transfer function is likely an emergent property of in‑vivo networks with feedback inhibition. The method described here could reveal the transfer function between the input to any one and the output of any other neuronal group.

Robust Discovery of Temporal Structure in Multi-neuron Recordings Using Hopfield Networks

Abstract We present here a novel method for the classical task of extracting reoccurring spatiotemporal patterns from spiking activity of large populations of neurons. In contrast to previous studies that mainly focus on synchrony detection or exactly recurring binary patterns, we perform the search in an approximate way that clusters together nearby, noisy network states in the data. Our approach is to use minimum probability flow (MPF) parameter estimation to determinis- tically fit very large Hopfield networks on windowed spike trains obtained from recordings of spontaneous activity of neurons in cat visual cortex. Examining the structure of the network memories over the spiking activity after training, we find that the networks robustly discover long-range temporal correlations. Specifically, the recurrent network dynamics denoise and group together windowed spike patterns, revealing underlying structure such as cell assemblies. We first demonstrate this by computing an analogy to spike triggered averages that we call memory triggered averages (MTAs). MTAs are obtained by averaging raw spike train windows that converge under the network dynamics to the same memory. The MTAs reveal promi- nent repeating patterns in the data that are difficult to detect with standard methods such as PCA. Additionally, when memories are collected over eight disjoint epochs in 280 seconds of windowed spiking activity from 50 neurons, their counts are nearly identical and the networks store significantly more memories than would be possible if trained on random patterns.

Effects of ketamine and urethane on stimulation-induced c-fos expression in neurons of cat visual cortex

The effects of ketamine and urethane on neuronal activities remain in debate. As a member of immediate early genes family, the expression of c-fos is stimulation dependent and could be treated as an index to evaluate the strength of neural activities. In this study, SABC immunohistochemical techniques were applied to compare the c-fos expression in neurons of the primary visual cortex (V1) of cats and therefore, to evaluate the effects of acute anesthesia with ketamine HCl and uethane on inhibiting neural activities. Our results showed that compared with control cats, there were no significant differences with the average densities of Nissl-stained V1 neurons in each cortical layers of either urethane or ketamine anesthetized cats. In urethane anesthetized cats, neither the average densities nor the immunoreactive intensities of c-fos positive V1 neurons showed significant difference with that of control ones. However, both the average densities and immunoreactive intensities of c-fos positive V1 neurons in ketamine anesthetized cats decreased significantly compared with that of control and urethane anesthetized cats. These results suggested that ketamine has strong inhibitory effects on the activities of visual cortical neurons, whereas urethane did not.

Synchronization Mechanisms in Local Neural Networks in the Neocortex. Modeling and Experimental Studies

Measures of excitation and inhibition were studied in cat visual cortex neurons and the time parameters of epileptiform activity were studied in rat sensorimotor cortex neurons. The results were used to construct a simulation model of a neural network in the Neiroimitator program, and this was used to investigate synchronization mechanisms. The neural network consisted of 30 neurons with different excitation and inhibition time parameters. Studies were performed with the neural network simulation in two states. In the first case, the activity of each neuron was spontaneous, while the second used cycles of excitation and inhibition. Synchronization (simultaneous neuron activity) with the ordered temporal structure (excitation-inhibition cycles, which started simultaneously) was significantly greater than in conditions of spontaneous activity and when cycles started non-simultaneously. These results show that synchronization in local neural networks is increased mainly because of transient inhibition and that the greater amplitude of the summed (field) potential may reflect the synchronous operation of nervous system elements which are not directly connected to each other.

Large-scale model of mammalian thalamocortical systems

The understanding of the structural and dynamic complexity of mammalian brains is greatly facilitated by computer simulations. We present here a detailed large-scale thalamocortical model based on experimental measures in several mammalian species. The model spans three anatomical scales. (i) It is based on global (white-matter) thalamocortical anatomy obtained by means of diffusion tensor imaging (DTI) of a human brain. (ii) It includes multiple thalamic nuclei and six-layered cortical microcircuitry based on in vitro labeling and three-dimensional reconstruction of single neurons of cat visual cortex. (iii) It has 22 basic types of neurons with appropriate laminar distribution of their branching dendritic trees. The model simulates one million multicompartmental spiking neurons calibrated to reproduce known types of responses recorded in vitro in rats. It has almost half a billion synapses with appropriate receptor kinetics, short-term plasticity, and long-term dendritic spike-timing-dependent synaptic plasticity (dendritic STDP). The model exhibits behavioral regimes of normal brain activity that were not explicitly built-in but emerged spontaneously as the result of interactions among anatomical and dynamic processes. We describe spontaneous activity, sensitivity to changes in individual neurons, emergence of waves and rhythms, and functional connectivity on different scales.

Encoding of stimulus movement parameters in the cat visual system

Analysis of matrixes consisting of the numbers of spikes evoked by the movement of simple and complex stimuli in cat visual cortex neurons by the principal components method demonstrated vector encoding. The responses of direction detectors to the movement of points and orientation detectors to changes in the angle of a line were encoded independently in areas V1 and V2 of the cortex. Each type of detector was represented by excitation of two cardinal neurons generating sine and cosine functions. The responses of neurons in the associative cortex with selectivity for the direction of movement of specifically oriented bars depended on four cardinal neurons formed by summation of the excitations of the cardinal neurons of the directional and orientational channels.

Distribution and morphological characterization of phosphate-activated glutaminase-immunoreactive neurons in cat visual cortex

Phosphate-activated glutaminase (PAG) is the major enzyme involved in the synthesis of the excitatory neurotransmitter glutamate in cortical neurons of the mammalian cerebral cortex. In this study, the distribution and morphology of glutamatergic neurons in cat visual cortex was monitored through immunocytochemistry for PAG. We first determined the specificity of the anti-rat brain PAG polyclonal antibody for cat brain PAG. We then examined the laminar expression profile and the phenotype of PAG-immunopositive neurons in area 17 and 18 of cat visual cortex. Neuronal cell bodies with moderate to intense PAG immunoreactivity were distributed throughout cortical layers II–VI and near the border with the white matter of both visual areas. The largest and most intensely labeled cells were mainly restricted to cortical layers III and V. Careful examination of the typology of PAG-immunoreactive cells based on the size and shape of the cell body together with the dendritic pattern indicated that the vast majority of these cells were pyramidal neurons. However, PAG immunoreactivity was also observed in a paucity of non-pyramidal neurons in cortical layers IV and VI of both visual areas. To further characterize the PAG-immunopositive neuronal population we performed double-stainings between PAG and three calcium-binding proteins, parvalbumin, calbindin and calretinin, to determine whether GABAergic non-pyramidal cells can express PAG, and neurofilament protein, a marker for a subset of pyramidal neurons in mammalian neocortex. We here present PAG as a neurochemical marker to map excitatory cortical neurons that use the amino acid glutamate as their neurotransmitter in cat visual cortex.

A novel mechanism of response selectivity of neurons in cat visual cortex.

The spiking of cortical neurons critically depends on properties of the afferent stimuli. In the visual cortex, neurons respond selectively to the orientation and direction of movement of an object. The orientation and direction selectivity is improved upon transformation of the membrane potential changes into trains of action potentials. To address the question of whether the transformation of the membrane potential changes into spiking of a cell depends on the stimulus orientation and the direction of movement, we made intracellular recordings from the cat visual cortex in vivo during presentation of moving gratings of different orientations. We found that the relationship between the membrane polarization and the firing rate (input-output transfer function) depended on the stimulus orientation. The input-output transfer function was steepest during responses to the optimal stimulus; membrane depolarization of a given amplitude led to generation of more action potentials when evoked by an optimal stimulus than during non-optimal stimulation. The threshold for the action potential generation did not depend on stimulus orientation, and thus could not account for the observed difference in the transfer function. Oscillations of the membrane potential in the gamma-frequency range (25-70 Hz) were most pronounced during optimal stimulation and their strength changed in parallel with the changes in the transfer function, suggesting a possible relationship between the two parameters. We suggest that the improved input-output relationship of neurons during optimal stimulation represents a novel mechanism that may contribute to the final sharp orientation selectivity of spike responses in the cortical cells.

The contribution of intracortical inhibition to dynamics of orientation tuning in cat striate cortex neurons

Orientation tuning of some neurons in cat visual cortex (area 17) revealed successive shifts of the preferred orientation and widening of tuning in time during the first 150 ms after onset of a flashing light bar. The mechanisms of these dynamics and the possible role of intracortical inhibition are still under discussion. In this study we analysed the dynamics using the time slice method before and during blockade of GABAergic inhibition by microiontophoretic application of bicuculline and observed two main types of neuronal behaviour. The first group of neurons (39 of 68 units or 57.4%) with relatively sharp tuning and absence or relatively small shifts of preferred orientation under control conditions increased or developed this shift during bicuculline application. Changes in tuning were observed between 30 and 150 ms after stimulus onset when inhibition was blocked. Neurons of the second group (29 units or 42.6% of cases) displayed pronounced shifts of preferred orientation under control conditions which was typically diminished or lost during blockade of inhibition. The results indicate different contributions of intracortical inhibition to different neurons distinguishing by stability or time dependence of their orientation preference during normal response generation. In one group of striate cells orientation tuning was kept narrow and constant in time by intracortical inhibition, while in another group orientation tuning dynamics are induced by inhibitory mechanisms.

Immunocytochemical Localization of Calcium-binding Protein Calretinin Containing Neurons in Cat Visual Cortex

Immunocytochemical Localization of Calcium-binding Protein Calretinin Containing Neurons in Cat Visual Cortex

Massive Autaptic Self-Innervation of GABAergic Neurons in Cat Visual Cortex

Autapses are transmitter release sites made by the axon of a neuron on its own dendrites. We determined the numbers and precise subcellular position of autapses on different spiny and smooth dendritic cell types using intracellular biocytin filling in slices of adult neocortex. Potential self-innervation was light microscopically assessed on 10 pyramidal cells, 7 spiny stellate cells, and 41 smooth dendritic neurons from cortical layers II-V. Putative autapses occurred on each smooth dendritic neuron and on seven pyramids, but not on spiny stellate cells. However, electron microscopic examination of all light microscopically predicted sites on pyramids (n = 28) showed only one case of self-innervation with two autapses on dendritic spines. Interneurons were classified by postsynaptic target distribution () and all putative autapses of seven basket, three dendrite-targeting, and three double bouquet cells were scrutinized. All basket and dendrite-targeting cells established self-innervation, the number of autapses being 12 +/- 7 and 22 +/- 12 (mean +/- SD), respectively; only one of the double bouquet cells formed autapses (n = 3). Basket cell autapses (n = 74) were closer to the soma (12.2 +/- 22.3 microm) than autapses established by dendrite-targeting cells (51.8 +/- 49.9 microm; n = 66). The degree of self-innervation is cell type-specific. Unlike on spiny cells, autapses are abundant on GABAergic basket and dendrite-targeting interneurons, with subcellular location similar to that of synapses formed by the parent cell on other neurons. The extensive self-innervation may modulate integrative properties and/or the firing rhythm of the neuron in a manner temporally correlated with its own activity.

Recurrent excitation in neocortical circuits.

The majority of synapses in the mammalian cortex originate from cortical neurons. Indeed, the largest input to cortical cells comes from neighboring excitatory cells. However, most models of cortical development and processing do not reflect the anatomy and physiology of feedback excitation and are restricted to serial feedforward excitation. This report describes how populations of neurons in cat visual cortex can use excitatory feedback, characterized as an effective "network conductance", to amplify their feedforward input signals and demonstrates how neuronal discharge can be kept proportional to stimulus strength despite strong, recurrent connections that threaten to cause runaway excitation. These principles are incorporated into models of cortical direction and orientation selectivity that emphasize the basic design principles of cortical architectures.

Adaptation aftereffects in single neurons of cat visual cortex: response timing is retarded by adapting.

Extracellular single-unit recordings were made from simple cells in area 17 of anesthetized cats. Cells were tested with drifting gratings under control and adapted conditions. Response amplitude and phase were measured as a function of either contrast or temporal frequency. Adapting not only reduces amplitude, but also retards phase. Adaptation alters the responses of simple cells in a particular way: the onset of the response to each cycle of a sinusoidally modulate stimulus is delayed. Once cells start to respond during each cycle, however, they generally recover to control levels, and the offset of the response is unaffected by adapting. The timing aftereffects are independent of the amplitude aftereffects. Timing aftereffects are tuned around the adapting temporal frequency, with a bias toward lower temporal frequencies. Adaptation thus modifies cortical responses even more specifically then previously thought. Firing rates are depressed primarily at response onset, even after several stimulus cycles have occurred following the end of adapting. Because all cells appear to adapt in this way, the data offer an opportunity to theorize about cortical connectivity. One implication is that inhibition onto a simple cell arises from other simple cells with similar response properties that fire a half-cycle out of phase with the target cell.

Effects of local adaptation of receptive field on sensitivity of the cat visual cortex neurons to cruciform images

The responses to flashing single light bars of different orientation and to cruciform images (CI) were compared in 9 neurons of the cat striate cortex possessing high specific sensitivity to CI, during local adaptation of various receptive field (RF) zones. In most neurons, a two- to threefold reduction in the response to CI with a constantly present bar of optimum or orthogonal orientation, if compared with a response to the figure consisting of two flashing bars, was found. Responses to the CI including an adaptation bar were often increased, if compared with those observed at usual orientation tuning. The role of a cross-orientation inhibition in the formation of a selective sensitivity to CI in the neurons of the visual cortex is discussed.

Map of the synapses formed with the dendrites of spiny stellate neurons of cat visual cortex.

The synaptic input of six spiny stellate neurons in sublamina 4A of cat area 17 was assessed by electron microscopy. The neurons were physiologically characterized and filled with horseradish peroxidase in vivo. After processing the neurons were reconstructed at the light microscopic level using computer-assisted methods and analyzed quantitatively. The extensive branching of the dendritic tree about 50 microns from the soma meant that the distal branches constituted five times the length of proximal dendrite. Proximal and distal portions of a single dendrite from each neuron were examined in series of ultrathin sections (1,456 sections) in the electron microscope. The majority (79%) of the 263 synapses examined were asymmetric; the remainder (21%) were symmetric. Symmetric synapses formed 35% of synapses sampled on proximal dendrites and were usually located on the shaft. They formed only 4% of synapses sampled on distal dendrites. Spines accounted for less than half of the total asymmetric synapses (45%); the remainder were on shafts. Symmetric synapses formed with four of 92 spines. Nine spines formed no synapses. Spiny stellate neurons in cat visual cortex appear to differ considerably from pyramidal neurons in having a significant asymmetric (excitatory) synaptic input to the dendritic shaft.

Synaptic output of physiologically identified spiny stellate neurons in cat visual cortex.

Spiny stellate neurons of area 17 of the cat's visual cortex were physiologically characterised and injected intracellularly with horseradish peroxidase. Six neurons from sublamina 4A were selected. Five had the S-type of simple receptive fields; one had a complex receptive field. Their axons formed boutons mainly in layers 3 and 4. An electron microscopic examination of 45 boutons showed that each bouton formed one asymmetric synapse on average. Spines were the most frequent synaptic target (74%); dendritic shafts formed the remainder (26%). On the basis of ultrastructural characteristics, 8% of the target dendrites were characterised as originating from smooth gamma-aminobutyrate-ergic (GABAergic) neurons. Thus the major output of spiny stellate neurons is to other spiny neurons, probably pyramidal neurons in layer 3 and spiny stellates in layer 4.

Excitation and inhibition in orientation selectivity of cat visual cortex neurons revealed by whole-cell recordings in vivo.

One striking transformation in response properties that occurs in the geniculo-cortical pathway is the appearance of a high degree of orientation selectivity in the cortex. This property may be conceived as arising purely from the excitatory inputs to the cell, as being structured largely by the inhibition a cortical cell receives or could be due to a combination of the two. We have studied the contributions of excitatory and inhibitory inputs to cortical cells' orientation selectivity by analyzing the postsynaptic potentials evoked in cat striate neurones by flashing stimuli of different orientations. We made these recordings using the in vivo whole-cell technique (Xing Pei et al., 1991), which provides more stable and reliable results than classical intracellular recording methods. Our results show that the cat striate cortex exhibits a variety of mechanisms to achieve orientation selectivity. Orientation selectivity of a particular cell can be created by excitatory, by inhibitory, or by a combination of both mechanisms.

Postnatal development and localization of an N-acetylgalactosamine containing glycoconjugate associated with nonpyramidal neurons in cat visual cortex.

We have analyzed the appearance of N-acetylgalactosamine containing glycoconjugates by staining sections of fixed cat visual cortex with the lectins from Vicia villosa (VVA) and Glycine max (SBA) conjugated to fluorescent labels, horseradish peroxidase, or biotin. The appearance of lectin staining during postnatal development followed an inside-out gradient starting in the deep cortical layers at the fourth postnatal week, successively including more of the superficial layers during the first three postnatal months until labelled cells were present throughout layers II-VI at the seventh postnatal month. Staining was associated with the soma and proximal dendrites of bipolar and multipolar nonpyramidal neurons. Outside layer IV large neurons with basket cell and neurogliaform morphology predominated, whereas small multipolar cells were stained in layer IV. High power observation revealed a lattice-like staining on neuronal surfaces. In the cortical white matter staining was found at the nodes of Ranvier. The ultrastructural localization of lectin binding sites was assessed by a pre-embedding histochemical procedure with biotinylated lectin visualized with HRP-conjugated avidin and diaminobenzidine as the chromogen. The reaction product was found exclusively in close association with synaptic terminals on somata and proximal dendrites of nonpyramidal neurons. There was no preference with respect to the morphology of the synaptic structure, i.e., symmetric synapses with ovoid or asymmetric synapses with round vesicles. In the vicinity of synaptic contacts the staining was associated with membranes of astrocytic processes ensheathing the synapses. In the cortical white matter astrocytic processes running along myelinated axons were strongly labelled at the nodes of Ranvier. Comparison of Western blots from 4-week-old and adult cat cortex membranes revealed one lectin-positive protein band with an apparent molecular weight of about 24 kD in conjunction with the histochemical expression of perisynaptic staining in the adult tissue. It is concluded that the employed lectins selectively visualize distal astroglial processes ensheathing synapses on a subpopulation of cortical interneurons and nodes of Ranvier. On the basis of the developmental appearance and localization we consider and discuss the possibility that the N-acetylgalactosamine containing glycoconjugate is involved in the stabilization of synaptic contacts on GABA-ergic interneurons.

Population coding by simultaneous activities of neurons in intrinsic coordinate systems defined by their receptive field weighting functions

In this paper we address the problem of how external stimuli from the outside world, which can be represented as vectors by a set of numbers, might be expressed, transformed, and possibly reconstructed in neuronal networks of sensory brain areas. Our work is based on the approach of modeling the firing rate responses of simple linear sensory neurons. As characteristic functions, the receptive field weighting profiles can be determined from the firing rate responses of linear neurons to external stimuli in electrophysiological experiments. The responses of such neurons to arbitrary stimuli can be described as a linear function of the dot product of the stimulus vector and a special vector, the receptive field weighting function. The stimulus vector can be reconstructed in the coordinate system whose basis vectors are the receptive field weighting functions of linear neurons as a linear combination of the basis vectors and some weighting coefficients calculated from the firing rates of the neurons. Georgopoulos, Kettner, and Schwartz developed a scheme of population coding to reconstruct a simple three-dimensional vector, the direction of an arm movement from results of electrophysiological observations in primate motor cortex. Daugman introduced an iterative algorithm to compress and reconstruct image vectors in a network of neural elements whose receptive field weighting functions were similar to receptive field weighting functions of orientation-selective neurons in cat visual cortex. Pellionisz and Llinas showed in their tensor network theory how sensorimotor transformations of vectors might take place in neuronal networks. We show how these seemingly different approaches are related and compare their advantages and disadvantages. We adopted the iterative algorithm of Daugman to code image vectors and calculated the weights of neural elements taking place in the reconstruction of the stimuli in different layers of the network. Then we determined what the receptive field profiles of neurons in higher layers look like at different stages of the iteration process and at equilibrium. Finally, we provide theoretical predictions that might be verified in electrophysiological experiments to reveal which population coding scheme is applied by the particular neuronal network in sensory areas of the brain.

Organization of suppression in receptive fields of neurons in cat visual cortex.

1. The response to an optimally oriented stimulus of both simple and complex cells in the cat's striate visual cortex (area 17) can be suppressed by the superposition of an orthogonally oriented drifting grating. This effect is referred to as cross-orientation suppression. We have examined the spatial organization and tuning characteristics of this suppressive effect with the use of extracellular recording techniques. 2. For a total of 75 neurons, we have measured the size of each cell's excitatory receptive field by use of rectangular patches of drifting sinusoidal gratings presented at the optimal orientation and spatial frequency. The length and width of these grating patches are varied independently. Receptive-field length and width are determined from the dimensions of the smallest grating patch required to elicit a maximal response. 3. The extent of the area from which cross-orientation suppression originates has been measured in an analogous manner. Each neuron is excited by a patch of drifting grating the same size as the receptive field. The response to this stimulus is modulated by a superimposed patch of grating having an orthogonal orientation. After selecting the spatial frequency that produces maximal suppression, the response of each cell is examined as a function of the length and width of the orthogonal (suppressive) grating patch. Results from 29 cells show that the dimensions of the orthogonal grating patch required to elicit maximal suppression are similar to, or smaller than, the dimensions of the excitatory receptive field. Thus cross-orientation suppression originates from within the receptive field. 4. For some cells the spatial frequency tuning of the suppressive effect is much broader than the spatial frequency tuning for excitation. In these cases it is possible to find a spatial frequency that produces suppression but not excitation. With the use of a suppressive stimulus having this spatial frequency, we examined the strength of suppression as a function of orientation for 11 cells. These tests show that suppression occurs at all orientations, including the preferred orientation for excitation. In some cases, suppression is somewhat stronger at the preferred orientation for excitation than at any other orientation. 5. For 12 cells we varied the relative spatial phase between the optimally oriented and orthogonal gratings. In all cases the magnitude of suppression is largely independent of the relative spatial phase. 6. For three binocular cells we examined whether the suppressive effect of a grating oriented orthogonal to the optimum could be mediated dichoptically.(ABSTRACT TRUNCATED AT 400 WORDS)