Allaire P, Ikonomov O, Garrett M K, Jacob M H
Blackstone-Millville Regional High School, 175 Lincoln Street, Blackstone, MA 01504, USA.
Neuropharmacology. 2000 Oct;39(13):2691-8. doi: 10.1016/s0028-3908(00)00154-4.
Our recent studies of chick parasympathetic ciliary ganglion (CG) neurons demonstrate a unique postsynaptic receptor microheterogeneity - under one presynaptic terminal, excitatory nicotinic acetylcholine receptor (nAChR) clusters and separate inhibitory glycine receptor (GlyR) clusters coexist in distinct membrane microregions. Gephyrin, a peripheral membrane protein that is required for GlyR clustering at synapses in the rodent central nervous system, is also expressed in chick CG neurons where it codistributes with GlyRs, but not nAChRs. We now extend these findings by characterizing the regulation of gephyrin expression in chick CG neurons in vivo. We show that developmental increases in gephyrin transcript levels occur during pre- and postganglionic synapse formation. The increases are induced by both innervation and target tissue interactions, with the target tissues having the greater regulatory influence. The time course of the developmental rise in gephyrin mRNA levels most closely resembles that reported for functional GlyR expression, but not that of functional nAChRs nor GABA(A) receptors. We also demonstrate that gephyrin is concentrated in the postsynaptic density of a subset of synapses on both the ciliary and choroid neurons in the CG and is stably expressed from embryonic to adult stages. Altogether, our results suggest that gephyrin is a synapse organizing molecule that functions to localize GlyRs, but not nAChRs, to discrete postsynaptic membrane microregions in chick CG neurons in vivo.
我们最近对鸡副交感神经睫状神经节（CG）神经元的研究表明，其具有独特的突触后受体微异质性——在一个突触前终末下，兴奋性烟碱型乙酰胆碱受体（nAChR）簇和单独的抑制性甘氨酸受体（GlyR）簇共存于不同的膜微区。桥连蛋白是一种外周膜蛋白，在啮齿动物中枢神经系统的突触中，它是GlyR聚集所必需的，在鸡CG神经元中也有表达，且与GlyR共分布，但不与nAChR共分布。我们现在通过描述鸡CG神经元中桥连蛋白表达的体内调节机制来扩展这些发现。我们发现，在节前和节后突触形成过程中，桥连蛋白转录水平在发育过程中升高。这种升高是由神经支配和靶组织相互作用共同诱导的，其中靶组织具有更大的调节作用。桥连蛋白mRNA水平发育性升高的时间进程与报道的功能性GlyR表达最为相似，但与功能性nAChR或GABA(A)受体的时间进程不同。我们还证明，桥连蛋白集中在CG中睫状神经元和脉络膜神经元突触子集的突触后致密区，并且从胚胎期到成年期都稳定表达。总之，我们的结果表明，桥连蛋白是一种突触组织分子，其功能是在体内将GlyR而非nAChR定位到鸡CG神经元离散的突触后膜微区。
