Brainstem Gustatory Processing

描述(由申请人提供)：关于味觉和内脏通路的解剖学、电生理学和药理学数据的积累提出了几个关于孤束核(NST)味觉带功能组织的可测试假说。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)和甲硫氨酸脑啡肽(ENK)，NST中的味觉神经元可受到来自同侧岛叶皮质(IC)、下丘脑外侧(LH)和杏仁中央核(CEA)的离心性传入的兴奋或抑制。这项提案寻求资金，以便以重要的方式扩大这些发现。第一个特殊目的是研究对侧IC和终纹床核(BNST)对NST下行输入的另一来源的下行影响，并确定离心力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以下假设：对侧IC和BNST也调节味觉输入，不同的前脑区域(IC、LH、CEA和BNST)不同地改变味觉质量的神经表征。他们还测试了投射到臂旁核(PBN)的NST神经元在离心力输入下的靶向不同于局部环路神经元的假设。第二个特定目的是研究EaAs、GABA、SP和阿片类物质在NST神经元兴奋性和抑制性调制中的作用。这些实验验证了兴奋性离心调制是通过EaAs或SP介导的假说，而GABA能或阿片类机制则介导了抑制效应。免疫细胞化学研究表明，PBN投射神经元表达不同于局部环路神经元的神经递质受体。第三个特定目的是利用活体细胞内记录来确定NST中不同形态和电生理神经元类型在这些调制电路中的作用。这些实验验证了这样的假设，即NST吻部的所有神经元类型都是味觉的，不同类型的神经元表达不同的神经递质受体，并且是离心神经元的不同靶点。这些活体实验旨在揭示NST内的突触相互作用以及进出该核的联系如何相互作用，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.