Developmental Switch of Inhibitory Neurotransmitter from GABA to Glycine

点击翻译按钮获取中文摘要

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