Department of Biomedical Sciences and Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
J Neurophysiol. 2012 Oct;108(8):2292-305. doi: 10.1152/jn.00049.2012. Epub 2012 Aug 1.
The nucleus tractus solitarii (nTS) is the primary termination and integration point for visceral afferents in the brain stem. Afferent glutamate release and its efficacy on postsynaptic activity within this nucleus are modulated by additional neuromodulators and transmitters, including serotonin (5-HT) acting through its receptors. The 5-HT(2) receptors in the medulla modulate the cardiorespiratory system and autonomic reflexes, but the distribution of the 5-HT(2C) receptor and the role of these receptors during synaptic transmission in the nTS remain largely unknown. In the present study, we examined the distribution of 5-HT(2C) receptors in the nTS and their role in modulating excitatory postsynaptic currents (EPSCs) in monosynaptic nTS neurons in the horizontal brain stem slice. Real-time RT-PCR and immunohistochemistry identified 5-HT(2C) receptor message and protein in the nTS and suggested postsynaptic localization. In nTS neurons innervated by general visceral afferents, 5-HT(2C) receptor activation increased solitary tract (TS)-EPSC amplitude and input resistance and depolarized membrane potential. Conversely, 5-HT(2C) receptor blockade reduced TS-EPSC and miniature EPSC amplitude, as well as input resistance, and hyperpolarized membrane potential. Synaptic parameters in nTS neurons that receive sensory input from carotid body chemoafferents were also attenuated by 5-HT(2C) receptor blockade. Taken together, these data suggest that 5-HT(2C) receptors in the nTS are located postsynaptically and augment excitatory neurotransmission.
孤束核(nTS)是脑干中内脏传入的主要终止和整合点。传入谷氨酸的释放及其在该核内突触后活动中的效力受到其他神经调质和递质的调节,包括通过其受体作用的血清素(5-HT)。延髓中的 5-HT(2)受体调节心肺系统和自主反射,但 5-HT(2C)受体在 nTS 中的分布及其在突触传递过程中的作用在很大程度上仍然未知。在本研究中,我们检查了 5-HT(2C)受体在 nTS 中的分布及其在调制水平脑切片中单突触 nTS 神经元兴奋性突触后电流(EPSC)中的作用。实时 RT-PCR 和免疫组织化学鉴定了 nTS 中的 5-HT(2C)受体mRNA 和蛋白质,并提示其位于突触后。在被一般内脏传入神经支配的 nTS 神经元中,5-HT(2C)受体的激活增加了孤束(TS)-EPSC 幅度和输入电阻,并使膜电位去极化。相反,5-HT(2C)受体阻断减少了 TS-EPSC 和微小 EPSC 幅度,以及输入电阻,并使膜电位超极化。来自颈动脉体化学感受器的感觉传入的 nTS 神经元的突触参数也被 5-HT(2C)受体阻断所减弱。综上所述,这些数据表明,nTS 中的 5-HT(2C)受体位于突触后,并增强兴奋性神经传递。