Neural Circuits and Synapses for Early Visual Processing

项目摘要 我的长期目标是在神经回路的水平上理解视觉处理的生物学基础， 突触我正在哺乳动物视网膜中追求这一目标，在那里我们可以有效地研究组织的自然生长。 体外功能;以及我们对组成回路的细胞类型有基本了解：3-4 光感受器（视杆细胞和视锥细胞）、~50个中间神经元（水平、双极和无长突细胞）和~20个输出 神经元（神经节细胞）。理解视网膜回路的一个主要障碍是视网膜神经元的未知功能。 约40种无长突细胞中的大多数。这些（主要是）抑制性中间神经元在以下方面发挥主要作用： 神经节细胞感受野计算，但我们目前只有四个相当详细的了解 类型，专门用于杆视觉（AII，A17），方向选择性（星爆）和神经调节（多巴胺能）。 其余30多种类型的假设功能包括特征选择性（例如，定向调谐）， 感受野周围的产生，ON和OFF通路之间的“交叉”抑制，以及饲料- ON或OFF通路内的正向抑制。然而，在理解方面存在重大障碍 无长突细胞在视网膜回路中的作用：我们缺乏将特定功能分配给个体的能力。 无长突细胞类型，并且在大多数情况下，我们不知道特定细胞类型的突触后靶点及其 在网络功能中的作用。为了推动该领域的发展，我们建议在备选方案之间进行测试 新的无长突细胞电路的假设功能，使用综合的，多学科的方法。要求1 将通过记录细胞中的Ca信号来确定遗传鉴定的无长突细胞类型的感受野特性。 它们的树突，神经递质释放的场所。目的2将确定一个特定的无长突细胞类型的 突触后神经节细胞靶点。目的3将确定无长突蛋白的功能作用 通过测量其可逆失活如何影响神经节细胞感受野， 特性.这三种方法的结合将提供比现有方法更大的进步， 研究无长突细胞，并应广泛适用于整个神经回路功能的研究。 哺乳动物中枢神经系统此外，研究无长突细胞的功能及其在 与其他视网膜神经元的相互连接将有助于开发新的诊断方法的长期目标。 和处理（即，光遗传学、假体）用于眼部疾病。

PROJECT SUMMARY 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, where we can efficiently study the tissue's natural function in vitro; and where we have a basic understanding of the cell types that compose the circuits: 3-4 photoreceptors (rods and cones), ~50 interneurons (horizontal, bipolar and amacrine cells), and ~20 output neurons (ganglion cells). A major obstacle to understanding retinal circuitry is the unknown function of the majority of the ~40 types of amacrine cell. These (primarily) inhibitory interneurons play a major role in ganglion cell receptive field computations, but we presently have a fairly detailed understanding of just four types, specialized for rod vision (AII, A17), direction selectivity (starburst) and neuromodulation (dopaminergic). Hypothesized functions for the remaining 30+ types include feature selectivity (e.g., orientation tuning), generation of receptive field surrounds, 'cross-over' inhibition between the ON and OFF pathways, and feed- forward inhibition within either the ON or OFF pathways. However, there are major barriers to understanding the role of amacrine cells in retinal circuitry: we lack the ability to assign specific functions to individual amacrine cell types, and in most cases we do not know a specific cell type's postsynaptic targets and its associated role in network function. To move the field forward, we propose to test between alternative hypothesized functions for novel amacrine cell circuits using an integrated, multidisciplinary approach. Aim 1 will determine receptive field properties of genetically-identified amacrine cell types by recording Ca signals in their dendrites, the sites of neurotransmitter release. Aim 2 will determine a specific amacrine cell type's postsynaptic ganglion cell targets using optogenetics. Aim 3 will determine the functional role of an amacrine cell type in the circuit by measuring how its reversible inactivation affects ganglion cell receptive field properties. The combination of these three approaches will provide major advances over existing methods for studying amacrine cells and should be broadly applicable to the study of neural circuit function throughout the mammalian central nervous system. Furthermore, studying the function of amacrine cells and their interconnections with other retinal neurons will contribute to the long-term goal of developing new diagnoses and treatments (i.e., optogenetic, prosthetic) for eye disease.