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. [unreadable] [unreadable]
NIH ExPorter
NIH ExPorter