权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of the Gustatory Solitary Nucleus

味觉孤核的发育

基本信息

批准号：
8423351
负责人：
Robert M Bradley
金额：
$ 29.64万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8423351
关键词：
Acute Address Adult Alcohol consumption Animals Anterior Antibodies Axon Behavior Biological Birth Brain Stem Bromodeoxyuridine Cell Cycle Cell Nucleus Cells Cellular Structures Characteristics Data Development Diet Dorsal Electroporation Embryo Embryonic Development Erinaceidae Esthesia Facial nerve structure Feeding behaviors Foundations Fourth ventricle structure Glossopharyngeal nerve structure Goals Immunofluorescence Immunologic Immunohistochemistry In Vitro Intake Investigation Knowledge Lateral Length Life Location Maps Measures Medial Molecular Morphology Nerve Neuraxis Neuroglia Neurons Neurophysiology - biologic function Nucleus solitarius Nutrient Oligodendroglia Pathway interactions Pattern Pattern Formation Peripheral Pharmaceutical Preparations Preparation Process Proliferating Property Quality of life Rattus Regulation Research Rodent Role Sensory Signaling Molecule Slice Staging Synapses System Taste Buds Taste Perception Testing Time Tongue Tube Undifferentiated Vertebrates Western Blotting Whole-Cell Recordings Work feeding knock-down mature animal migration nerve stem cell nerve supply nervous system development neural circuit neural patterning neurodevelopment neuron development neurophysiology postnatal public health relevance receptor reconstruction research study smoothened signaling pathway synaptogenesis tongue papilla

项目摘要

DESCRIPTION (provided by applicant): The rostral portion of the nucleus of the solitary tract (rNST) in the brainstem is the first central taste relay. The rNST receives primary afferent projections from facial and glossopharyngeal nerves, which innervate lingual taste buds and papillae and terminate centrally in a topography that reflects peripheral organization. The time course for and molecular factors involved in proliferation and differentiation of rNST cells are not well understood. Given the importance of an organized taste system for proper function, the long-term objective is to determine how the rNST is established in embryonic rat. The proposed research aims are to determine: the development of solitary tract (ST) projections; the developmental time course of proliferation and differentiation of cell components comprising the rNST; the development of biophysical properties and synapses of rNST neurons; specific molecular factors present in relation to rNST development; and, to manipulate the expression of these factors to determine effects on rNST development. Immunofluorescence will be used to identify the time course for development of neurons and glia that compose the rNST in staged embryos. An in vitro brainstem slice preparation will be used to determine development of neuron function. Immunohistochemical and Western blot approaches will be used to identify the expression of Sonic hedgehog (Shh) signaling factors potentially important for proliferation and differentiation in the NST, and cell cycle regulators across developmental stages. Finally, an explant culture system will be used to isolate the brainstem and manipulate in vitro Shh signaling molecules localized to the rNST and surround. The working hypotheses are that during embryonic development, neural precursors migrate from the fourth ventricle and differentiate to form the earliest rNST, where neurons differentiate before glia; that rNST neurons are functional, but with changing properties, in the embryo; and, that Shh signaling regulates the timing of proliferation and differentiation of rNST neural precursors and emerging neurophysiological function in rNST. Results of these experiments will provide an understanding of the early establishment, organization and function of the rNST and will demonstrate possible molecular pathways involved in that development. This will provide an important foundation for understanding the formation of the primary afferent relay of the gustatory system and lay the groundwork for understanding the demonstrated plasticity that occurs in this relay when environmental manipulations take place during embryogenesis. Furthermore, the proposal addresses essential questions in the process of neural patterning in the CNS.

描述(申请人提供)：脑干中孤束核(RNST)的吻侧部分是第一个中央味觉传递。RNST从面神经和舌咽神经接受初级传入投射，这些神经支配舌味蕾和舌乳头，并在反映周围组织的地形图中央终止。RNST细胞增殖和分化的时间进程和分子因素尚不清楚。鉴于有组织的味觉系统对正常功能的重要性，长期目标是确定RNST是如何在胚胎大鼠中建立的。拟议的研究目的是确定：孤束投射的发展；组成RNST的细胞成分的增殖和分化的发育时间进程；RNST神经元的生物物理特性和突触的发展；与RNST发育有关的特定分子因素；以及，操纵这些因素的表达，以确定对RNST发育的影响。免疫荧光将被用来确定组成RNST的神经元和神经胶质细胞在分期胚胎中的发育过程。一种体外脑干切片制备将用于确定神经元功能的发展。免疫组织化学和Western印迹方法将被用来确定对NST的增殖和分化具有潜在重要性的Sonic hedgehog(Shh)信号因子的表达，以及不同发育阶段的细胞周期调节因子。最后，将使用外植体培养系统分离脑干，并在体外操纵定位于RNST及其周围的Shh信号分子。工作假设是，在胚胎发育过程中，神经前体从第四脑室迁移并分化形成最早的RNST，其中神经元在胶质细胞之前分化；RNST神经元在胚胎中具有功能，但具有变化的性质；Shh信号调控RNST神经前体的增殖和分化以及RNST中新出现的神经生理功能。这些实验的结果将提供对RNST早期建立、组织和功能的理解，并将展示参与这一发展的可能的分子途径。这将为理解味觉系统初级传入中继器的形成提供重要的基础，并为理解胚胎发生过程中环境操纵时在该中继器中发生的可塑性奠定基础。此外，该提案还解决了中枢神经系统神经模式形成过程中的基本问题。