Brainstem Esophageal-Gastic Reflexes

描述（由申请人提供）：接受性松弛反射[RRR]被认为是协调进食行为与胃功能的最重要的迷走神经反射机制之一。在反射的经典描述中，食管的扩张，如进食时发生的，引起迷走神经介导的松弛和运动抑制。这种反射可以在实验中引起，并被认为允许胃接受等压摄入。然而，最近的报告显示，在进食期间和进食后，RRR一定是某种程度的暂停，甚至是“倒置”，因为在这些时候胃的传输实际上比禁食期间更快。我们自己的研究表明，在禁食过夜的大鼠中，食管扩张导致（正如预期的那样）强大的胃松弛。相反，我们在进食大鼠中的观察表明，食管扩张诱导胃张力显著增加。这种由食管扩张引起的与进食相关的胃张力增加在几小时后逐渐恢复到“纯”胃舒张。这种重要的迷走神经控制反射功能的巨大变化为我们的总体假设提供了基础：迷走神经-迷走神经胃肠控制反射的神经回路是高度动态的，并受到与进食状态相关的因素的调节。我们以前已经表明，外在因素，特别是胃肠激素，直接和显着调节迷走神经迷走神经反射控制的肠道。然而，GI激素可以重组对内脏传入输入的反射反应的具体机制还没有很好地理解。我们提出，肠道激素的一个子集，特别是CCK和GLP-1，作用于迷走神经背侧复合体中的神经元，以改变孤核[NTS]中突触前胆碱受体的可用性。我们进一步提出，这种转变的受体人口有一个显着的影响反射神经传递模式的背迷走神经复合体。我们将应用神经胃肠病学，神经生理学和免疫组织化学方法的组合来测试这些建议。从这些研究的结果调节进食状态相关的迷走神经反射的切换机制也可以帮助解释如何在代谢和激素参数的变化可以采取行动，以切换摄取程序生成电路在脑干从“喂养”到“不喂养”的状态。

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.