My long-term goal is to relate visual perception to the underlying neuronal circuits and computations. I am starting with the question: how do circuits adjust their properties to the contrast of a visual scene? Contrast adaptation is important for vision: at low contrast, it increases sensitivity to encode small signals; whereas at high contrast, it decreases sensitivity to protect against response saturation. We know this occurs at many levels, from retina through cortex. But to address circuits and cellular mechanisms, I propose to work in mammalian retina, where we know many of the basic cell types and circuits and where visual responses can be recorded intracellularly, in vitro. In retina, contrast adaptation acts over multiple spatial scales. A ganglion cell adapts to temporal contrast over its peripheral receptive field (mm from its dendritic field) but also to contrast over its dendritic field. In either region, contrast reduces the gain of excitatory inputs and causes a shift in the membrane potential, but peripheral contrast causes hyperpolarization, whereas local contrast causes depolarization. Contrast adaptation also acts over multiple temporal scales. For example, changes in synaptic gain persist during high contrast, whereas shifts in the membrane potential slowly decay. We expect that contrast adaptation involves multiple cellular mechanisms, tuned to different spatial and temporal properties of the visual input. We hypothesize that adaptation to contrast in the peripheral receptive field is driven by a network of axon-bearing amacrine cells (inhibitory interneurons) that send signals over mm to ganglion cells, where they open Cl- and K+ channels to hyperpolarize the ganglion cell and inhibit the presynaptic bipolar terminal (Aim 1). The next major question is whether contrast local to the ganglion cell's dendritic field causes adaptation via either a presynaptic mechanism, intrinsic to bipolar cells, or a postsynaptic mechanism in ganglion cells. We will use several approaches to distinguish between these competing hypotheses (Aim 2). We predict that adaptation of spiking responses arises partly through ganglion cell intrinsic properties, including a slowly modulated K+ conductance and an increased spike threshold. We predict that ganglion cell depolarization also drives a feedback circuit by exciting amacrine cells (via gap junctions) that inhibit the ganglion cell (Aim 3). The proposed studies address fundamental mechanisms of ganglion cell physiology that would further our understanding of human vision in health and disease. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014454-03
Application #
7171783
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Mariani, Andrew P
Project Start
2004-12-01
Project End
2009-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
3
Fiscal Year
2007
Total Cost
$290,908
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Park, Silvia J H; Pottackal, Joseph; Ke, Jiang-Bin et al. (2018) Convergence and Divergence of CRH Amacrine Cells in Mouse Retinal Circuitry. J Neurosci 38:3753-3766
Bleckert, Adam; Zhang, Chi; Turner, Maxwell H et al. (2018) GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells. Proc Natl Acad Sci U S A 115:E12083-E12090
Demb, Jonathan B; Clark, Damon A (2017) Vision: These retinas are made for walkin'. Nature 546:476-477
Cui, Yuwei; Wang, Yanbin V; Park, Silvia J H et al. (2016) Divisive suppression explains high-precision firing and contrast adaptation in retinal ganglion cells. Elife 5:
Clark, Damon A; Demb, Jonathan B (2016) Parallel Computations in Insect and Mammalian Visual Motion Processing. Curr Biol 26:R1062-R1072
Byun, Haewon; Kwon, Soohyun; Ahn, Hee-Jeong et al. (2016) Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus. J Comp Neurol 524:2300-21
Demb, Jonathan B; Singer, Joshua H (2015) Functional Circuitry of the Retina. Annu Rev Vis Sci 1:263-289
Park, Silvia J H; Borghuis, Bart G; Rahmani, Pouyan et al. (2015) Function and Circuitry of VIP+ Interneurons in the Mouse Retina. J Neurosci 35:10685-700
Stafford, Benjamin K; Manookin, Michael B; Singer, Joshua H et al. (2014) NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells. J Physiol 592:4877-89
Stafford, Benjamin K; Park, Silvia J H; Wong, Kwoon Y et al. (2014) Developmental changes in NMDA receptor subunit composition at ON and OFF bipolar cell synapses onto direction-selective retinal ganglion cells. J Neurosci 34:1942-8

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