Dissecting Neural Circuit Computations in the Peripheral Visual System

描述(申请人提供)：视觉提供关键的感官输入，指导我们的日常行为；因此，失明可能是我们所经历的最具破坏性的剥夺。在这种情况下，为了将感知与行动联系起来，复杂的视觉场景必须在相对较小的细胞群的神经活动中得到有效的表现；从这些 信号，特别是突出的线索被提取出来，与行为目标相结合，并与适当的反应相联系。这些神经过程可以分解为相对简单的微电路的单独动作，这些微电路是执行基本操作的神经元小组，这些基本操作在大脑中广泛存在，但在不同的背景下具有不同的目的。这项提议将果蝇的视觉系统开发为一个模型，在该模型中，这些微电路的功能可以在分子、细胞和行为水平上进行解剖，并结合遗传学和系统神经科学的技术来获得新的理解。这项建议侧重于视觉处理的核心特征--三个回路相互作用。首先，视觉系统中一个基本的回路相互作用是侧向抑制，这是一种发生在光感受器之间的局部相互作用，已被认为在信息编码中扮演着许多不同的角色。值得注意的是，在任何情况下，我们都不知道这种相互作用在体内的功能。这项提议的第一个目标是定义这些功能，并了解它们在分子和细胞中的实现。其次，许多证据表明，外围视觉系统的元素与特定的线索高度协调，例如，运动模式，具有独特的行为相关性。本项目的第二个目标是定义一个这样的电路的结构和作用机制，并确定该电路的输出如何指导行为。第三，方向选择性在大脑中的出现代表了一种长期存在的、具有丰富理论基础的聚合神经计算。然而，这些理论的电路实现只是不完全理解。这项建议的第三个目标是识别和剖析两个产生不同方向选择调谐特性的微电路。这些研究将广泛地帮助我们了解视网膜在健康和疾病中的功能。由于直接刺激特定电路元件的视网膜假体的发展代表了治疗失明的重要可能性，了解这些电路如何编码与行为相关的视觉信息是一个重要的目标。

DESCRIPTION (provided by applicant): Vision provides critical sensory inputs that guide our routine behaviors; as a result, blindness represents perhaps the most devastating deprivation we can experience. To connect perception to action in this context, complex visual scenes must be efficiently represented in the neural activities of relatively small groups of cells; from these signals, particularly salient cues are extracted, integrated with behavioral goals, and linked to the appropriate responses. These neural processes can be broken down into the individual actions of relatively simple microcircuits, small groups of neurons that perform elementary operations that are widespread in the brain, but which subserve distinct purposes in different contexts. This proposal develops the Drosophila visual system as a model in which the functions of these microcircuits can be dissected at the molecular, cellular and behavioral level, and combines techniques drawn from genetics and systems neuroscience to derive new understanding. This proposal focuses on three circuit interactions that are central features to visual processing. First, one fundamental circuit interaction in the visual system is lateral inhibition, a local interaction that occurs amongst photoreceptors that has been proposed to play a number of distinct roles in information coding. Remarkably, in no context do we know the in vivo functions of this interaction. The first goal of this proposal is to define these functions, ad to understand their molecular and cellular implementation. Second, a number of lines of evidence argue that elements of the peripheral visual system are highly tuned to specific cues, for example, patterns of motion, that are of unique behavioral relevance. The second goal of this project is to define the structure and mechanism of action of one such circuit, and to determine how the output of this circuit guides behavior. Third, the emergence of direction-selectivity in th brain represents a long-standing, paradigmatic neural computation with rich theoretical underpinnings. However, the circuit implementations of these theories are only incompletely understood. The third goal of this proposal is to identify and dissect two microcircuits that produce distinct direction-selective tuning properties. These studies will broadly inform our understanding of retinal function in health and disease. As the development of retinal prostheses that directly stimulate specific circuit elements represents an important treatment possibility for blindness, understanding how these circuits can encode behaviorally-relevant visual information represents an important goal.