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）：生物体使用传入的感官信息以有意义的方式调整其电机输出的过程对于与环境的成功互动至关重要。介导这种感觉运动整合的神经回路的早期开发过程中的正确接线对于生物存活至关重要。在开发神经回路时，电路结构和电路中单个神经元的信号传导特性会经历深刻的变化。但是，即使在这些电路完全成熟之前，生物体也可以开始与环境有意义地相互作用。这表明，基于电路的发育状态，感官处理和行为为基础的神经回路可以采用不同的策略来执行其功能。发生这种情况的过程仍然晦涩难懂。由于人们认为几种人类神经发育障碍是由于早期发育过程中不适当的神经回路形成而导致的，因此了解这些电路发展的基本机制很重要。 我们的建议集中于Xenopus laevis Tadpole的发展视角作为解决这些问题的模型系统。 Tectum及其哺乳动物同源物（上丘）获得了视网膜以及其他感觉方式的直接输入。它功能可以整合视觉和其他感官信息，并将其转换为方向行为。众所周知，t可以迅速远离接近物体，这种回避行为需要通过底部的当地电路进行处理。尚不清楚这些本地电路是如何发展的，也不知道该电路的组织和响应特性如何与视觉引导的运动行为有关。我们建议将行为分析，体内和体外电生理学以及神经元种群的体内CA ++成像结合在一起，以解决tectum如何整合视觉信息并将其转化为视觉避免行为。在第一个目的中，我们表征了刺激的类型，这些刺激触发了视觉回避，并解决了有关这些刺激如何在整体中编码的特定假设。在第二个目的中，我们通过专门针对构造构件与行为相关的刺激的神经元的机制，专门针对构造神经元内在的兴奋性的作用，视网膜直肠突触的特性和局部抑制作用。 这些实验将阐明如何在Tectum中的单个单元格和网络水平上发生的多个发育过程，可以共同起作用，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中枢神经系统补偿发育缺陷的能力提供重要的见解，从而为早期治疗神经发育和视力障碍提供了几种治疗途径。 公共卫生相关性：许多神经和精神病疾病，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有关。相反，人们认为它们是由于不同大脑区域内的微电路水平的异常功能而引起的，并且在开发期间，当这些电路首次形成时，这些异常被认为会在开发过程中产生。因此，了解大脑在发育过程中建立大脑的微电路的基本机制，以及如何以及何时出现这些微电路的功能性能，是理解为什么神经回路在某些神经系统疾病期间异常发展的至关重要的一步，对于开发新的治疗策略很重要。