Responsiveness to nicotine of neurons of the caudal nucleus of the solitary tract correlates with the neuronal projection target.

Responsiveness to nicotine of neurons of the caudal nucleus of the solitary tract correlates with the neuronal projection target.
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孤束尾核神经元对尼古丁的反应性与神经元投射目标相关。

DOI:
10.1152/jn.00296.2012
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发表时间:
2012
影响因子:
2.5
通讯作者:
Uteshev,VictorV
Uteshev,VictorV
中科院分区:
医学3区
文献类型:
--
作者:
Feng,Lin;Sametsky,EvgenyA;Gusev,AlexanderG;Uteshev,VictorV

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孤束尾侧核(NTS)是内脏感觉-运动信号整合的关键中枢,支持自主神经系统的稳态。这个核的两个关键投射是臂旁核(PbN)和迷走神经背侧运动核(DMV)。PbN整合并主要向前脑传递内脏感觉信息,支持对内脏事件的行为、情绪和内分泌反应,而DMV包含主要支持胃肠反射的副交感神经节前胆碱能运动神经元。尾侧NTS神经元的亚群表达突触前和体树突烟碱乙酰胆碱受体(nAChRs)。然而,尼古丁反应尾侧NTS神经元的解剖鉴定尚未确定。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确定的尾侧NTS神经元测试的假设,这些细胞对尼古丁的反应与其轴突投射的目标。结果表明,大多数的突触上的PbN投射尾侧NTS神经元的多巴胺能末梢不受尼古丁。此外,这些细胞中只有一小部分表达体树突nAChR。与此相反,大多数DMV投射尾侧NTS神经元表现出强大的突触前和体树突对尼古丁的反应。然而,PbN投射神经元也表现出显着较低的背景频率比DMV投射神经元的突触能微型突触后电流。因此,突触前对尼古丁的无反应性可能是由于PbN投射神经元的多巴胺能神经支配不足所致。然而,尾部NTS含有对尼古丁具有靶特异性反应的功能特异性细胞亚群。这些结果可能支持特定自主神经通路和受损自主稳态的选择性靶向治疗策略的发展。
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.
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