Neural Circuitry in the Caudal Solitary Complex

描述：大脑对胃肠道功能的调节是一种 能量稳态重要但尚未充分理解的组成部分， 人类该项目的长期目标是了解当地 脑干孤束复合体中的神经元连接。作为第一个 迷走神经感觉传入纤维的中枢突触接触 消化道、孤束核（NTS）突起神经元 消化系统的信息，然后通过更高的大脑进一步整合 并最终激活胃的运动输出。纳入 控制自主神经功能的神经元回路是局部突触回路， NTS，来自孤立复合体外的CNS区域的输入，以及 背侧运动中反射回路与迷走运动神经元的相互作用 迷走神经核（DMV）尽管尾部的神经元回路 孤束复合体是内脏感觉运动的功能基质 与进食行为、局部突触连接有关的整合， 该地区没有得到充分的描述。我们将使用全细胞膜片钳技术 记录在大脑切片中，以研究大脑皮层的功能组织。 尾侧孤生复合体我们将根据神经元的 使用体内标记与近端胃的功能性连接 方法.我们还将突触反应与定量 形态学特征，使用生物胞素标记技术。两个电 初级内脏感觉输入刺激和笼状体的光活化 谷氨酸刺激切片内的离散位点， 研究该区域的局部氨基酸介导的突触回路。的 该提案的具体目的是为了测试有关 孤波复合体的突触回路。具体假设如下： 拟进行的研究有：1）NTS中与胃相关的主要神经元， 被局部GABA能神经元的会聚系统抑制（即，横向 抑制）; 2）小的，推定的抑制性NTS神经元被局部激活 兴奋性NTS神经元; 3）DMV中的胃投射神经元 直接由NTS输入抑制。这些实验将导致 了解NTS内和NTS区域之间的神经元连接 孤独的情结这一信息与机械学高度相关， 理解进食行为，如接受性放松， 胃的调节。它还将加强对 治疗消化系统相关疾病的作用机制。

DESCRIPTION: Regulation of gastrointestinal function by the brain is an important but inadequately understood component of energy homeostasis in humans. The long-term objective of this project is to understand the local neuronal connectivity in the brainstem solitary complex. As the site of first central synaptic contact for sensory afferent fibers of the vagus nerve from the digestive tract, neurons in the nucleus tractus solitarius (NTS) process digestive system information prior to further integration via higher brain areas and eventual activation of motor output to the stomach. Included in the neuronal circuits controlling autonomic function are local synaptic circuits in the NTS, inputs from CNS regions outside the solitary complex, and reflex-circuit interactions with vagal motor neurons in the dorsal motor nucleus of the vagus nerve (DMV). Although the neuronal circuitry of the caudal solitary complex is the functional substrate for visceral sensory-motor integration relating to feeding behavior, local synaptic connectivity in the area has not been adequately described. We will use whole-cell patch-clamp recordings in brain slices to investigate the functional organization of the caudal solitary complex. We will identify neurons on the basis of their functional connections with the proximal stomach using in vivo labeling methods. We will also correlate synaptic responses with quantitative morphological features using biocytin labeling techniques. Both electrical stimulation of primary viscerosensory input and photoactivation of caged glutamate to stimulate discrete sites within the slice will be used to investigate the local amino acid-mediated synaptic circuitry of the region. The specific aims of the proposal are designed to test hypotheses regarding the synaptic circuitry of the solitary complex. The specific hypotheses for the proposed research are: 1) Gastric-related principal neurons in the NTS are inhibited by a convergent system of local GABAergic neurons (i.e., lateral inhibition); 2) small, putative inhibitory NTS neurons are activated by local excitatory NTS neurons; and 3) stomach-projecting neurons in the DMV are directly inhibited by NTS input. These experiments will result in an understanding of neuronal connectivity within the NTS and between regions of the solitary complex. This information is highly relevant to the mechanistic understanding of feeding behaviors such as receptive relaxation and accommodation in the stomach. It will also enhance understanding of the mechanisms of action for treatments of digestive system-related disorders.