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

使用多通道阵列记录评估 Raphé 化学感应放大器网络

• 批准号: 8794665
• 负责人: MICHAEL B. HARRIS
• 金额: $ 15.05万
• 依托单位: UNIVERSITY OF ALASKA FAIRBANKS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8794665
• 关键词: Acidosis; Address; Adopted; Afferent Neurons; Alaska; Alaska Native; Aminobutyric Acids; Amplifiers; Behavioral Research; Bioinformatics; Biomedical Research; Brain; Brain Stem; Carbon Dioxide; Cells; Characteristics; Collaborations; Data; Development; Disease; Failure; Functional disorder; Health; Hypercapnia; In Situ; In Vitro; Individual; Institution; Interneurons; Investigation; Joints; Knowledge; Link; Maintenance; Modeling; Nature; Nervous system structure; Neurobiology; Neurons; Neurosciences; Neurotransmitters; Output; Pathology; Pattern; Physiological; Pilot Projects; Population; Process; Property; Publications; Rattus; Reflex action; Regulation; Research; Research Methodology; Research Support; Resolution; Role; Serotonin; Shapes; Signal Transduction; Sleep Apnea Syndromes; Stimulus; Students; Sudden infant death syndrome; Techniques; Testing; Training; Universities; advanced system; base; cell type; congenital central hypoventilation syndrome; design; extracellular; gamma-Aminobutyric Acid; insight; interest; multi-electrode arrays; network models; operation; raphe nuclei; response

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.

描述（应用程序提供）：关于大脑检测和响应CO2/pH变化（中心化学敏感性）的神经知识对于理解稳态调节和因化学敏感性失败而引起的疾病的性质至关重要，例如睡眠呼吸暂停，诸如Sleemitial Centrial Central Pernitial Pernitial Pernication Pernication Prosistication Proventration Cyndrome和Suttery Iftant Iftant Death Deathdrome综合征。髓质raphe神经元合成神经递质5-羟色胺（5HT）或γ-氨基丁酸（GABA）的髓质神经元被认为是一阶化学感应神经元。然而，未知的是一阶神经元之间的关键潜在互惠相互作用，以及可能整合，扩大和协调一阶神经元的活动的第二阶化学感应神经元的作用，以调节对化学强度刺激的稳态反射反应。我们假设一阶5HT和GABA化学感应神经元之间相互作用，并驱动特定的二阶神经元的特定种群。这些形成了局部Raphe化学体积放大器（RCA）网络。我们的总体假设是，髓质的一阶感觉神经元是通过相互作用和第二阶神经元整合的，以形成局部协调的网络。我们有两个目标。特定目标1：5HT和GABA神经元的固有灵敏度由RCA网络塑造。具体目标2：RCAI从1阶5HT和/或GABA神经元中整合并扩增输入。拟议的研究将确认和本地化，或反驳强奸中关键网络相互作用的存在会影响完整的神经系统内神经元的化学反应性。结果将测试RCA模型的有效性，并建议组织强奸化学感应系统，并通过贡献有关此重要过程所涉及的网络特征的确定信息来提高对中央化学感受的理解。