Functional Circuitry of Visual Adaptation

描述(由申请者提供)：我的长期目标是将视觉感知与潜在的神经元电路和计算联系起来。我从这个问题开始：电路如何根据视觉场景的对比度调整它们的属性？对比度适应对视觉很重要：在低对比度时，它提高了编码小信号的敏感度；而在高对比度时，它降低了敏感度，以防止反应饱和。我们知道这发生在许多层面上，从视网膜到皮质。但为了解决回路和细胞机制，我建议在哺乳动物的视网膜中工作，我们知道许多基本的细胞类型和回路，在那里视觉反应可以在细胞内记录，在体外。在视网膜，对比度适应在多个空间尺度上起作用。神经节细胞不仅适应周围感受野(距离树突野mm)的时间对比度，而且还适应树突野的对比度。在任何一个区域，对比都会降低兴奋性输入的增益，并导致膜电位的移动，但外周对比会导致超极化，而局部对比会导致去极化。对比度适应也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，而膜电位的变化则缓慢衰减。我们预计，对比度适应涉及多种细胞机制，调节到视觉输入的不同空间和时间属性。我们假设，在外周感受野对对比的适应是由轴突承载的无长突细胞(抑制性中间神经元)网络驱动的，该网络通过MM向神经节细胞发送信号，在那里它们打开Cl-和K+通道以超极化神经节细胞并抑制突触前双极终末(目标1)。下一个主要问题是，神经节细胞树突域的局部对比是否通过双极细胞固有的突触前机制或神经节细胞的突触后机制导致适应。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，棘波反应的适应部分是通过神经节细胞的固有特性产生的，包括缓慢调制的K+电导和增大的棘波阈值。我们预测，神经节细胞去极化也通过刺激无长突细胞(通过缝隙连接)来驱动反馈电路，从而抑制神经节细胞(目标3)。拟议的研究涉及神经节细胞生理学的基本机制，这将促进我们对健康和疾病中人类视觉的理解。

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.