Neural circuits and synapses for early visual processing

翻译后摘要：我的长期目标是了解视觉处理的生物学基础的水平， 神经回路和突触。我正在哺乳动物视网膜中实现这一目标， ~70种细胞类型：~3-4种光感受器（取决于物种），~50种中间神经元（水平，双极和 无长突细胞）和~20个输出神经元（神经节细胞）。在过去的一段时间里，我们专注于两个 神经节细胞的类型（ON和OFF α细胞），并阐明了其基本组成部分， 突触输入和对比度适应机制。这些成就使我们能够 将我们的研究扩展到十几种神经节细胞， 功能特性（光诱发突触传导）和结构特性（树突树 内丛状层中的直径和分层水平）。目标1将揭示基本电路 夜视机制，通过确定杆信号是如何传输的，通过一个确定的神经 每种神经节细胞类型。视杆细胞与视杆双极细胞形成突触，而视杆双极细胞反过来又激发AII 无长突细胞; AII细胞直接向某些神经节细胞类型发出信号，并通过 与突触前锥双极末梢形成突触。初步数据显示， OFF神经节细胞类型接受直接的AII细胞突触;另一组接受间接突触， 而第三组缺少与电路的连接并且在昏暗的光线下失去功能。编码视觉 在日光下，每种神经节细胞类型都从一种或多种类型的神经节细胞接收神经元能突触， 但是我们需要测试哪些神经节细胞类型编码谷氨酸释放， NMDA受体（Aim 2）。与其他主要类型的AMPA受体相比，NMDA受体具有 电导是电压依赖性的，缺乏脱敏作用，并且具有相对慢的动力学。我们 我想了解NMDA受体在视觉处理中的作用，作为第一步，我们将 识别哪些神经节细胞类型表达它们。对于每种类型，我们将测试函数表达式 我们将进一步测试这些受体是否有助于高对比度， 正常生理条件下的反应。最后，我们将定量测试NMDA的作用 视觉处理中的受体（Aim 3）。我们将模拟配体门控受体的贡献， 反应，并测试NMDA受体是否优先用于编码低与高 对比度我们将进一步测试NMDA受体介导的反应的缓慢动力学是否 优先编码低时间频率。拟议的研究将产生基本的了解， 视网膜回路和突触如何处理信息，并为理解 损害视杆细胞通路或涉及NMDA受体介导的视网膜疾病 兴奋性毒性

Abstract: My long-term goal is to understand the biological basis of visual processing at the level of neural circuits and synapses. I am pursuing this goal in the mammalian retina, a tissue comprised of ~70 cell types: ~3-4 photoreceptors (depending on species), ~50 interneurons (horizontal, bipolar and amacrine cells) and ~20 output neurons (ganglion cells). Over the past period, we focused on two types of ganglion cell (ON and OFF Alpha cell) and elucidated fundamental components of their synaptic inputs and mechanisms for contrast adaptation. These accomplishments allow us to now expand our studies to a dozen types of ganglion cell that we recognize based on a combination of functional properties (light-evoked synaptic conductance) and structural properties (dendritic tree diameter and stratification level in the inner plexiform layer). Aim 1 will reveal fundamental circuit mechanisms for night vision, by determining how rod signals are transmitted, via an identified neural pathway, to each ganglion cell type. Rods synapse with rod bipolar cells, which in turn excite the AII amacrine cell; the AII cell signals directly certain ganglion cell types and indirectly others by synapsing with the presynaptic cone bipolar terminal. Preliminary data suggest that a small group of OFF ganglion cell types receives direct AII cell synapses; another group receives indirect synapses, whereas a third group lacks connection to the circuit and loses function in dim light. To encode visual signals in daylight, each ganglion cell type receives glutamatergic synapses from one or more types of cone bipolar cell, but we need to test which ganglion cell types encode glutamate release with an NMDA receptor (Aim 2). Compared to the other major type, AMPA receptors, NMDA receptors have a conductance that is voltage-dependent, lacks desensitization and has relatively slow kinetics. We want to understand the role of NMDA receptors in visual processing, and as a first step we will identify which ganglion cell types express them. For each type, we will test for functional expression by applying NMDA directly; we will test further whether these receptors contribute to high contrast responses under normal physiological conditions. Finally, we will test quantitatively the role of NMDA receptors in visual processing (Aim 3). We will model ligand-gated receptor contributions to contrast responses and test whether NMDA receptors are used preferentially for encoding low versus high contrast. We will test further whether the slow kinetics of the NMDA receptor-mediated response encodes preferentially low temporal frequencies. Proposed studies will yield basic understanding of how retinal circuits and synapses process information and provide background for understanding retinal diseases that either compromise the rod pathway or involve NMDA receptor-mediated excitotoxicity.