Gap junction permeability modulated by dopamine exerts effects on spatial and temporal correlation of retinal ganglion cells’ firing activities

Synchronized activities among retinal ganglion cells (RGCs) via gap junctions can be increased by exogenous dopamine (DA). During DA application, single neurons’ firing activities become more synchronized with its adjacent neighbors. One intriguing question is how the enhanced spatial synchronization alters the temporal firing structure of single neurons. In the present study, firing activities of bullfrog’s dimming detectors in response to binary pseudo-random checker-board flickering were recorded via a multi-channel recording system. DA was applied in the retina to modulate synchronized activities between RGCs, and the effect of DA on firing activities of single neurons was examined. It was found that, during application of DA, synchronized activities between single neuron and its neighboring neurons was enhanced. At the meantime, the temporal structures of single neuron spike train changed significantly, and the temporal correlation in single neuron’s response decreased. The pharmacological study results indicated that the activation of D1 receptor might have effects on gap junction permeability between RGCs. Our results suggested that the dopaminergic pathway participated in the modulation of spatial and temporal correlation of RGCs’ firing activities, and may exert critical effects on visual information processing in the retina.     

Simple model for encoding natural images by retinal ganglion cells with nonlinear spatial integration

A central goal in sensory neuroscience is to understand the neuronal signal processing involved in the encoding of natural stimuli. A critical step towards this goal is the development of successful computational encoding models. For ganglion cells in the vertebrate retina, the development of satisfactory models for responses to natural visual scenes is an ongoing challenge. Standard models typically apply linear integration of visual stimuli over space, yet many ganglion cells are known to show nonlinear spatial integration, in particular when stimulated with contrast-reversing gratings. We here study the influence of spatial nonlinearities in the encoding of natural images by ganglion cells, using multielectrode-array recordings from isolated salamander and mouse retinas. We assess how responses to natural images depend on first- and second-order statistics of spatial patterns inside the receptive field. This leads us to a simple extension of current standard ganglion cell models. We show that taking not only the weighted average of light intensity inside the receptive field into account but also its variance over space can partly account for nonlinear integration and substantially improve response predictions of responses to novel images. For salamander ganglion cells, we find that response predictions for cell classes with large receptive fields profit most from including spatial contrast information. Finally, we demonstrate how this model framework can be used to assess the spatial scale of nonlinear integration. Our results underscore that nonlinear spatial stimulus integration translates to stimulation with natural images. Furthermore, the introduced model framework provides a simple, yet powerful extension of standard models and may serve as a benchmark for the development of more detailed models of the nonlinear structure of receptive fields.     

Retinal ganglion cells can rapidly change polarity from Off to On

Retinal ganglion cells are commonly classified as On-center or Off-center depending on whether they are excited predominantly by brightening or dimming within the receptive field. Here we report that many ganglion cells in the salamander retina can switch from one response type to the other, depending on stimulus events far from the receptive field. Specifically, a shift of the peripheral image--as produced by a rapid eye movement--causes a brief transition in visual sensitivity from Off-type to On-type for approximately 100 ms. We show that these ganglion cells receive inputs from both On and Off bipolar cells, and the Off inputs are normally dominant. The peripheral shift strongly modulates the strength of these two inputs in opposite directions, facilitating the On pathway and suppressing the Off pathway. Furthermore, we identify certain wide-field amacrine cells that contribute to this modulation. Depolarizing such an amacrine cell affects nearby ganglion cells in the same way as the peripheral image shift, facilitating the On inputs and suppressing the Off inputs. This study illustrates how inhibitory interneurons can rapidly gate the flow of information within a circuit, dramatically altering the behavior of the principal neurons in the course of a computation.     

Closed-loop measurements of iso-response stimuli reveal dynamic nonlinear stimulus integration in the retina

Neurons often integrate information from multiple parallel signaling streams. How a neuron combines these inputs largely determines its computational role in signal processing. Experimental assessment of neuronal signal integration, however, is often confounded by cell-intrinsic nonlinear processes that arise after signal integration has taken place. To overcome this problem and determine how ganglion cells in the salamander retina integrate visual contrast over space, we used automated online analysis of recorded spike trains and closed-loop control of the visual stimuli to identify different stimulus patterns that give the same neuronal response. These iso-response stimuli revealed a threshold-quadratic transformation as a fundamental nonlinearity within the receptive field center. Moreover, for a subset of ganglion cells, the method revealed an additional dynamic nonlinearity that renders these cells particularly sensitive to spatially homogeneous stimuli. This function is shown to arise from a local inhibition-mediated dynamic gain control mechanism.     

The role of neuronal synchronization in selective attention

Attention selectively enhances the influence of neuronal responses conveying information about relevant sensory attributes. Accumulating evidence suggests that this selective neuronal modulation relies on rhythmic synchronization at local and long-range spatial scales: attention selectively synchronizes the rhythmic responses of those neurons that are tuned to the spatial and featural attributes of the attended sensory input. The strength of synchronization is thereby functionally related to perceptual accuracy and behavioural efficiency. Complementing this synchronization at a local level, attention has recently been demonstrated to regulate which locally synchronized neuronal groups phase-synchronize their rhythmic activity across long-range connections. These results point to a general computational role for selective synchronization in dynamically controlling which neurons communicate information about sensory inputs effectively.     

Retinal adaptation to object motion

Due to fixational eye movements, the image on the retina is always in motion, even when one views a stationary scene. When an object moves within the scene, the corresponding patch of retina experiences a different motion trajectory than the surrounding region. Certain retinal ganglion cells respond selectively to this condition, when the motion in the cell's receptive field center is different from that in the surround. Here we show that this response is strongest at the very onset of differential motion, followed by gradual adaptation with a time course of several seconds. Different subregions of a ganglion cell's receptive field can adapt independently. The circuitry responsible for differential motion adaptation lies in the inner retina. Several candidate mechanisms were tested, and the adaptation most likely results from synaptic depression at the synapse from bipolar to ganglion cell. Similar circuit mechanisms may act more generally to emphasize novel features of a visual stimulus.     

Global versus local adaptation in fly motion-sensitive neurons

Flies, like humans, experience a well-known consequence of adaptation to visual motion, the waterfall illusion. Direction-selective neurons in the fly lobula plate permit a detailed analysis of the mechanisms responsible for motion adaptation and their function. Most of these neurons are spatially non-opponent, they sum responses to motion in the preferred direction across their entire receptive field, and adaptation depresses responses by subtraction and by reducing contrast gain. When we adapted a small area of the receptive field to motion in its anti-preferred direction, we discovered that directional gain at unadapted regions was enhanced. This novel phenomenon shows that neuronal responses to the direction of stimulation in one area of the receptive field are dynamically adjusted to the history of stimulation both within and outside that area.     

Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells' activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm.     

The local and non-local components of the local field potential in awake primate visual cortex

The Local Field Potential (LFP) is the analog signal recorded from a microelectrode inserted into cortex, typically in the frequency band of approximately 1 to 200 Hz. Here visual stimuli were flashed on in the receptive fields of primary visual cortical neurons in awake behaving macaques, and both isolated single units (neurons) and the LFP signal were recorded from the same unipolar microelectrode. The fall-off of single unit activity as a visual stimulus was moved from near the center to near the edge of the receptive field paralleled the fall-off of the stimulus-locked (evoked) LFP response. This suggests that the evoked LFP strongly reflects local neuronal activity. However, the evoked LFP could be significant even when the visual stimulus was completely outside the receptive field and the single unit response had fallen to zero, although this phenomenon was variable. Some of the non-local components of the LFP may be related to the slow distributed, or non-retinotopic, LFP signal previously observed in anesthetized animals. The induced (not time-locked to stimulus onset) component of the LFP showed significant increases only for stimuli within the receptive field of the single units. While the LFP primarily reflects local neuronal activity, it can also reflect neuronal activity at more distant sites, although these non-local components are typically more variable, slower, and weaker than the local components.     

Local synchronized activity of neurons of different classes in cat primary visual cortex

The goal of the present study was to investigate the local synchronized neuronal activity in the cat visual cortex and the role of different classes of neurons in neural synchrony. Four classes of neurons were identified on the basis of electrophysiological properties of extracellularly recorded cells: RS, FS, IB, and FRB. It was revealed that neurons with short spikes and FRB type of activity were first engaged in synchronization. The model study revealed that neurons with the short action potential had more stable synchronized activity.     

Retinal ganglion cells are autonomous circadian oscillators synthesizing N-acetylserotonin during the day

Retinal ganglion cells send visual and circadian information to the brain regarding the environmental light-dark cycles. We investigated the capability of retinal ganglion cells of synthesizing melatonin, a highly reliable circadian marker that regulates retinal physiology, as well as the capacity of these cells to function as autonomous circadian oscillators. Chick retinal ganglion cells presented higher levels of melatonin assessed by radioimmunoassay during both the subjective day in constant darkness and the light phase of a light-dark cycle. Similar changes were observed in mRNA levels and activity of arylalkylamine N-acetyltransferase, a key enzyme in melatonin biosynthesis, with the highest levels of both parameters during the subjective day. These daily variations were preceded by the elevation of cyclic-AMP content, the second messenger involved in the regulation of melatonin biosynthesis. Moreover, cultures of immunopurified retinal ganglion cells at embryonic day 8 synchronized by medium exchange synthesized a [3H]melatonin-like indole from [3H]tryptophan. This [3H]indole was rapidly released to the culture medium and exhibited a daily variation, with levels peaking 8 h after synchronization, which declined a few hours later. Cultures of embryonic retinal ganglion cells also showed self-sustained daily rhythms in arylalkylamine N-acetyltransferase mRNA expression during at least three cycles with a period near 24 h. These rhythms were also observed after the application of glutamate. The results demonstrate that chick retinal ganglion cells may function as autonomous circadian oscillators synthesizing a melatonin-like indole during the day.     

Physiological response properties of cat retinal ganglion cells projecting to suprachiasmatic nucleus

The aim of this experiment was to characterize the physiological properties of cat retinal ganglion cells that project to the suprachiasmatic nucleus (SCN). Retrogradely labeled SCN-projecting ganglion cells were recorded extracellularly in vitro. For the first time, this study provides crucial information on visual response properties of ganglion cells in the entrainment circuitry. All recorded cells gave sustained responses (n = 9). Although most of the cells (n = 8) had an "on" center receptive field, one cell showed "on-off" center receptive field properties. The range of receptive field sizes was 2 to 5 deg. For most of the cells tested, the spectral wavelength that evoked peak responses was 500 nm (3 out of 5 cells). All recorded cells (n = 9) preferred still or extremely slow-moving stimuli (3.3 deg/s). These results indicate that cat SCN-projecting cells receive inputs from conventional photoreceptors. The hypothesis that both conventional and cryptochromic photoreceptors are involved in transferring photic signals is discussed.     

Relationship between Size Summation Properties,Contrast Sensitivity and Response Latency in the Dorsomedial and Middle Temporal Areas of the Primate Extrastriate Cortex

Analysis of the physiological properties of single neurons in visual cortex has demonstrated that both the extent of their receptive fields and the latency of their responses depend on stimulus contrast. Here, we explore the question of whether there are also systematic relationships between these response properties across different cells in a neuronal population. Single unit recordings were obtained from the middle temporal (MT) and dorsomedial (DM) extrastriate areas of anaesthetized marmoset monkeys. For each cell, spatial integration properties (length and width summation, as well as the presence of end- and side-inhibition within 15° of the receptive field centre) were determined using gratings of optimal direction of motion and spatial and temporal frequencies, at 60% contrast. Following this, contrast sensitivity was assessed using gratings of near-optimal length and width. In both areas, we found a relationship between spatial integration and contrast sensitivity properties: cells that summated over smaller areas of the visual field, and cells that displayed response inhibition at larger stimulus sizes, tended to show higher contrast sensitivity. In a sample of MT neurons, we found that cells showing longer latency responses also tended to summate over larger expanses of visual space in comparison with neurons that had shorter latencies. In addition, longer-latency neurons also tended to show less obvious surround inhibition. Interestingly, all of these effects were stronger and more consistent with respect to the selectivity for stimulus width and strength of side-inhibition than for length selectivity and end-inhibition. The results are partially consistent with a hierarchical model whereby more extensive receptive fields require convergence of information from larger pools of “feedforward” afferent neurons to reach near-optimal responses. They also suggest that a common gain normalization mechanism within MT and DM is involved, the spatial extent of which is more evident along the cell’s preferred axis of motion.     

Synaptic organization and ionic basis of on and off channels in mudpuppy retina. III. A model of ganglion cell receptive field organization based on chloride-free experiments

A chloride-free environment produces selective changes in the retinal network which include a separation of on and off channels. The identification of chloride-sensitive and insensitivie neuronal activity permits identification of some of the connections and intervening polarities of synaptic interactions which are expressed in ganglion cell receptive field organization. These experiments support previous suggestions that surround antagonism is dependent on horizontal cell activity. In addition they suggest a model of the neuronal connections which subserve on-center, off-center, and on-off ganglion cells. Experimental tests of the on-off ganglion cell model favor the idea that this type of ganglion cell receives inhibitory input from amacrine cells and excitatory activation from depolarizing and hyperpolarizing bipolar cells.     

Coemergence of regularity and complexity during neural network development

With the growing recognition that rhythmic and oscillatory patterns are widespread in the brain and play important roles in all aspects of the function of our nervous system, there has been a resurgence of interest in neuronal synchronized bursting activity. Here, we were interested in understanding the development of synchronized bursts as information-bearing neuronal activity patterns. For that, we have monitored the morphological organization and spontaneous activity of neuronal networks cultured on multielectrode-arrays during their self-executed evolvement from a mixture of dissociated cells into an active network. Complex collective network electrical activity evolved from sporadic firing patterns of the single neurons. On the system (network) level, the activity was marked by bursting events with interneuronal synchronization and nonarbitrary temporal ordering. We quantified these individual-to-collective activity transitions using newly-developed system level quantitative measures of time series regularity and complexity. We found that individual neuronal activity before synchronization was characterized by high regularity and low complexity. During neuronal wiring, there was a transient period of reorganization marked by low regularity, which then leads to coemergence of elevated regularity and functional (nonstochastic) complexity. We further investigated the morphology-activity interplay by modeling artificial neuronal networks with different topological organizations and connectivity schemes. The simulations support our experimental results by showing increased levels of complexity of neuronal activity patterns when neurons are wired up and organized in clusters (similar to mature real networks), as well as network-level activity regulation once collective activity forms.     

A unified neural network model of spatiotemporal processing in X and Y retinal ganglion cells

This article makes use of a push-pull shunting network, which was introduced in the companion article, to model certain properties of X and Y retinal ganglion cells. Input to the push-pull network is preprocessed by a nonlinear mechanism for temporal adaptation, which is ascribed here to photoreceptor dynamics. The complete circuit is used to show that a simple change in receptive field morphology within a single model equation can change the network's response characteristics to closely resemble those of either X or Y cells. Specifically, an increase in width of the receptive field center mechanism is sufficient to account for generation of on-off (Y-like) instead of null (X-like) responses to modulated gratings. In agreement with experimental data, the Y cell on-off response is independent of spatial phase. Also, the model accurately predicts that on-off responses can be observed in X cells for particular stimulus configurations. Taken together, the results show how the retina combines individually inadequate modules to efficiently handle the tasks required for accurate spatial and temporal visual information processing. The model is also able to clarify a number of controversial experimental findings on the nature of spatiotemporal visual processing in the retina.     

Effect of Contrast on Visual Spatial Summation in Different Cell Categories in Cat Primary Visual Cortex

Multiple cell classes have been found in the primary visual cortex, but the relationship between cell types and spatial summation has seldom been studied. Parvalbumin-expressing inhibitory interneurons can be distinguished from pyramidal neurons based on their briefer action potential durations. In this study, we classified V1 cells into fast-spiking units (FSUs) and regular-spiking units (RSUs) and then examined spatial summation at high and low contrast. Our results revealed that the excitatory classical receptive field and the suppressive non-classical receptive field expanded at low contrast for both FSUs and RSUs, but the expansion was more marked for the RSUs than for the FSUs. For most V1 neurons, surround suppression varied as the contrast changed from high to low. However, FSUs exhibited no significant difference in the strength of suppression between high and low contrast, although the overall suppression decreased significantly at low contrast for the RSUs. Our results suggest that the modulation of spatial summation by stimulus contrast differs across populations of neurons in the cat primary visual cortex.     

Reorganization of Receptive Fields of Cortical Field 21a Neurons and Formation of Responses to Moving Visual Stimuli

Using extracellular recording of spike activity from single neurons of field 21a of the cat neocortex, we examined in detail the spatial organization of receptive fields (RFs) of such cells after conditions of presentation of an immobile blinking light spot (a static RF) and moving visual stimuli (dynamic RFs). As was shown, the excitability of different RF subfields of a group of neurons possessing homogeneous on–off organization of the static RF changes significantly depended on the contrast, shape, dimension, orientation, and direction of movement of the applied mobile visual stimulus. This is manifested in changes in the number of discharge centers and shifts of their spatial localization. A hypothesis on the possible role of synchronous activation of the neurons neighboring the cell under study in the formation of an additional neuronal mechanism providing specialization of neuronal responses is proposed.     

A possible explanation of the low-level brightness–contrast illusions in the light of an extended classical receptive field model of retinal ganglion cells

The low-level brightness–contrast illusions constitute a special class within visual illusions. Speculations exist that these illusions may be processed through the filtering action of the retinal ganglion cells without necessitating much intervention from higher order processes of visual perception. Concept of the classical receptive field of the ganglion cell, derived from early physiological studies, prompted the idea that a Difference of Gaussian (DoG) model might explain the low-level illusions. In spite of its many successes, the DoG model fails to explain some of these illusions. It has been shown in this paper that it is possible to simulate those illusions with a model that takes into cognizance the role of the extended classical receptive field     

Coding of natural scenes in primary visual cortex

Natural scene coding in ferret visual cortex was investigated using a new technique for multi-site recording of neuronal activity from the cortical surface. Surface recordings accurately reflected radially aligned layer 2/3 activity. At individual sites, evoked activity to natural scenes was weakly correlated with the local image contrast structure falling within the cells' classical receptive field. However, a population code, derived from activity integrated across cortical sites having retinotopically overlapping receptive fields, correlated strongly with the local image contrast structure. Cell responses demonstrated high lifetime sparseness, population sparseness, and high dispersal values, implying efficient neural coding in terms of information processing. These results indicate that while cells at an individual cortical site do not provide a reliable estimate of the local contrast structure in natural scenes, cell activity integrated across distributed cortical sites is closely related to this structure in the form of a sparse and dispersed code.