Developmental Switch of Inhibitory Neurotransmitter from GABA to Glycine

在发育后期，中枢神经系统发生广泛的突触重排。关于这些突触重排，广泛传播的突触连接丢失、所谓的突触消除和突触功能的重塑已经被深入研究。关于突触功能的发育性变化，在突触后受体方面已有大量的报道，如受体亚基的变化、插入和内化等。本文首次报道了发育中突触重塑的一种新形式，即在发育中的听觉系统中，一种递质本身可以被转换，在成年大鼠的脑干中，外侧上级橄榄核（lateral superior olive，LSO）接受来自斜方体内侧核（medial nucleus of trapezoidal body，NMTB）的甘氨酸能传入。然而，在未成熟大鼠中，在听力发作之前，来自NMTB-LSO的传入主要是GABA能的。开发中 ...更多信息 NT，NMTB-LSO突触由GABA能变为甘氨酸能。微型突触电流分析表明，共同释放的GABA和甘氨酸从NMTB突触的特点是在短暂的发展时期。电镜观察和免疫组化研究表明，在发育的前两周，终末的递质逐渐由GABA转变为甘氨酸。因此，这些结果提出了在单个突触终末内递质本身可能发生变化的可能性。为了揭示这种递质从GABA转换为甘氨酸的可能机制，我们重点研究了GABA-B受体的发育变化。在未成熟的LSO神经元中，存在GABA-B受体的密集表达。在发育过程中，LSO神经元中GABA-B受体表达消失。此外，GABA-B介导的K+电流和GABA/甘氨酸突触的长时程抑制在LSO中逐渐消失。因此，从GABA到甘氨酸释放的发育转换可能导致突触调节的逐渐丧失，并通过甘氨酸能传递获得坚实而快速的突触传递。少

In the late stage of development, a wide spread of synapses re-arrangement take place on the central nervous system. Regarding to these synapse re-arrangements, a wide spread of loss of synapse connection, so-call synapse elimination and a remodeling of synaptic function have been intensely studied. As for developmental change of synaptic function, a large amount of evidences have been reported in the post-synaptic receptors, e.g. subunits changes, and insertion and internalization of receptors. Here, we first reports a new from of remodeling in the developing synapses that a transmitter itself could be switched in the developing auditory system.The lateral superior olive (LSO), an auditory relay center in the brain stem and involved in the orientation of direction of sound coming, receives glycinergic afferents from medial nucleus of trapezoid body (NMTB), in mature rats. However, in immature rats, before onset of hearing, the afferents from NMTB-LSO are largely GABAergic. In developm … More ent, NMTB-LSO synapse changes from GABAergic to glycinergic. Miniature synaptic current analyses revealed that co-release of GABA and glycine from NMTB synapses are well characterized at the transient period of developments. In addition, electron microscopic examination and immunohistochemical study showed that the the transmitter in the terminal gradually changed from GABA to glycine in the first two weeks in development. Thus, these results raise the possibility that the transmitter itself could be change within a single synaptic terminal.For revealing the possible mechanism for this transmitter switch from GABA to glycine, we focused on the developmental change in GABA-B receptors. In immature LSO neurons, there is a dense expression of GABA-B receptor. In development, GABA-B receptor expression disappeared in the LSO neurons. In addition, GABA-B mediated K+ currents and long term depression of GABA/glyicine synapses gradually disappeared in the LSO. Thus, the developmental switch from GABA to glycine release might lead to gradual loss of synapse modulation, and acquirement of solid and fast synaptic transmission by using glycinergic transmission. Less