Rostas J A, Kavanagh J M, Dodd P R, Heath J W, Powis D A
Faculty of Medicine, University of Newcastle, Callaghan, N.S.W., Australia.
Mol Neurobiol. 1991;5(2-4):203-16. doi: 10.1007/BF02935546.
We have shown that the synapse maturation phase of synaptogenesis is a model for synaptic plasticity that can be particularly well-studied in chicken forebrain because for most forebrain synapses, the maturation changes occur slowly and are temporally well-separated from the synapse formation phase. We have used the synapse maturation phase of neuronal development in chicken forebrain to investigate the possible link between changes in the morphology and biochemical composition of the postsynaptic density (PSD) and the functional properties of glutamate receptors overlying the PSD. Morphometric studies of PSDs in forebrains and superior cervical ganglia of chickens and rats have shown that the morphological features of synapse maturation are characteristic of a synaptic type, but that the rate at which these changes occur can vary between types of synapses within one animal and between synapses of the same type in different species. We have investigated, during maturation in the chicken forebrain, the properties of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors, which are concentrated in the junctional membranes overlying thick PSDs in the adult. There was no change in the number of NMDA receptors during maturation, but there was an increase in the rate of NMDA-stimulated uptake of 45Ca2+ into brain prisms. This functional change was not seen with the other ionotropic subtypes of the glutamate receptor and was NMDA receptor-mediated. The functional change also correlated with the increase in thickness of the PSD during maturation that has previously been shown to be due to an increase in the amount of PSD associated Ca(2+)-calmodulin stimulated protein kinase II (CaM-PK II). Our results provide strong circumstantial evidence for the regulation of NMDA receptors by the PSD and implicate changing local concentrations of CaM-PK II in this process. The results also indicate some of the ways in which properties of existing synapses can be modified by changes at the molecular level.
我们已经表明，突触发生的突触成熟阶段是突触可塑性的一个模型，在鸡前脑中可以得到特别好的研究，因为对于大多数前脑突触来说，成熟变化发生缓慢，并且在时间上与突触形成阶段有很好的分离。我们利用鸡前脑神经元发育的突触成熟阶段来研究突触后致密部（PSD）的形态和生化组成变化与PSD上谷氨酸受体功能特性之间的可能联系。对鸡和大鼠前脑及颈上神经节中PSD的形态测量研究表明，突触成熟的形态特征是突触类型所特有的，但这些变化发生的速率在同一动物体内的不同突触类型之间以及不同物种中同一类型的突触之间可能有所不同。我们在鸡前脑成熟过程中研究了谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型的特性，该亚型在成体中集中在覆盖厚PSD的连接膜中。成熟过程中NMDA受体的数量没有变化，但NMDA刺激的45Ca2+摄取到脑棱镜中的速率有所增加。这种功能变化在谷氨酸受体其他离子型亚型中未观察到，是由NMDA受体介导的。这种功能变化也与成熟过程中PSD厚度的增加相关，此前已表明这是由于与PSD相关的钙调蛋白依赖性蛋白激酶II（CaM-PK II）量的增加所致。我们的结果为PSD对NMDA受体的调节提供了有力的间接证据，并暗示在此过程中CaM-PK II局部浓度的变化。结果还表明了现有突触特性可以通过分子水平的变化进行修饰的一些方式。
