Vestibular Regulation of Respiratory Muscle Activity

描述(由申请人提供)：呕吐是隔膜和腹肌共同收缩的一种刻板模式的结果，产生高胃内压。这个应用程序的目标是破译产生呕吐的延髓电路对前庭输入的处理，并确定这一信号处理如何受到其他可能引起呕吐的输入的影响。特定目标1将绘制由刺激前庭感受器引起的呕吐和伴随恶心期间激活的神经元的位置，并将这些位置与由胃肠道(GI)输入触发的呕吐期间的激活位置进行比较。具体目标2将利用前庭核(VN)亚区的失活来识别产生前庭诱发呕吐的关键区域。一旦包含参与产生呕吐的神经元的脑干区域被确定，随后的实验将确定这些区域的细胞对自然前庭刺激加上GI受体激活的反应。具体目标3将考虑孤束核(NTS)和孤束核(VN)的神经元反应，这两个核分别接受来自外周的GI和迷路输入，可引起呕吐和恶心。具体目标4A将确定作为呕吐模式生成器组成部分的一个区域的神经元的反应：位于NTS和面后核之间的背侧延髓外侧被盖区(LTF)。具体目标4B将考虑PBN对信号的处理，PBN参与将内脏感觉信号传递到前脑，以深入了解前庭和内脏输入的整合在这一区域如何不同，该区域对产生恶心和产生呕吐的延髓元素至关重要。在目标4的结论中，我们将彻底采样主要脑干区域中神经元对迷路刺激的反应，这些区域参与触发和协调呕吐和伴随的情感反应。我们还将系统地确定前庭信号如何在从VN传递到NTS，最后传递到LTF和PBN的过程中在呕吐回路中转换。此外，我们将确定其他呕吐信号的存在如何影响迷路输入的处理，以及这种处理是否在呕吐发作之前或之后立即发生深刻改变。因此，这些研究将提供对导致晕动病产生的信号整合的见解。

DESCRIPTION (provided by applicant): Vomiting is a consequence of a stereotyped pattern of co-contractions of the diaphragm and abdominal muscles that generate high intragastric pressures. The goal of this application is to decipher the processing of vestibular inputs by the medullary circuitry that produces vomiting, and to determine how this signal processing is affected by other inputs that can elicit emesis. Specific Aim 1 will map the locations of neurons activated during vomiting and accompanying nausea elicited by stimulation of vestibular receptors and compare the sites to those activated during emesis triggered by gastrointestinal (GI) inputs. Specific Aim 2 will employ inactivation of subregions of the vestibular nuclei (VN) to identify the area that is essential for producing vestibular-elicited vomiting. Once the brainstem regions containing neurons that participate in generating vomiting are established, subsequent experiments will ascertain the responses of cells in these areas to natural vestibular stimulation added to activation of GI receptors. Specific Aim 3 will consider neuronal responses in nucleus tractus solitarius (NTS) and the VN, which respectively receive GI and labyrinthine inputs from the periphery that can induce emesis and nausea. Specific Aim 4A will determine the responses of neurons in a region that is a component of the vomiting pattern generator: the dorsal medullary lateral tegmental field (LTF) positioned between NTS and the retrofacial nucleus. Specific Aim 4B will consider the processing of signals by PBN, which is involved in transmitting viscerosensory signals to the forebrain, to provide insights into how integration of vestibular and visceral inputs together differs in this region critical for generating nausea and medullary elements that produce vomiting. At the conclusion of Aim 4 we will have thoroughly sampled the responses of neurons to labyrinthine stimulation in the major brainstem areas known to participate in triggering and coordinating vomiting and accompanying affective responses. We will also systematically determine how vestibular signals are transformed in the emetic circuit as they are relayed from the VN to NTS and finally to LTF and the PBN. Furthermore, we will ascertain how the presence of other emetic signals affects the processing of labyrinthine inputs, and whether this processing is profoundly altered immediately before or after an episode of vomiting. As such, the studies will provide insights into the signal integration responsible for the generation of motion sickness.