Brainstem Esophageal-Gastric Reflexes

描述(申请人提供)：接受性松弛反射(RRR)被认为是协调摄食行为和胃功能的最重要的迷走神经反射机制之一。在对反射的经典描述中，食道扩张，如在进食时发生的，导致迷走神经调节的松弛和运动抑制。这种反射可以在实验中引发，并被认为允许胃等压地接受Instera。然而，最近的报告显示，在进食过程中和进食后，RRR必须在一定程度上暂停，甚至“倒置”，因为在这些时间段，胃转运实际上比禁食期间更快。我们自己的研究表明，在隔夜禁食的大鼠中，食道扩张导致(正如预期的)强大的胃松弛。相反，我们在喂养的大鼠身上的观察显示，食道扩张导致胃张力显著增加。这种由食道扩张引起的与进食相关的胃张力增加在几个小时后逐渐恢复到“纯粹的”胃松弛状态。这种基本迷走神经控制反射功能的戏剧性变化为我们的总体假说提供了基础：迷走神经胃肠控制反射背后的神经回路是高度动态的，并受到与喂养状态相关的因素的调节。我们之前已经证明，外部因素，特别是胃肠激素，直接和戏剧性地调节肠道的迷走神经反射控制。然而，Gl激素重组对内脏传入的反射反应的具体机制还不是很清楚。我们认为胃肠激素的一个子集，特别是CCK和GLP-1，作用于迷走神经背侧复合体中的神经元，以改变孤束核[NTS]中突触前猫胆胺受体的可用性。我们进一步提出，受体种群的这种变化对迷走神经背侧复合体的反射性神经传递模式有显著影响。我们将结合神经胃肠病学、神经生理学和免疫组织化学方法来测试这些建议。这些关于调节迷走神经反射与摄食状态相关的转换机制的研究结果也有助于解释新陈代谢和荷尔蒙参数的变化如何作用于脑干将摄食程序产生电路从“摄食”状态切换到“不摄食”状态。

DESCRIPTION (provided by applicant): The receptive relaxation reflex [RRR] is acknowledged as one of the most important vagal reflex mechanisms coordinating feeding behavior with gastric function. In the classic description of the reflex, distension of the esophagus, as occurs while feeding, causes a vagally-mediated relaxation and suppression of motility. This reflex can be elicited experimentally and is assumed to allow the stomach to accept ingesta isobarically. More recent reports show, however, that the RRR must be some how suspended, or even "inverted" during and after feeding since gastric transit is actually more rapid at these times than during fasting. Our own studies show that in rats fasted overnight, esophageal distention causes (as expected) a powerful gastric relaxation. Conversely, our observations in fed rats show that esophageal distention induces a significant increase in gastric tone. This feeding-related increase in gastric tone induced by esophageal distention gradually reverts back to a "pure" gastric relaxation after few hours. This dramatic change in the function of such an essential vagal control reflex provides the basis for our overarching hypothesis: Neural circuits underlying vago-vagal gastrointestinal control reflexes are highly dynamic and regulated by factors associated with feeding status. We have previously shown that extrinsic factors, especially gastrointestinal hormones, directly and dramatically modulate vago-vagal reflex control of the gut. However, the specific mechanisms by which Gl hormones can reorganize a reflex response to a visceral afferent input are not well understood. We propose that a subset of gut hormones, in particular, CCK and GLP-1, act on neurons in the dorsal vagal complex to alter the availability of presynaptic catcholamine receptors in the solitary nucleus [NTS]. We propose further that this shift in receptor population has a dramatic effect on reflex neurotransmission patterns in the dorsal vagal complex. We will apply a combination of neurogastroenterological, neurophysiological and immunohistochemical methods to test these proposals. Results from these studies on mechanisms regulating the feeding-state-related switching of vago-vagal reflexes could also help explain how changes in metabolic and hormonal parameters can act to switch ingestion program generation circuits in the brainstem from a "feeding" to "not feeding" state.