Evaluating a Raphé Chemosensory Amplifier Network with Multi-Channel Array Recording

描述(申请人提供)：了解大脑用来检测和响应二氧化碳/pH(中枢化学敏感性)变化的神经元的知识，对于了解体内平衡调节和因化学敏感性失败而导致的疾病的性质至关重要，如睡眠呼吸暂停、先天性中枢低通气综合征和婴儿猝死综合征。合成神经递质5-羟色胺(5-羟色胺)或氨基丁酸(γ-氨基丁酸)的延髓中缝神经元被认为是一级化学感觉神经元。然而，尚不清楚一阶神经元之间的关键潜在相互作用，以及二阶化学感觉神经元可能整合、放大和协调一阶神经元的活动，以调节对化学感觉刺激的动态平衡反射反应。我们推测，一阶RAPHé5HT和GABA化学感觉神经元之间相互作用，并驱动特定的二阶神经元群体。这些共同构成了本地Raphé化学传感放大器(RCA)网络。我们的主要假设是延髓缝的一阶感觉神经元和二阶感觉神经元通过相互作用整合在一起，形成局部协调网络。我们有两个目标。具体目的1：RCA网络决定拉斐5-羟色胺和GABA神经元的内在敏感性。具体目标2：RCA1整合和放大一阶5-羟色胺和/或GABA神经元的输入。拟议的研究将证实和定位或驳斥在中缝内存在影响神经元在完整神经系统内的化学反应的关键网络相互作用。结果将测试RCA模型的有效性，并将建议拉斐化学感觉系统的组织，并通过提供关于这一重要过程中涉及的网络特征的明确信息来促进对中央化学接收的理解。

DESCRIPTION (provided by applicant): Knowledge of the neurons with which the brain detects and responds to changes in CO2/pH (central chemosensitivity) is critical to understanding both homeostatic regulation and the nature of diseases resulting from failures in chemosensitivity, such as sleep apnea, Congenital Central Hypoventilation Syndrome and the Sudden Infant Death Syndrome. Medullary raphe neurons synthesizing the neurotransmitter serotonin (5HT) or γ-aminobutyric acid (GABA) are proposed as 1st order chemosensory neurons. Unknown, however, are the critical potential reciprocal interactions between 1st order neurons, and the role of 2nd order chemosensory neurons that may integrate, amplify and coordinate activities of 1st order neurons, to modulate homeostatic reflex responses to chemosensory stimuli. We postulate that 1st order raphé 5HT and GABA chemosensory neurons interact between themselves and drive a specific population of 2nd order neurons. Together, these form a local raphé chemosensory amplifier (RCA) network. Our overarching hypothesis is that 1st order sensory neurons of the medullary raphé are integrated by reciprocal interactions and 2nd order neurons to form a local coordinated network. We have two aims. Specific Aim 1: Intrinsic sensitivity of raphé 5HT and GABA neurons is shaped by the RCA network. Specific Aim 2: RCAI integrate and amplify inputs from 1st order 5HT and/or GABA neurons. Proposed studies will confirm and localize, or refute the existence of critical network interactions within the raphé influencing chemo responsiveness of neurons when within an intact nervous system. Results will test the validity of the RCA model, and will suggest an organization of the raphé chemosensory system and advance the understanding of central chemoreception by contributing definitive information about the network characteristics involved in this vital process.