STRUCTURE FUNCTION RELATIONSHIPS IN BRAINSTEM TASTE CELL

描述：（改编自研究者摘要）已确立 γ-氨基丁酸（GABA）是一种重要的抑制性神经递质 几乎在中枢神经系统的每一个区域，包括吻侧核， 孤束核（rNST）。有趣的是，GABA的作用似乎是 不限于调节成熟神经元的活性。最近的数据 表明GABA在神经发育调节中也很重要， 首先对发育中的脑细胞施加一些营养影响，然后 作为一种兴奋性神经递质， 神经传递素不幸的是，我们对这些因素知之甚少 刺激和调节GABA能神经元的发育变化。那里 然而，有限但有趣的证据表明，一个重要因素是， 适当的激励输入到达。我们建议， 出生后味觉系统的发展提供了一个极好的机会 来研究这个现象。我们的研究基于两个假设：1）GABA 作为兴奋性和抑制性神经递质， 出生后早期rNST味觉神经元的成熟， GABA对味觉敏感性rNST的主要抑制作用的发展 神经元与A型GABA受体数量的增加同时发生， B型GABA受体的重新分布; 2）初始分布和 随后味觉神经元上GABA能突触的重排， 依赖于适当的初级传入输入。我们将检验这些假设 通过以下实验：1）使用光镜和电镜 免疫组织化学来表征A型的表达和处置， 和B型GABA受体在出生后发育的rNST; 2）确定 GABA和GABA受体拮抗剂对神经细胞反应特性的影响 来自出生后早期大鼠的rNST神经元（使用体外和体内记录 技术）; 3）确定GABA能突触在鉴定的细胞上的分布， 在rNST的正常发育过程中的味觉神经元; 4）检查 味觉神经元切断后GABA能突触的分布 鼓索和/或舌咽神经。我们认为 本申请中提出的研究将产生重要和新颖的数据 关于中枢神经系统抑制回路的发展。

DESCRIPTION: (Adapted from the Investigator's Abstract) It is well established that gamma-aminoburyric acid (GABA) is an important inhibitory neurotransmitter in virtually every region of the CNS, including the rostral nucleus of the solitary tract (rNST). Interestingly, it appears that the effects of GABA are not limited to the modulation of the activity of mature neurons. Recent data indicate that GABA is also important in the regulation of neural development, first exerting a number of trophic influences on developing brain cells, then serving as an excitatory neurotransmitter and finally an inhibitory neurotransmitter. Unfortunately, we know very little about the factors that stimulate and regulate the developmental changes in GABAergic neurons. There is, however, limited but intriguing evidence that one important factor is the arrival of APPROPRIATE EXCITATORY INPUT. We propose that the protracted postnatal development of the gustatory system offers an excellent opportunity to study this phenomenon. Our studies are based on two hypotheses: 1) GABA functions as an excitatory as well as an inhibitory neurotransmitter during the early postnatal maturation of gustatory neurons in the rNST, with the development of GABA's predominantly inhibitory effect on taste-sensitive rNST neurons coinciding with an increase in the number of type A GABA receptors and a redistribution of type B GABA receptors; 2) The initial disposition and subsequent rearrangement of GABAergic synapses on gustatory neurons is dependent on appropriate primary afferent inputs. We will test these hypotheses with the following experiments: 1)Use light- and electron-microscopic immunohistochemistry to characterize the expression and disposition of type A and type B GABA receptors during postnatal development of the rNST; 2)Determine the effect of GABA and GABA receptor antagonists on the response properties of rNST neurons from early postnatal rats (using in vitro and in vivo recording techniques); 3)Determine the disposition of GABAergic synapses onto identified gustatory neurons during normal development of the rNST; 4)Examine the distribution of GABAergic synapses onto gustatory neurons following transection of the chorda tympani and/or glossopharyngeal nerves. We believe that the studies proposed in this application will yield significant and novel data regarding the development of inhibitory circuits in the central nervous system.