Mechanism of Homeostatic Plasticity in a Visceral Sensory Circuit

作为对改变传入输入的反应，神经通路可能经历短时间(分钟)和长时间。 周期(天、周)在路径内的调整，以维持生理输出 适当的范围。负责这种动态平衡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，我们检查了 心肺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，这是睡眠呼吸暂停的一种模型。我们正在使用一种组合 电生理、分子和遗传技术，以了解适应(几天/几周) 致孤束核化学感觉突触传递的持续性改变 导致信息传输水平提高的区域，这部分地受到我们建议的 二次动态平衡适应。这些变化被认为是导致动脉压升高的原因之一。 和夸大的化学反射。在前两年中，我们将重点放在 脑出血后三天神经递质的自发释放增加。在第二年 我们阐述了对这种夸大的反应的适应性反应背后的机制，这带来了 突触传递部分恢复正常。我们认为这项研究很重要，不仅是因为它 提供对在特定情况下操纵呼吸和心血管反射的潜在机制的洞察 这也是因为它提供了对神经元传递中可能普遍存在的适应的洞察 申请。

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.