Brainstem Gustatory Processing

描述（由申请人提供）：味觉和内脏通路上积累的解剖学、电生理学和药理学数据提出了几个关于孤束核（NST）味觉区功能组织的可验证假设。在之前的资助期间，PI的实验室已经表明，NST中的味觉细胞受到几种神经递质和调节剂的影响，包括兴奋性氨基酸（EAA），γ-氨基丁酸（GABA），P物质（SP）和甲硫氨酸脑啡肽（ENK），来自同侧岛叶皮层（IC）和外侧下丘脑（LH）的离心输入对NST中的味觉神经元产生兴奋或抑制作用和杏仁核中央核（CeA）。该提案寻求资金，以便以显著的方式扩展这些调查结果。第一个具体的目的是调查下行影响的对侧IC和床核的终纹（BNST），另一个来源的下行输入的NST，并确定味觉神经编码的离心调制的影响。这些细胞外的神经生理学实验测试的假设，对侧IC和BNST也调节味觉输入和不同的前脑区域（IC，LH，CeA和BNST）差异改变味觉质量的神经表征。他们还测试的假设，NST神经元投射到臂旁核（PbN）的目标不同的离心输入比本地电路神经元。第二个具体目标解决了EAA，GABA，SP和阿片类药物在NST神经元的兴奋性和抑制性调制中的作用。这些实验测试的假设，兴奋性离心调制是通过EAA或SP介导的，而GABA能或阿片类药物的机制介导的抑制性影响。免疫细胞化学研究解决了这一假设，即PbN投射神经元表达不同的神经递质受体比本地电路神经元。第三个具体目标采用在体内细胞内记录，以确定不同的形态和电生理神经元类型的NST在这些调制电路中的作用。这些实验测试的假设，所有的神经元类型的吻侧NST是味觉和不同的神经元类型表达不同的神经递质受体，并有差异的离心神经元为目标。这些体内实验旨在揭示NST中的突触相互作用以及与该核的连接如何相互作用以控制NST神经元对味觉输入的反应。这些研究将为我们了解中枢味觉系统的功能结构提供新的信息。

DESCRIPTION (provided by applicant): Accumulating anatomical, electrophysiological and pharmacological data on the gustatory and visceral pathways suggest several testable hypotheses about the functional organization of the gustatory zone of the nucleus of the solitary tract (NST). During the previous funding period, the PI's laboratory has shown that taste cells in the NST are influenced by several neurotransmitters and modulators, including excitatory amino acids (EAAs), gamma-aminobutyric acid (GABA), substance P (SP), and met-enkephalin (ENK), and that taste neurons in the NST are excited or inhibited by centrifugal inputs from the ipsilateral insular cortex (IC) and the lateral hypothalamus (LH) and central nucleus of the amygdala (CeA) bilaterally. This proposal seeks funding t o extend these findings in significant ways. T he first Specific Aim is to investigate descending influences of the contralateral IC and the bed nucleus of the stria terminalis (BNST), another source of descending input to the NST, and to determine the effects of centrifugal modulation on gustatory neural coding. These extracellular neurophysiological experiments test hypotheses that the contralateral IC and the BNST also modulate taste input and that different forebrain regions (IC, LH, CeA and BNST) differentially alter the neural representation of taste quality. They also test the hypothesis that NST neurons projecting to the parabrachial nuclei (PbN) are targeted differently by centrifugal inputs than local-circuit neurons. The second Specific Aim addresses the role of EAAs, GABA, SP and opioids in the excitatory and inhibitory modulation of NST neurons. These experiments test hypotheses that excitatory centrifugal modulation is mediated via EAAs or SP, whereas GABAergic or opioid mechanisms mediate inhibitory influences. Immunocytochemical studies address the hypothesis that PbN-projection neurons express different neurotransmitter receptors than local-circuit neurons. The third Specific Aim employs in vivo intracellular recording to determine the role of different morphological and electrophysiological neuron types in the NST in these modulatory circuits. These experiments test hypotheses that all neuron types in the rostral NST are gustatory and that different neuron types express different neurotransmitter receptors and are differentially targeted by centrifugal neurons. These in vivo experiments are designed to reveal how synaptic interactions in the NST and connections to and from this nucleus interact to control the responses of NST neurons to gustatory input. These studies will provide new information to our understanding of the functional organization of the central gustatory system.