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

描述（由申请人提供）：了解大脑检测和响应CO2/pH变化的神经元（中枢化学敏感性）对于理解稳态调节和由化学敏感性失败引起的疾病的性质至关重要，例如睡眠呼吸暂停、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（5HT）或γ-氨基丁酸（GABA）的中缝髓神经元被认为是一级化学感觉神经元。然而，未知的是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的作用，这些神经元可能整合、放大和协调一阶神经元的活动，以调节对化学感觉刺激的稳态反射反应。我们假设一级raph<s:1> 5HT和GABA化学感觉神经元之间相互作用，并驱动特定的二级神经元群。它们一起形成了一个局部的拉斐尔化学感觉放大器（RCA）网络。我们的总体假设是，髓系神经系统的一级感觉神经元通过相互作用和二级神经元形成一个局部协调网络。我们有两个目标。具体目标1:raph<s:1> 5HT和GABA神经元的内在敏感性是由RCA网络塑造的。具体目标2:RCAI整合和放大来自一阶5HT和/或GABA神经元的输入。拟议的研究将确认和定位，或驳斥在完整的神经系统中影响神经元化疗反应的关键网络相互作用的存在。结果将测试RCA模型的有效性，并将提出raph<s:1>化学感觉系统的组织，并通过提供有关这一重要过程中涉及的网络特征的明确信息，促进对中枢化学接受的理解。

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.