Synaptic Afferent-Target Relations in Gustatory NTS

描述（由申请人提供）：环境条件对神经元回路的延展性是发育大脑的一个重要特性，有助于促进感知和行为能力的适应性发展。这在感觉系统中特别明显，脑干味觉通路可能是理解竞争性相互作用和活动依赖性重组的合适模型系统，这是神经元可塑性的两种可能机制，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育的重要一步。一项研究计划旨在确定味觉回路是否具有细胞和分子成分，这些成分可能使感觉系统在正常环境刺激的干扰下发生变化。第一项研究旨在获得不同的味觉神经是否集中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、使用三种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。如何以及何时在发展中出现这样的输入收敛将有重要的成果，我们的竞争相互作用的可塑性的作用的理解。第二个和第三个目标的拟议项目将建立在我们现有的知识的味觉脑干的精细突触结构，并表征神经元回路的神经元输入和他们的贡献。具体而言，前和突触后形态的相互作用，特异性不同的谷氨酸受体传入和反馈输入，在味觉传入的NMDA型谷氨酸受体的发育变化将进行研究。这些实验的潜在发现将为两种味觉神经的目标选择性提供新的信息，并强调味觉传入发展作为研究发育可塑性和终身突触稳定性的模型。 公共卫生相关性：早期发育中的感觉和饮食环境极大地影响了发育中的大脑，导致大脑结构和功能的终身变化，以及感觉沟通的缺陷。了解使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育的重要一步。

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.