Characterizing a Raphe Chemosensory Amplifier

 描述（由申请人提供）：表征中缝化学感受放大器。项目概要：了解大脑检测和响应CO2/pH（中枢化学敏感性）变化的神经元对于理解稳态调节和化学敏感性失败导致的疾病（如睡眠呼吸暂停、先天性中枢性通气不足综合征和婴儿猝死综合征）的性质至关重要。合成神经递质5-羟色胺（5-HT）或氨基丁酸（GABA）的延髓神经元被认为是一级化学感受神经元。然而，未知的是第二阶化学感觉神经元的身份和特征，负责整合，放大和协调第一阶神经元的活动，以调节对化学感觉刺激的稳态反射反应。我们假设，第一阶β 5 HT和GABA化学感觉神经元相互作用，并驱动一个特定的人口的第二阶神经元，一起形成一个本地的β 5 HT化学感觉放大器（RCA）网络。我们的首要假设是，1阶化学感觉神经元的延髓神经元相互作用，并整合与人口的202 nd阶神经元，形成一个本地网络，提供协调输出到呼吸控制中心。为了验证这一假设，我们有两个目标，以证明：具体目标1：固有的敏感性的β 5 HT和GABA神经元的RCA网络的形状。具体目标2：RCAI整合和放大来自一阶5 HT和/或GABA神经元的输入。拟议的研究将确定神经元表型的以前未表征的，但关键的第二阶化学感觉神经元内的神经元。因此，研究将记录中枢化学敏感性所需的基本细胞网络。结果将建议组织的神经元化学感受系统，并通过贡献有关参与这一重要过程的神经元和网络机制的明确信息来促进对中央化学感受的理解。

 DESCRIPTION (provided by applicant): Characterizing a Raphe Chemosensory Amplifier. Project summary: 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 raph neurons synthesizing the neurotransmitter serotonin (5HT) or aminobutyric acid (GABA) are proposed as 1st order chemosensory neurons. Unknown, however, are the identities and characteristics of 2nd order chemosensory neurons, responsible for integrating, amplifying and coordinating the activities of 1st order neurons, to modulate homeostatic reflex responses to chemosensory stimuli. We postulate that 1st order raph 5HT and GABA chemosensory neurons reciprocally interact and drive a specific population of 2nd order neurons which, together, form a local raph chemosensory amplifier (RCA) network. Our overarching hypothesis is that 1st order chemosensory neurons of the medullary raph interact, and integrate with a population of raph 2nd order neurons, to form a local network which provides coordinated output to respiratory control centers. To test this hypothesis we have two aims, to demonstrate; Specific Aim 1: Intrinsic sensitivity of raph 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 determine the neuron phenotypes of previously uncharacterized but critical 2nd order chemosensory neurons within the raph. As such, studies will document a basic cellular network necessary for central chemosensitivity. Results will suggest an organization of the raph chemosensory system and advance the understanding of central chemoreception by contributing definitive information about the neurons and network mechanisms involved in this vital process.