Y. Oka: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Physiol. 2013 Nov 15;591(22):5509-23. doi: 10.1113/jphysiol.2013.258343. Epub 2013 Aug 19.
Peptidergic neurones play a pivotal role in the neuromodulation of widespread areas in the nervous system. Generally, it has been accepted that the peptide release from these neurones is regulated by their firing activities. The terminal nerve (TN)-gonadotrophin releasing hormone (GnRH) neurones, which are one of the well-studied peptidergic neurones in vertebrate brains, are characterised by their spontaneous regular pacemaker activities, and GnRH has been suggested to modulate the sensory responsiveness of animals. Although many peptidergic neurones are known to exhibit burst firing activities when they release the peptides, TN-GnRH neurones show spontaneous burst firing activities only infrequently. Thus, it remains to be elucidated whether the TN-GnRH neurones show burst activities and, if so, how the mode switching between the regular pacemaking and bursting modes is regulated in these neurones. In this study, we found that only a single pulse electrical stimulation of the neuropil surrounding the TN-GnRH neurones reproducibly induces transient burst activities in TN-GnRH neurones. Our combined physiological and morphological data suggest that this phenomenon occurs following slow inhibitory postsynaptic potentials mediated by cholinergic terminals surrounding the TN-GnRH neurones. We also found that the activation of muscarinic acetylcholine receptors induces persistent opening of potassium channels, resulting in a long-lasting hyperpolarisation. This long hyperpolarisation induces sustained rebound depolarisation that has been suggested to be generated by a combination of persistent voltage-gated Na(+) channels and low-voltage-activated Ca(2+) channels. These new findings suggest a novel type of cholinergic regulation of burst activities in peptidergic neurones, which should contribute to the release of neuropeptides.
肽能神经元在神经系统广泛区域的神经调制中发挥着关键作用。一般来说，人们已经接受了这些神经元的肽释放受其放电活动调节的观点。端神经（TN）-促性腺激素释放激素（GnRH）神经元是脊椎动物大脑中研究得很好的肽能神经元之一，其特征是自发的规则起搏活动，并且 GnRH 被认为调节动物的感觉反应性。尽管许多肽能神经元在释放肽时表现出爆发性放电活动，但 TN-GnRH 神经元仅偶尔表现出自发的爆发性放电活动。因此，仍需要阐明 TN-GnRH 神经元是否表现出爆发活动，如果是这样，那么这些神经元中规则起搏和爆发模式之间的模式切换是如何调节的。在这项研究中，我们发现，仅对 TN-GnRH 神经元周围神经胶质的单个脉冲电刺激可重复性地诱导 TN-GnRH 神经元的短暂爆发活动。我们的生理和形态学综合数据表明，这种现象是由 TN-GnRH 神经元周围的胆碱能末梢介导的慢抑制性突触后电位引起的。我们还发现，毒蕈碱乙酰胆碱受体的激活诱导钾通道的持续开放，导致长时间的超极化。这种长时间的超极化诱导持续的反弹去极化，据认为这种反弹去极化是由持续的电压门控 Na(+)通道和低电压激活 Ca(2+)通道的组合产生的。这些新发现表明了一种新型的胆碱能调节肽能神经元爆发活动的方式，这应该有助于神经肽的释放。
