Synaptic Afferent-Target Relations in Gustatory NTS

描述(由申请人提供)：神经回路在环境条件下的延展性是大脑发育中的一个重要特性，它促进了知觉和行为能力的适应性发展。这在感觉系统中尤其明显，脑干味觉通路可能是理解竞争相互作用和活动依赖重组的合适模型系统，这两种可能的神经可塑性机制也称为可塑性。了解可塑性的机制是制定策略以避免发育缺陷和促进大脑功能正常发展的重要一步。一项研究计划旨在确定味觉回路是否含有细胞和分子成分，这些成分可能会使感觉系统在正常环境刺激的扰动期间经历变化。第一项研究旨在获得不同的味觉神经是否会聚在单个神经元上的证据。将使用的技术是顺行和逆行追踪解剖学、使用三个不同荧光团的高分辨率共聚焦显微镜和三维电子显微镜的组合。在发展过程中，如何以及何时发生这样的投入汇聚将对我们理解竞争性相互作用在可塑性中的作用产生重要的结果。拟议项目的第二和第三个目标将建立在我们对味觉脑干精细突触结构的现有知识的基础上，并表征谷氨酸能输入及其对神经元回路的贡献。具体地说，将研究突触前和突触后的形态相互作用，不同谷氨酸受体对传入和反馈输入的特异性，以及味觉传入的NMDA型谷氨酸受体的发育变化。这些实验的潜在发现将为两种味觉神经的靶点选择性提供新的信息，并强调味觉传入发育作为研究发育可塑性和终生突触稳定性的模型。 公共卫生相关性：发育早期的感觉和饮食环境极大地影响大脑的发育，导致大脑结构和功能的终生变化，并导致感觉交流的缺陷。了解导致发育途径易受环境影响的机制是制定策略以避免发育缺陷和促进大脑功能正常发展的重要一步。

DESCRIPTION (provided by applicant): The malleability of neuronal circuits by environmental conditions is a crucial property in developing brain in fostering adaptive development of perceptual and behavioral faculties. This is particularly obvious in sensory systems, and brainstem taste pathway is potentially a suitable model system to understand competitive interactions and activity dependent reorganization, two possible mechanisms of neuronal malleability, also termed plasticity. Understanding the mechanisms of plasticity is a major step in developing strategies to avoid developmental defects, and to foster normal development of the brain function. A research program is designed to determine whether taste circuits have cellular and molecular components that may allow sensory systems to undergo changes during perturbation of the normal environmental stimuli. The first study aims to obtain evidence for whether distinct gustatory nerves converge upon individual neurons. The technique that will be utilized is a combination of anterograde and retrograde tract- tracing anatomy, high-resolution confocal microscopy using three different fluorophores and 3-dimentional electron microscopy. How and when in development such input convergences occur will have important outcomes for our understanding of the role of competitive interactions in plasticity. The second and the third aims of the proposed project will build upon our existing knowledge of fine synaptic structure of gustatory brainstem, and characterize glutamatergic inputs and their contribution to neuronal circuits. Specifically, pre- and post-synaptic morphological interactions, specificity of different glutamate receptors to afferent and feedback inputs, and developmental changes in NMDA type glutamate receptors at gustatory afferents will be studied. The potential findings of the proposed experiments shall provide novel information on target selectivity of two gustatory nerves, as well as underlining gustatory afferent development as a model to study developmental plasticity and lifelong synaptic stability. PUBLIC HEALTH RELEVANCE: Sensory and dietary circumstances in early development greatly influence developing brain, leading to lifelong changes in brain structure and function, and to deficits of sensory communication. Understanding the mechanisms that render developing pathways vulnerable to environment is a major step in developing strategies to avoid developmental defects, and to foster normal development of the brain function.