Functional Circuitry of Visual Adaptation

视觉适应的功能电路

• 批准号: 6873077
• 负责人: Jonathan B Demb
• 金额: $ 30.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873077
• 关键词: amacrine cells; behavioral /social science research tag; calcium flux; electrophysiology; glutamate receptor; guinea pigs; membrane channels; neural transmission; receptor sensitivity; retinal adaptation; retinal bipolar neuron; retinal ganglion; visual pathways; visual perception

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：我的长期目标是将视觉感知与潜在的神经元回路和计算联系起来。我从这个问题开始：电路如何调整它们的属性以适应视觉场景的对比度？对比度适应对视觉很重要：在低对比度下，它增加了对小信号编码的灵敏度;而在高对比度下，它降低了灵敏度，以防止响应饱和。我们知道这发生在许多层面，从视网膜到皮层。但是为了解决电路和细胞机制，我建议在哺乳动物视网膜上工作，我们知道许多基本的细胞类型和电路，并且可以在体外细胞内记录视觉反应。在视网膜中，对比度适应作用于多个空间尺度。神经节细胞适应其外周感受野（距离其树突野mm）的时间对比度，但也适应其树突野的对比度。在这两个区域中，对比度降低兴奋性输入的增益并引起膜电位的偏移，但外周对比度引起超极化，而局部对比度引起去极化。对比度自适应还在多个时间尺度上起作用。例如，突触增益的变化在高对比度期间持续存在，而膜电位的变化缓慢衰减。我们预计，对比度适应涉及多种细胞机制，调整到不同的空间和时间特性的视觉输入。我们假设，在外周感受野的对比度的适应是由轴突轴承无长突细胞（抑制性中间神经元）的网络，发送信号超过毫米的神经节细胞，在那里他们打开Cl-和K+通道hyperplasia的神经节细胞和抑制突触前双极终端（目标1）。下一个主要的问题是对比度局部神经节细胞的树突领域是否会导致适应通过突触前机制，内在的双极细胞，或突触后机制神经节细胞。我们将使用几种方法来区分这些相互竞争的假设（目标2）。我们预测，适应尖峰响应部分通过神经节细胞的内在特性，包括缓慢调制的K+电导和增加的尖峰阈值。我们预测，神经节细胞去极化也通过刺激抑制神经节细胞的无长突细胞（通过间隙连接）来驱动反馈回路（Aim 3）。拟议的研究解决了神经节细胞生理学的基本机制，这将进一步加深我们对健康和疾病中人类视觉的理解。