The spatial structure of a nonlinear receptive field

Department of Physiology and Biophysics, University of Washington, Seattle, Seattle, Washington, USA.
Nature Neuroscience (Impact Factor: 16.1). 09/2012; 15(11):1572-1580. DOI: 10.1038/nn.3225


Understanding a sensory system implies the ability to predict responses to a variety of inputs from a common model. In the retina, this includes predicting how the integration of signals across visual space shapes the outputs of retinal ganglion cells. Existing models of this process generalize poorly to predict responses to new stimuli. This failure arises in part from properties of the ganglion cell response that are not well captured by standard receptive-field mapping techniques: nonlinear spatial integration and fine-scale heterogeneities in spatial sampling. Here we characterize a ganglion cell's spatial receptive field using a mechanistic model based on measurements of the physiological properties and connectivity of only the primary excitatory circuitry of the retina. The resulting simplified circuit model successfully predicts ganglion-cell responses to a variety of spatial patterns and thus provides a direct correspondence between circuit connectivity and retinal output.

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    • "Inhibitory postsynaptic currents (IPSCs) show frequencydoubled (F2) responses characteristic of rectified input (Figure 1K,L). F2 power increases in a steplike fashion between bar widths of 25 μm and 50 μm, suggesting that bipolar cells are likely the cellular substrate for nonlinear subunits (Victor and Shapley, 1979; Demb et al., 2001; Schwartz et al., 2012). Thus, VG3-ACs receive rectified excitatory input from transient ON and OFF bipolar cells, and inhibition from ACs, which themselves appear to be driven by rectified input from possibly the same types of bipolar cells. "
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    ABSTRACT: Retinal circuits detect salient features of the visual world and report them to the brain through spike trains of retinal ganglion cells. The most abundant ganglion cell type in mice, the so-called W3 ganglion cell, selectively responds to movements of small objects. Where and how object motion sensitivity arises in the retina is incompletely understood. In this study, we use 2-photon-guided patch-clamp recordings to characterize responses of vesicular glutamate transporter 3 (VGluT3)-expressing amacrine cells (ACs) to a broad set of visual stimuli. We find that these ACs are object motion sensitive and analyze the synaptic mechanisms underlying this computation. Anatomical circuit reconstructions suggest that VGluT3-expressing ACs form glutamatergic synapses with W3 ganglion cells, and targeted recordings show that the tuning of W3 ganglion cells' excitatory input matches that of VGluT3-expressing ACs' responses. Synaptic excitation of W3 ganglion cells is diminished, and responses to object motion are suppressed in mice lacking VGluT3. Object motion, thus, is first detected by VGluT3-expressing ACs, which provide feature-selective excitatory input to W3 ganglion cells.
    Full-text · Article · May 2015 · eLife Sciences
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    • "Connections with different afferent types may also be stereotypic whereby the postsynaptic cell makes a specific number of connections with each input type. For instance, Type 6 cone bipolar cells provide the majority of the synapses onto the A ON type retinal ganglion cell, whereas Type 7 cone bipolar cells form the minority (Schwartz et al., 2012). Such biased wiring could be attained after a period of increasing connections with all partner types followed subsequently by selective pruning of connections with one type. "
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    ABSTRACT: Across the nervous system, neurons form highly stereotypic patterns of synaptic connections that are designed to serve specific functions. Mature wiring patterns are often attained upon the refinement of early, less precise connectivity. Much work has led to the prevailing view that many developing circuits are sculpted by activity-dependent competition among converging afferents, which results in the elimination of unwanted synapses and the maintenance and strengthening of desired connections. Studies of the vertebrate retina, however, have recently revealed that activity can play a role in shaping developing circuits without engaging competition among converging inputs that differ in their activity levels. Such neurotransmission-mediated processes can produce stereotypic wiring patterns by promoting selective synapse formation rather than elimination. We discuss how the influence of transmission may also be limited by circuit design and further highlight the importance of transmission beyond development in maintaining wiring specificity and synaptic organization of neural circuits.
    Full-text · Article · Sep 2014 · Neuron
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    • "Connections between the type 7 bipolar cells and GC 9, which corresponds to the ON–OFF direction selective ganglion cell, have been examined by presynaptic markers (Lin & Masland, 2005) and the connectome (Helmstaedter et al. 2013). Connections with the A-type ON sustained ganglion cell (GC 12) have been examined by all methods for the type 6 bipolar cell (Schwartz et al. 2012), by synaptic markers and the connectome for the type 7 cone bipolar cells and rod bipolar cells (Morgan et al. 2011). For individual pairs of A-type ON ganglion cells and rod bipolar cells, synaptic markers were present during development but disappeared by postnatal day 21. "
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    ABSTRACT: The visual system has often been thought of as a parallel processor because distinct regions of the brain process different features of visual information. However, increasing evidence for convergence and divergence of circuit connections, even at the level of the retina where visual information is first processed, chips away at a model of dedicated and distinct pathways for parallel information flow. Instead, our current understanding is that parallel channels may emerge, not from exclusive microcircuits for each channel, but from unique combinations of microcircuits. This review depicts the current knowledge and remaining puzzles about the retinal circuit with a focus on the mouse retina. Advances in techniques for labeling cells and genetic manipulations have popularized the use of transgenic mice. We summarize evidence gained from serial electron microscopy, electrophysiology, and light microscopy to illustrate the wiring patterns in mouse retina. We emphasize the need to explore proposed retinal connectivity using multiple methods to verify circuits both structurally and functionally.This article is protected by copyright. All rights reserved
    Preview · Article · Aug 2014 · The Journal of Physiology
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