Cellular basis of visually-guided behavior during development

发育过程中视觉引导行为的细胞基础

• 批准号: 7785246
• 负责人: CARLOS D AIZENMAN
• 金额: $ 37.43万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7785246
• 关键词: Address; Amblyopia; Animal Model; Architecture; Autistic Disorder; Behavior; Behavioral; Behavioral Assay; Biological Models; Brain; Brain region; Cells; Characteristics; Cues; Development; Developmental Process; Early treatment; Electrophysiology (science); Environment; Epilepsy; Equilibrium; Event; Exhibits; Homologous Gene; Human; Image; In Vitro; Individual; Ion Channel; Laboratories; Link; Measures; Mediating; Mental disorders; Mining; Modality; Molecular; Motor; Motor output; Neurodevelopmental Disorder; Neurologic; Neurons; Organism; Output; Pattern; Performance; Physiological; Population; Process; Property; Rana; Recurrence; Retina; Retinal; Role; Schizophrenia; Sensory; Sensory Process; Signal Transduction; Specificity; Staging; Stimulus; Structure; Swimming; Synapses; Tadpoles; Tectum Mesencephali; Testing; Therapeutic; Time; Vision Disorders; Visual; Work; Xenopus laevis; avoidance behavior; base; hindbrain; improved; in vivo; indium arsenide; insight; nervous system disorder; neural circuit; novel; novel therapeutics; public health relevance; relating to nervous system; research study; response; retinotectal; sensory stimulus; superior colliculus Corpora quadrigemina; visual information; visual stimulus

DESCRIPTION (provided by applicant): 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 development of neural circuits mediating this sensorimotor integration is essential for organism survival. In developing 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, receive direct input from the retina as well as from other sensory modalities. It functions to integrate visual and other sensory information, and transform this into orienting behavior. Tadpoles are known to rapidly swim away from approaching 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 analyses, 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 deficits, opening several therapeutic avenues for the early treatment of neurodevelopmental and vision disorders. PUBLIC HEALTH RELEVANCE: Many neurological and psychiatric disorders including autism, schizophrenia, epilepsy and amblyopia are not always clearly associated with a well defined neuropathological profile. Rather, they are believed to result from abnormal functioning at the level of microcircuits within different brain regions, and many of these abnormalities are thought to arise during development when these circuits are first formed. Understanding the basic mechanisms by which the microcircuitry of the brain becomes established during development, and how and when functional properties of these microcircuits emerge, is therefore a crucial step towards understanding why neural circuits develop abnormally during some neurological disorders, and is important for developing novel therapeutic strategies.

描述（由申请人提供）：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是与环境成功互动的基础。介导这种感觉运动整合的神经回路早期发育过程中的正确接线对于生物体的生存至关重要。在神经回路的发展过程中，回路结构和回路内单个神经元的信号传导特性都发生了深刻的变化。然而，即使在这些回路完全成熟之前，生物体就可以开始与其环境进行有意义的相互作用。这表明感觉处理和行为的神经回路可以根据回路的发育状态采用不同的策略来执行其功能。这种情况发生的过程仍然不清楚。由于多种人类神经发育障碍被认为是由早期发育过程中不适当的神经回路形成引起的，因此了解这些回路发育的基本机制非常重要。 我们的提案侧重于非洲爪蟾蝌蚪发育中的视顶盖作为解决这些问题的模型系统。顶盖及其哺乳动物同源物上丘接收来自视网膜以及其他感觉方式的直接输入。它的功能是整合视觉和其他感官信息，并将其转化为定向行为。众所周知，蝌蚪会快速游离接近的物体，这种回避行为需要顶盖内的局部电路进行处理。目前尚不清楚这些局部回路是如何发育的，也不知道该回路的组织和反应特性的发育变化如何与视觉引导的运动行为相关。我们建议结合使用行为分析、体内和体外电生理学以及神经元群体的体内 Ca++ 成像，来解决顶盖如何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，我们描述了触发视觉回避的刺激类型，并提出了有关这些刺激如何在顶盖中编码的具体假设。在第二个目标中，我们通过特别关注顶盖神经元内在兴奋性的作用、视网膜顶盖突触的特性以及局部抑制的作用来解决顶盖神经元编码行为相关刺激的机制。 这些实验将阐明已知在顶盖的单细胞和网络水平上发生的多个发育过程如何协同工作，以优化其将视觉输入转化为运动行为的能力。了解神经回路调整多种特性以实现稳定功能的基本机制，将为了解中枢神经系统补偿发育缺陷的能力提供重要的见解，为神经发育和视力障碍的早期治疗开辟多种治疗途径。 公共卫生相关性：许多神经和精神疾病，包括自闭症、精神分裂症、癫痫和弱视，并不总是与明确的神经病理学特征明确相关。相反，它们被认为是由不同大脑区域内的微电路水平的异常功能引起的，并且其中许多异常被认为是在这些电路首次形成时的发育过程中出现的。因此，了解大脑微电路在发育过程中建立的基本机制，以及这些微电路的功能特性如何以及何时出现，是理解为什么神经电路在某些神经系统疾病期间异常发育的关键一步，并且对于开发新的神经回路非常重要。治疗策略。