Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
J Neurophysiol. 2012 Oct;108(7):1884-94. doi: 10.1152/jn.00296.2012. Epub 2012 Jul 18.
The caudal nucleus of the solitary tract (NTS) is the key integrating center of visceral sensory-motor signaling supporting autonomic homeostasis. Two key projections of this nucleus are the parabrachial nucleus (PbN) and the dorsal motor nucleus of the vagus (DMV). The PbN integrates and relays viscerosensory information primarily to the forebrain, supporting behavioral, emotional, and endocrine responses to visceral events, while the DMV contains parasympathetic preganglionic cholinergic motoneurons that support primarily gastrointestinal reflexes. Subsets of caudal NTS neurons express presynaptic and somatodendritic nicotinic acetylcholine receptors (nAChRs). However, the anatomical identification of nicotine-responsive caudal NTS neurons has not been determined. This study used in vivo and ex vivo fluorescent tracing and slice patch-clamp electrophysiological recordings from anatomically identified caudal NTS neurons to test the hypothesis that the responsiveness of these cells to nicotine correlates with the target of their axonal projections. The results demonstrate that the majority of glutamatergic terminals that synapse on PbN-projecting caudal NTS neurons are unaffected by nicotine. Moreover, only a fraction of these cells express somatodendritic nAChRs. In contrast, the majority of DMV-projecting caudal NTS neurons exhibit robust presynaptic and somatodendritic responsiveness to nicotine. However, PbN-projecting neurons also exhibit significantly lower background frequencies of glutamatergic miniature postsynaptic currents than DMV-projecting neurons. Therefore, presynaptic unresponsiveness to nicotine may result from deficient glutamatergic innervation of PbN-projecting neurons. Nevertheless, the caudal NTS contains function-specific subsets of cells with target-specific responsiveness to nicotine. These results may support development of therapeutic strategies for selective targeting of specific autonomic pathways and impaired autonomic homeostasis.
孤束核（NTS）的尾核是支持自主平衡的内脏感觉运动信号的关键整合中心。该核的两个关键投射是臂旁核（PbN）和迷走神经背核（DMV）。PbN 整合和中继内脏感觉信息，主要作用于大脑，支持内脏事件的行为、情绪和内分泌反应，而 DMV 包含副交感节前胆碱能运动神经元，主要支持胃肠道反射。尾核的一些神经元表达突触前和体树突烟碱型乙酰胆碱受体（nAChRs）。然而，对尼古丁反应性尾核神经元的解剖学鉴定尚未确定。本研究使用体内和离体荧光示踪和切片膜片钳电生理记录，从解剖学上鉴定的尾核神经元中，测试了这些细胞对尼古丁的反应性与其轴突投射目标相关的假设。结果表明，与投射到 PbN 的尾核神经元形成突触的谷氨酸能末梢的大多数对尼古丁没有反应。此外，只有一部分细胞表达体树突 nAChRs。相比之下，大多数投射到 DMV 的尾核神经元对尼古丁表现出强烈的突触前和体树突反应性。然而，投射到 PbN 的神经元的谷氨酸能微小突触后电流的背景频率也显著低于投射到 DMV 的神经元。因此，尼古丁对突触前的无反应可能是由于投射到 PbN 的神经元缺乏谷氨酸能神经支配。尽管如此，尾核仍包含具有特定靶标对尼古丁反应性的功能特异性细胞亚群。这些结果可能支持开发针对特定自主途径和受损自主平衡的选择性靶向治疗策略。
