Cellular basis of visually-guided behavior during development

项目摘要 生物体利用传入的感觉信息以有意义的方式调整其运动输出的过程 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对于生物体的生存是必不可少的。在发展中- 神经回路的电路结构和电路中单个神经元的信号特性 经历了深刻的变化。然而，有机体可以开始与环境进行有意义的互动 甚至在这些电路完全成熟之前。这表明感觉处理的神经回路 根据回路的发育， 状态这种情况发生的过程仍然不清楚。因为几种人类神经发育障碍 被认为是由于在早期发育过程中不适当的神经回路形成，重要的是， 了解这些电路发展的基本机制。 我们的建议集中在非洲爪蟾蝌蚪发育中的视顶盖作为模型系统， 解决这些问题。顶盖和它的哺乳动物同源物上级丘接受直接输入 从视网膜以及从其他感觉形态。它的功能是整合视觉和其他感官- 形成，并将其转化为定向行为。我们知道蝌蚪会迅速游开- 这种回避行为需要顶盖内的局部回路进行处理。目前还不知道 这些局部回路是如何发展的，也不是组织和反应特性的发展变化， 与视觉引导的运动行为有关。我们建议结合行为分析- ses，在体内和体外电生理学和体内钙++成像的神经元群体，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， 描述触发视觉回避的刺激类型，并提出关于如何避免视觉回避的具体假设。 这些刺激被编码在顶盖中。在第二个目标中，我们解决了神经元在 顶盖通过特别关注顶盖神经元内在的作用， 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在单个细胞中发生的多种发育过程 和顶盖中的网络水平，可以共同努力，优化其将视觉输入转化为运动的能力 行为了解神经回路调整多种属性以实现 稳定的功能将为CNS补偿发育缺陷的能力提供重要的见解， 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.