Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Endocrinology. 2018 Apr 1;159(4):1678-1689. doi: 10.1210/en.2017-03210.
Peptidergic neurons are suggested to play a key role in neuromodulation of animal behaviors in response to sensory cues in the environment. Terminal nerve gonadotropin-releasing hormone 3 (TN-GnRH3) neurons are thought to be one of the peptidergic neurons important for such neuromodulation in adult vertebrates. On the other hand, it has been reported that TN-GnRH3 neurons are labeled by a specific GnRH3 antibody from early developmental stages to adulthood and are thus suggested to produce mature GnRH3 peptide even in the early developmental stages. However, it remains unknown when TN-GnRH3 neurons show spontaneous burst firing, which is suggested to be involved in neuropeptide release. Using a whole-brain in vitro preparation of gnrh3:enhanced green fluorescent protein (EGFP) medaka fish, we first recorded spontaneous firings of TN-GnRH3 neurons after hatching to adulthood. Contrary to what one would expect from their neuromodulatory functions-that TN-GnRH3 neurons are more active in adulthood-TN-GnRH3 neurons in juveniles showed spontaneous burst firing more frequently than in adulthood (juvenile-specific burst firing). Ca2+ imaging of TN-GnRH3 neurons in juveniles may further suggest that juvenile-specific burst firing triggers neuropeptide release. Furthermore, juvenile-specific burst firing was suggested to be induced by blocking persistent GABAergic inhibition to the glutamatergic neurons, which leads to an increase in glutamatergic synaptic inputs to TN-GnRH3 neurons. The present study reports that peptidergic neurons show juvenile-specific burst firing involved in triggering peptide release and suggests that juvenile TN-GnRH3 neurons have novel functions, in addition to neuromodulation.
肽能神经元被认为在动物对环境中感觉线索的行为的神经调节中发挥关键作用。终端神经促性腺激素释放激素 3（TN-GnRH3）神经元被认为是成年脊椎动物中这种神经调节的重要肽能神经元之一。另一方面，据报道，TN-GnRH3 神经元在早期发育阶段到成年期都被特定的 GnRH3 抗体标记，因此被认为即使在早期发育阶段也能产生成熟的 GnRH3 肽。然而，目前尚不清楚 TN-GnRH3 神经元何时会表现出自发爆发性放电，这被认为与神经肽释放有关。使用 gnrh3：增强型绿色荧光蛋白（EGFP）斑马鱼的全脑体外培养物，我们首先记录了孵化后到成年期 TN-GnRH3 神经元的自发放电。与人们预期的 TN-GnRH3 神经元在成年期更活跃的神经调节功能相反——在青少年中，TN-GnRH3 神经元的自发爆发性放电比成年期更频繁（青少年特异性爆发性放电）。青少年 TN-GnRH3 神经元的 Ca2+ 成像可能进一步表明，青少年特异性爆发性放电会触发神经肽释放。此外，青少年特异性爆发性放电被认为是通过阻断持续的 GABA 能抑制谷氨酸能神经元而诱导的，这会导致谷氨酸能突触输入到 TN-GnRH3 神经元增加。本研究报告称，肽能神经元表现出涉及触发肽释放的青少年特异性爆发性放电，并表明青少年 TN-GnRH3 神经元具有除神经调节以外的新功能。
