Browsing by Author "Sher, Alexander"
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Item Open Access A polyaxonal amacrine cell population in the primate retina.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014-03) Greschner, Martin; Field, Greg D; Li, Peter H; Schiff, Max L; Gauthier, Jeffrey L; Ahn, Daniel; Sher, Alexander; Litke, Alan M; Chichilnisky, EJAmacrine cells are the most diverse and least understood cell class in the retina. Polyaxonal amacrine cells (PACs) are a unique subset identified by multiple long axonal processes. To explore their functional properties, populations of PACs were identified by their distinctive radially propagating spikes in large-scale high-density multielectrode recordings of isolated macaque retina. One group of PACs exhibited stereotyped functional properties and receptive field mosaic organization similar to that of parasol ganglion cells. These PACs had receptive fields coincident with their dendritic fields, but much larger axonal fields, and slow radial spike propagation. They also exhibited ON-OFF light responses, transient response kinetics, sparse and coordinated firing during image transitions, receptive fields with antagonistic surrounds and fine spatial structure, nonlinear spatial summation, and strong homotypic neighbor electrical coupling. These findings reveal the functional organization and collective visual signaling by a distinctive, high-density amacrine cell population.Item Open Access Anatomical identification of extracellularly recorded cells in large-scale multielectrode recordings.(J Neurosci, 2015-03-18) Li, Peter H; Gauthier, Jeffrey L; Schiff, Max; Sher, Alexander; Ahn, Daniel; Field, Greg D; Greschner, Martin; Callaway, Edward M; Litke, Alan M; Chichilnisky, EJThis study combines for the first time two major approaches to understanding the function and structure of neural circuits: large-scale multielectrode recordings, and confocal imaging of labeled neurons. To achieve this end, we develop a novel approach to the central problem of anatomically identifying recorded cells, based on the electrical image: the spatiotemporal pattern of voltage deflections induced by spikes on a large-scale, high-density multielectrode array. Recordings were performed from identified ganglion cell types in the macaque retina. Anatomical images of cells in the same preparation were obtained using virally transfected fluorescent labeling or by immunolabeling after fixation. The electrical image was then used to locate recorded cell somas, axon initial segments, and axon trajectories, and these signatures were used to identify recorded cells. Comparison of anatomical and physiological measurements permitted visualization and physiological characterization of numerically dominant ganglion cell types with high efficiency in a single preparation.Item Open Access Correlated firing among major ganglion cell types in primate retina.(The Journal of physiology, 2011-01) Greschner, Martin; Shlens, Jonathon; Bakolitsa, Constantina; Field, Greg D; Gauthier, Jeffrey L; Jepson, Lauren H; Sher, Alexander; Litke, Alan M; Chichilnisky, EJRetinal ganglion cells exhibit substantial correlated firing: a tendency to fire nearly synchronously at rates different from those expected by chance. These correlations suggest that network interactions significantly shape the visual signal transmitted from the eye to the brain. This study describes the degree and structure of correlated firing among the major ganglion cell types in primate retina. Correlated firing among ON and OFF parasol, ON and OFF midget, and small bistratified cells, which together constitute roughly 75% of the input to higher visual areas, was studied using large-scale multi-electrode recordings. Correlated firing in the presence of constant, spatially uniform illumination exhibited characteristic strength, time course and polarity within and across cell types. Pairs of nearby cells with the same light response polarity were positively correlated; cells with the opposite polarity were negatively correlated. The strength of correlated firing declined systematically with distance for each cell type, in proportion to the degree of receptive field overlap. The pattern of correlated firing across cell types was similar at photopic and scotopic light levels, although additional slow correlations were present at scotopic light levels. Similar results were also observed in two other retinal ganglion cell types. Most of these observations are consistent with the hypothesis that shared noise from photoreceptors is the dominant cause of correlated firing. Surprisingly, small bistratified cells, which receive ON input from S cones, fired synchronously with ON parasol and midget cells, which receive ON input primarily from L and M cones. Collectively, these results provide an overview of correlated firing across cell types in the primate retina, and constraints on the underlying mechanisms.Item Open Access Efficient coding of spatial information in the primate retina.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012-11) Doi, Eizaburo; Gauthier, Jeffrey L; Field, Greg D; Shlens, Jonathon; Sher, Alexander; Greschner, Martin; Machado, Timothy A; Jepson, Lauren H; Mathieson, Keith; Gunning, Deborah E; Litke, Alan M; Paninski, Liam; Chichilnisky, EJ; Simoncelli, Eero PSensory neurons have been hypothesized to efficiently encode signals from the natural environment subject to resource constraints. The predictions of this efficient coding hypothesis regarding the spatial filtering properties of the visual system have been found consistent with human perception, but they have not been compared directly with neural responses. Here, we analyze the information that retinal ganglion cells transmit to the brain about the spatial information in natural images subject to three resource constraints: the number of retinal ganglion cells, their total response variances, and their total synaptic strengths. We derive a model that optimizes the transmitted information and compare it directly with measurements of complete functional connectivity between cone photoreceptors and the four major types of ganglion cells in the primate retina, obtained at single-cell resolution. We find that the ganglion cell population exhibited 80% efficiency in transmitting spatial information relative to the model. Both the retina and the model exhibited high redundancy (~30%) among ganglion cells of the same cell type. A novel and unique prediction of efficient coding, the relationships between projection patterns of individual cones to all ganglion cells, was consistent with the observed projection patterns in the retina. These results indicate a high level of efficiency with near-optimal redundancy in visual signaling by the retina.Item Open Access Functional connectivity in the retina at the resolution of photoreceptors.(Nature, 2010-10) Field, Greg D; Gauthier, Jeffrey L; Sher, Alexander; Greschner, Martin; Machado, Timothy A; Jepson, Lauren H; Shlens, Jonathon; Gunning, Deborah E; Mathieson, Keith; Dabrowski, Wladyslaw; Paninski, Liam; Litke, Alan M; Chichilnisky, EJTo understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons.Item Open Access High-sensitivity rod photoreceptor input to the blue-yellow color opponent pathway in macaque retina.(Nat Neurosci, 2009-09) Field, Greg D; Greschner, Martin; Gauthier, Jeffrey L; Rangel, Carolina; Shlens, Jonathon; Sher, Alexander; Marshak, David W; Litke, Alan M; Chichilnisky, EJSmall bistratified cells (SBCs) in the primate retina carry a major blue-yellow opponent signal to the brain. We found that SBCs also carry signals from rod photoreceptors, with the same sign as S cone input. SBCs exhibited robust responses under low scotopic conditions. Physiological and anatomical experiments indicated that this rod input arose from the AII amacrine cell-mediated rod pathway. Rod and cone signals were both present in SBCs at mesopic light levels. These findings have three implications. First, more retinal circuits may multiplex rod and cone signals than were previously thought to, efficiently exploiting the limited number of optic nerve fibers. Second, signals from AII amacrine cells may diverge to most or all of the approximately 20 retinal ganglion cell types in the peripheral primate retina. Third, rod input to SBCs may be the substrate for behavioral biases toward perception of blue at mesopic light levels.Item Open Access Identification of a Retinal Circuit for Recurrent Suppression Using Indirect Electrical Imaging.(Current biology : CB, 2016-08) Greschner, Martin; Heitman, Alexander K; Field, Greg D; Li, Peter H; Ahn, Daniel; Sher, Alexander; Litke, Alan M; Chichilnisky, EJUnderstanding the function of modulatory interneuron networks is a major challenge, because such networks typically operate over long spatial scales and involve many neurons of different types. Here, we use an indirect electrical imaging method to reveal the function of a spatially extended, recurrent retinal circuit composed of two cell types. This recurrent circuit produces peripheral response suppression of early visual signals in the primate magnocellular visual pathway. We identify a type of polyaxonal amacrine cell physiologically via its distinctive electrical signature, revealed by electrical coupling with ON parasol retinal ganglion cells recorded using a large-scale multi-electrode array. Coupling causes the amacrine cells to fire spikes that propagate radially over long distances, producing GABA-ergic inhibition of other ON parasol cells recorded near the amacrine cell axonal projections. We propose and test a model for the function of this amacrine cell type, in which the extra-classical receptive field of ON parasol cells is formed by reciprocal inhibition from other ON parasol cells in the periphery, via the electrically coupled amacrine cell network.Item Open Access Mapping nonlinear receptive field structure in primate retina at single cone resolution.(eLife, 2015-10-30) Freeman, Jeremy; Field, Greg D; Li, Peter H; Greschner, Martin; Gunning, Deborah E; Mathieson, Keith; Sher, Alexander; Litke, Alan M; Paninski, Liam; Simoncelli, Eero P; Chichilnisky, EJThe function of a neural circuit is shaped by the computations performed by its interneurons, which in many cases are not easily accessible to experimental investigation. Here, we elucidate the transformation of visual signals flowing from the input to the output of the primate retina, using a combination of large-scale multi-electrode recordings from an identified ganglion cell type, visual stimulation targeted at individual cone photoreceptors, and a hierarchical computational model. The results reveal nonlinear subunits in the circuity of OFF midget ganglion cells, which subserve high-resolution vision. The model explains light responses to a variety of stimuli more accurately than a linear model, including stimuli targeted to cones within and across subunits. The recovered model components are consistent with known anatomical organization of midget bipolar interneurons. These results reveal the spatial structure of linear and nonlinear encoding, at the resolution of single cells and at the scale of complete circuits.Item Open Access Retinal representation of the elementary visual signal.(Neuron, 2014-01) Li, Peter H; Field, Greg D; Greschner, Martin; Ahn, Daniel; Gunning, Deborah E; Mathieson, Keith; Sher, Alexander; Litke, Alan M; Chichilnisky, EJThe propagation of visual signals from individual cone photoreceptors through parallel neural circuits was examined in the primate retina. Targeted stimulation of individual cones was combined with simultaneous recording from multiple retinal ganglion cells of identified types. The visual signal initiated by an individual cone produced strong responses with different kinetics in three of the four numerically dominant ganglion cell types. The magnitude and kinetics of light responses in each ganglion cell varied nonlinearly with stimulus strength but in a manner that was independent of the cone of origin after accounting for the overall input strength of each cone. Based on this property of independence, the receptive field profile of an individual ganglion cell could be well estimated from responses to stimulation of each cone individually. Together, these findings provide a quantitative account of how elementary visual inputs form the ganglion cell receptive field.