Brainstem Gustatory Processing

描述（由申请人提供）：积累了关于味觉和内脏通路的解剖学、电生理和药理学数据，提出了关于孤立束核（NST）味觉带功能组织的几个可测试的假设。在之前的资助期间，PI的实验室已经证明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（EAAs）， γ -氨基丁酸（GABA）， P物质（SP）和氨基脑啡肽（ENK）， NST中的味觉神经元受到来自同侧岛叶皮质（IC）和外侧下丘脑（LH）的离心输入的兴奋或抑制杏仁核中央核（CeA）。本提案寻求资金，以重大方式扩展这些发现。第一个特定目的是研究对侧IC和尾纹床核（NST的另一个下行输入源）的下行影响，并确定离心调制对味觉神经编码的影响。这些细胞外神经生理实验验证了这样的假设，即对侧中脑皮层和中脑皮层也调节味觉输入，以及不同的前脑区域（中脑皮层、中脑皮层、中脑皮层和中脑皮层）不同地改变味觉质量的神经表征。他们还验证了一个假设，即投射到臂旁核（PbN）的NST神经元受到离心输入的目标不同于局部回路神经元。第二个特定目的是解决EAAs， GABA， SP和阿片样物质在NST神经元兴奋性和抑制性调节中的作用。这些实验验证了兴奋性离心调节是通过EAAs或SP介导的假设，而gaba能或阿片机制介导抑制作用。免疫细胞化学研究提出pbn -投射神经元与局部回路神经元表达不同的神经递质受体的假设。第三个特异性目的采用体内细胞内记录来确定不同形态和电生理神经元类型在NST中在这些调节回路中的作用。这些实验验证了吻侧NST中所有类型的神经元都是味觉的假设，以及不同类型的神经元表达不同的神经递质受体，并被离心神经元不同地靶向。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。这些研究将为我们理解中枢味觉系统的功能组织提供新的信息。

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.