Neurotransmission evoked by 5HT-dependent luminal factor

描述（由申请方提供）：既往研究表明，迷走-迷走反射在调节餐后胰酶分泌中起关键作用。在上一个资助期间，我们证明，管腔刺激诱导释放5-HT从粘膜EC细胞，这反过来又激活5-HT 3受体的粘膜迷走神经传入末梢刺激迷走神经初级感觉神经元，以这种方式，5-HT作为旁分泌物质刺激胰腺分泌通过迷走神经胆碱能通路。目前的建议是设计来表征的神经化学传递的迷走神经传入通路的结状神经节神经元的NTS神经元，和迷走神经传出通路的DMN节前神经元的胰腺内神经元，介导胰腺分泌刺激的管腔5-HT依赖性因子。我们推测，谷氨酸和P物质是主要的神经递质负责传入信息从迷走神经初级传入神经元的NTS。DMN的多种神经递质兴奋的活动的整合在调节迷走神经传出信号到胰腺中起着关键作用：NPY和SP刺激，而生长抑素抑制DMN神经元。特定的DMN神经元群可以支配特定的胰腺内神经元，这些神经元含有不同的神经递质。为了验证这一假设，我们计划进行胰腺逆行追踪，c-Fos和神经递质免疫细胞化学表征迷走神经初级传入通路，以及NTS和DMN神经元，这是由管腔刺激激活。通过对结状神经节和孤束核神经元的电生理记录和标记，将进一步证实参与传入神经传入到孤束核的传递的神经递质和受体。我们将记录胰腺迷走神经的放电，并识别DMN刺激激活的胰腺内神经节神经元的化学编码。最后，我们将研究DMN中的各种神经递质的作用，在介导的胰腺分泌刺激管腔5 HT依赖性因子使用清醒的大鼠模型。

DESCRIPTION (provided by applicant): Previous studies demonstrated that vago-vagal reflex plays a crucial role in the mediation of postprandial pancreatic enzyme secretion. During the last funding period, we demonstrated that luminal stimuli induced the release of 5-HT from mucosal EC cells, which in turn activated 5-HT3 receptors on mucosal vagal afferent terminals to stimulate vagal primary sensory neurons; in this manner, 5-HT acts as a paracrine substance to stimulate pancreatic secretion via a vagal cholinergic pathway. The current proposal is designed to characterize the neurochemical transmission in the vagal afferent pathway of nodose ganglia neurons to NTS neurons, and the vagal efferent pathway of DMN preganglionic neurons to intrapancreatic neurons, which mediate pancreatic secretion stimulated by luminal 5-HT-dependent factors. We hypothesize that glutamate and substance P are the major neurotransmitters responsible for transmitting afferent information from vagal primary afferent neurons to the NTS. The integration of activities excited by multiple neurotransmitters at the DMN plays a critical role in modulating the vagal efferent signaling to the pancreas: NPY and SP stimulate, while somatostatin inhibits DMN neurons. Specific groups of DMN neurons may innervate specific intrapancreatic neurons, which contain different neurotransmitters. To test this hypothesis we plan to perform pancreatic retrograde tracing, c-Fos, and neurotransmitters immunocytochemistry to characterize the vagal primary afferent pathway, as well as the NTS and DMN neurons, which are activated by luminal stimulation. Electrophysiological recording followed by labeling of nodose ganglia and NTS neurons will further confirm the neurotransmitters and receptors involved in the transmission of afferent inputs to the NTS. We will record the firing of the vagal pancreatic nerves and identify the chemical codings of the intrapancreatic ganglia neurons activated by DMN stimulation. Finally, we will examine the roles of various neurotransmitters in the DMN in the mediation of pancreatic secretion stimulated by luminal 5HT-dependent factors using a conscious rat model.