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（由申请人提供）：了解大脑用来检测和响应 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（例如睡眠呼吸暂停）的本质至关重要，先天性中枢通气不足综合症和婴儿猝死综合症合成神经递质血清素的中缝神经元。 (5HT) 或 γ-氨基丁酸 (GABA) 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相互作用，以及二阶化学感应神经元可能整合、放大和协调活动的作用。一阶神经元，调节对化学感应刺激的稳态反射反应，我们假设一阶中缝 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群体，这些神经元一起形成了局部中缝化学感觉放大器（RCA）网络，我们的总体假设是中缝髓质的一阶感觉神经元通过相互相互作用和二阶神经元进行整合。我们有两个目标： raphé 5HT 和 GABA 神经元的内在敏感性是由 RCA 网络塑造的。 2：RCAI 整合并放大来自 1 阶 5HT 和/或 GABA 神经元的输入。拟议的研究将确认和定位或反驳在完整的神经系统内影响神经元化学反应性的关键网络相互作用的存在。 RCA 模型的有效性，并将建议 raphé 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来促进对中枢化学感受的理解。