Mechanism of Homeostatic Plasticity in a Visceral Sensory Circuit

为了响应不断变化的传入输入，神经通路可能经历短期（分钟）和长期（分钟）。 长期（天，周）的调整，以维持生理输出在一个 合适的范围。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蛋白质分布/功能变化。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 慢性间歇性缺氧（CIH）的反射反应，一种睡眠呼吸暂停模型。我们用的是一种 电生理学、分子和遗传技术，以了解适应情况（数天/数周） 到CI H，引起孤束核化学感觉突触传递的持续变化 导致信息传递水平提高的区域，部分受到我们建议的限制， 次级稳态适应这些变化被认为是导致动脉压升高的原因 和过度的化学反射在两年的第一年，我们专注于潜在的机制， CIH三天后神经递质的自发释放增加。第二年 我们探讨了这种夸张反应的适应性反应的机制， 突触传递部分恢复正常。我们认为这项研究很重要，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的见解，这可能是普遍的， 应用程序.

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.