Cellular basis of visually-guided behavior during development

项目摘要 生物体利用传入的感官信息来调节其有意义的运动输出的过程。 方式是与环境成功互动的基础。在早期开发过程中正确布线- 调节这种感觉运动整合的神经回路的形成对生物体的生存至关重要。在开发中- ING神经电路电路结构和电路内单个神经元的信号特性 正在经历深刻的变化。然而，生物体可以开始与他们的环境进行有意义的互动 甚至在这些电路完全成熟之前。这表明，神经回路是感觉处理的基础 行为可以根据电路的发育情况，采用不同的策略来实现其功能 州政府。发生这种情况的过程仍然不清楚。因为人类的几种神经发育障碍 被认为是由于早期发育中不适当的神经回路形成所致，重要的是 了解这些电路发展的基本机制。 我们的建议是以非洲爪哇蝌蚪顶盖的发育为模型系统 解决这些问题。顶盖及其哺乳动物同源的上丘接受直接输入 从视网膜和其他感官形式。它的功能是将视觉和其他感官整合在一起- 队形，并将其转化为定向行为。众所周知，蝌蚪会迅速游走，远离接近- 这种回避行为需要由顶盖内的局部电路进行处理。目前尚不清楚 这些局部环路是如何发展的，也不是组织和反应特性的发展变化 该电路与视觉引导的运动行为有关。我们建议使用行为分析的组合- 体内和体外神经元群体的电生理学和体内钙成像，以解决如何 顶盖整合视觉信息，并将其转化为视觉回避行为。在第一个目标中，我们 描述触发视觉回避的刺激类型，并解决有关如何 这些刺激被编码在顶盖。在第二个目标中，我们解决了神经元在 顶盖通过专注于顶盖神经元固有的作用来编码与行为相关的刺激 兴奋性，视网膜顶盖突触的特性，以及局部抑制的作用。 这些实验将阐明已知的多个发育过程是如何在单个细胞上发生的 和顶盖中的网络级别，可以协同工作，优化其将视觉输入转换为运动的能力 行为。了解神经回路调节多种属性的基本机制以实现 稳定的功能将为了解中枢神经系统补偿发育缺陷的能力提供重要的洞察力。 CITS，为神经发育和视力障碍的早期治疗开辟了几条治疗途径。

Project Summary The process by which organisms use incoming sensory information to adjust their motor output in meaningful ways is fundamental to a successful interaction with their environment. Correct wiring during early develop- ment of neural circuits mediating this sensorimotor integration is essential for organismal survival. In develop- ing neural circuits both circuit architecture and the signaling properties of individual neurons within the circuit undergo profound changes. However, organisms can begin to interact meaningfully with their environment even before these circuits are fully mature. This suggests that neural circuits underlying sensory processing and behavior can employ different strategies to carry out their function, based on the circuit's developmental state. The process by which this occurs remains obscure. Since several human neurodevelopmental disorders are believed to result from inappropriate neural circuit formation during early development, it is important to understand the basic mechanisms by which these circuits develop. Our proposal focuses on the developing optic tectum of the Xenopus laevis tadpole as a model system to address these issues. The tectum, and its mammalian homologue the superior colliculus, receives direct input from the retina as well as from other sensory modalities. It functions to integrate visual and other sensory in- formation, and transform this into orienting behavior. Tadpoles are known to rapidly swim away from approach- ing objects, and this avoidance behavior requires processing by local circuits within the tectum. It is not known how these local circuits develop, nor how developmental changes in the organization and response properties of this circuit relate to visually guided motor behavior. We propose to use a combination of behavioral analy- ses, in vivo and in vitro electrophysiology and in vivo Ca++ imaging of neuronal populations, to address how the tectum integrates visual information and transforms it into visual avoidance behavior. In the first aim we characterize the types of stimuli which trigger visual avoidance and address specific hypotheses about how these stimuli are encoded in the tectum. In the second aim, we address the mechanisms by which neurons in the tectum encode behaviorally relevant stimuli, by focusing specifically on the role of tectal neuron intrinsic excitability, the properties of retinotectal synapses, and the role of local inhibition. These experiments will elucidate how multiple developmental processes known to occur at the single cell and network levels in the tectum, can work together to optimize its ability to transform visual input into motor behavior. Understanding the basic mechanisms by which neural circuits adjust multiple properties to achieve stable function will provide important insight into the ability of the CNS to compensate for developmental defi- cits, opening several therapeutic avenues for the early treatment of neurodevelopmental and vision disorders.