Neurotrophin Regulation of Taste System Development

描述（由申请人提供）：在发育过程中，味觉神经支配是一个严格调控的过程，在这个过程中，特定数量的初级味觉传入投射到口腔的离散区域。脑源性神经营养因子（BDNF）在胚胎发育过程中调节味觉神经支配的数量和位置。我们目前的研究旨在确定这些连接是否和/或如何对中枢味觉发育或味觉功能重要，以及BDNF是否调节出生后味觉系统的发育。拟建的研究结合细胞计数、道示踪、免疫组织化学、电生理和行为测试，在条件和诱导转基因小鼠中：1)确定BDNF是否影响出生后膝部神经节和味芽发育的变化，2)确定胚胎或出生后BDNF是否对中央终末场组织重要，3)确定胚胎或出生后BDNF是否对成年味觉功能重要。总之，这些研究验证了以下假设：1)胚胎BDNF决定了支配味蕾的神经元数量，而味蕾的大小增加以满足出生后的数量。2)中枢神经系统终端场的形成受BDNF和外周连接特异性的调控。3)味觉敏感性降低，但味觉系统在大规模重组后仍能正常工作。这些研究将确定早期周围神经支配模式如何影响味觉系统的持续发育和功能。此外，我们将确定BDNF是否为出生后味觉发育所必需。由于这些实验研究了神经营养因子调节感觉神经支配如何影响持续发育和成人功能，因此该项目对这些强大的信号分子在神经元损伤后重建味觉功能的潜在治疗应用具有重要意义。

DESCRIPTION (provided by applicant): During development, gustatory innervation is a tightly regulated process in which specific numbers of primary taste afferents project to discrete regions of the oral cavity. Brain-derived neurotrophic factor (BDNF) regulates both the number and location of gustatory innervation during embryonic development. Our current research is designed to determine if and/or how these connections are important for central gustatory development or taste function and whether BDNF regulates development of the postnatal taste system. The proposed studies combine cell counting, tract tracing, immunohistochemistry, electrophysiology, and behavioral testing in conditional and inducible transgenic mice to: 1) determine if BDNF influences postnatal changes in geniculate ganglion and taste bud development, 2) determine if embryonic or postnatal BDNF is important for central terminal field organization, and 3) determine if embryonic or postnatal BDNF is important for adult gustatory function. Together, these studies test the hypotheses that: 1) embryonic BDNF determines the number of neurons innervating a taste bud, and taste buds increase in size to meet that number postnatally. 2) CNS terminal field formation is regulated by BDNF and the specificity of peripheral connections. 3) Gustatory sensitivity is reduced but that the taste system still functions despite wide-scale reorganization. These studies will determine how early peripheral innervation patterns influence continued development and function of the taste system. In addition, we will determine whether BDNF is required for postnatal gustatory development. Because these experiments examine how neurotrophin regulation of sensory innervation influences continued development and adult function, this project has important implications for the potential therapeutic use of these powerful signaling molecules in re-establishing gustatory function following neuronal impairment.