Neural Circuitry in the Caudal Solitary Complex

描述：大脑对胃肠功能的调节是一种 能量动态平衡的重要但未被充分理解的组成部分 人类。这个项目的长期目标是了解当地的 脑干孤立性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性突触接触 消化道孤束核(NTS)突起神经元 通过高等大脑进一步整合之前的消化系统信息 区域和最终激活胃部的运动输出。包括在 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 背侧运动神经元与迷走运动神经元的反射-环路相互作用 迷走神经核(DMV)。虽然尾侧的神经回路 孤立性复合体是内脏感觉运动的功能底物 与摄食行为、局部突触连接有关的整合 该地区还没有得到充分的描述。我们将使用全细胞膜片钳 脑片上的记录以研究大脑的功能组织 尾部孤立复合体。我们将在神经元的基础上识别神经元 活体标记与近端胃的功能联系 方法：研究方法。我们还将把突触反应与数量 使用生物细胞素标记技术的形态特征。两者都是电气的 笼养动物初级内脏感觉输入的刺激和光激活 谷氨酸刺激切片内的离散部位将用于 研究该区域由氨基酸介导的局部突触回路。这个 该提案的具体目标旨在测试有关 孤立性复合体的突触回路。的具体假设 建议的研究如下：1)孤束核内与胃相关的主神经元是 被局部GABA能神经元的会聚系统抑制(即，外侧 抑制)；2)小的、假定的抑制性NTS神经元被局部激活 兴奋性NTS神经元；3)DMV内的胃投射神经元 被NTS输入直接抑制。这些实验将导致一个 对孤束核内和丘脑下丘脑区之间神经元连接的理解 孤独的情结。这一信息与机械论高度相关 对摄食行为的理解，如接受性放松和 在胃里的食宿。它还将增进对 消化系统相关疾病治疗的作用机制。

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.