Mechanism of Homeostatic Plasticity in a Visceral Sensory Circuit

内脏感觉回路的稳态可塑性机制

基本信息

批准号：
7895657
负责人：
DIANA L KUNZE
金额：
$ 40.86万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7895657
关键词：
AMPA Receptors ATP phosphohydrolase Accounting Address Afferent Neurons Animals Back Brain Calcium Calcium Channel Cardiovascular system Cell membrane Chronic Development Electric Stimulation Endoplasmic Reticulum Evaluation Fiber Frequencies Gene Expression Genetic Techniques Glutamate Receptor Goals Homeostasis Hypoxia Lead Membrane Membrane Potentials Modeling Molecular Genetics Monitor Neural Pathways Neuraxis Neurons Nucleus solitarius Output Pathway interactions Pattern Physiological Preparation Presynaptic Terminals Process Proteins Reflex action Regulation Rest Role Ryanodine Receptor Calcium Release Channel Ryanodine Receptors Sensory Site Sleep Apnea Syndromes Slice Stimulus Synapses Synaptic Potentials Synaptic Transmission Testing Time Visceral base falls insight laser capture microdissection neurotransmission neurotransmitter release postsynaptic pressure protein distribution receptor relating to nervous system respiratory respiratory reflex response single cell analysis transmission process voltage

项目摘要

In response to changing afferent input, neural pathways may undergo both short term (minutes) and long term (days, weeks) adjustments within the pathway in order to maintain physiological output within an appropriate range. The underlying cellular mechanisms responsible for this homeostatic adaptation may include changes in gene expression and subsequent protein distribution/function. In this study we examine the mechanisms that underlie the long term changes in the central neural component of a cardio-respiratory reflex response to chronic intermittent hypoxia (CIH), a model of sleep apnea. We are using a combination of electrophysiological, molecular and genetic techniques to understand the adaptations (over days/weeks) to CI H that produce sustained changes in chemosensory synaptic transmission in the nucleus of the solitary tract leading to an elevated level of information transfer that is partially restrained by what we propose is a secondary homeostatic adaptation. These changes are thought to contribute to elevated arterial pressure and exaggerated chemoreflexes in CIH. In the first of two years we focus on the mechanisms underlying an increase in spontaneous release of neurotransmitter that occurs after three days of CIH. In the second year we address mechanisms underlying the adaptive response to this exaggerated response and that brings synaptic transmission partially back towards normal. We believe this study is important not only because it provides insight to potential mechanisms for manipulating respiratory and cardiovascular reflexes at specific sites but also because it provides insight to adaptations in neuronal transmission that may be universal in application.

为了响应不断变化的传入输入，神经通路可能会经历短期（分钟）和长期途径内的术语（天、周）调整，以维持生理输出适当的范围。负责这种稳态适应的潜在细胞机制可能包括基因表达和随后的蛋白质分布/功能的变化。在这项研究中，我们检查心肺功能中枢神经成分长期变化的机制对慢性间歇性缺氧（CIH）的反射反应，这是一种睡眠呼吸暂停模型。我们正在使用组合电生理学、分子和遗传技术来了解适应性（数天/数周） CI H 会在孤立神经元核中的化学感应突触传递中产生持续的变化导致信息传输水平提高的通道，这在一定程度上受到我们提出的限制次级稳态适应。这些变化被认为会导致动脉压升高 CIH 中的化学反射过度。在两年的头两年，我们重点研究潜在的机制 CIH 三天后神经递质自发释放增加。第二年我们解决了对这种夸张反应的适应性反应的潜在机制，这带来了突触传递部分恢复正常。我们相信这项研究很重要，不仅因为它提供了对在特定条件下操纵呼吸和心血管反射的潜在机制的见解还因为它提供了对神经元传递适应性的洞察，这可能是普遍存在的应用。