Heinen K, Bosman L W J, Spijker S, van Pelt J, Smit A B, Voorn P, Baker R E, Brussaard A B
Department of Experimental Neurophysiology, Research Institute Neurosciences, Centre for Neurogenomics and Cognitive Research, Vrije Universiteit, Faculty of Earth and Life Sciences, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
Neuroscience. 2004;124(1):161-71. doi: 10.1016/j.neuroscience.2003.11.004.
Changes in subunit composition of N-methyl-D-aspartate (NMDA) receptors have been reported to be affected by visual experience and may therefore form a major aspect of neuronal plasticity in the CNS during development. In contrast, putative alterations in the expression and functioning of the inhibitory GABAA receptor around eye opening have not been well defined yet. Here we describe the timing of changes in GABAA receptor subunit expression and the related synaptic functioning in the neonatal rat visual cortex and the influence of visual experience on this process. Quantitative analysis of all GABAA receptor subunit transcripts revealed a marked alpha3 to alpha1 subunit switch, in addition to a change in alpha4 and alpha5 expression. The changes were correlated with an acceleration of the decay of spontaneous inhibitory postsynaptic currents (sIPSCs). Both changes in receptor expression and synaptic functioning were initiated well before eye opening. Moreover, dark rearing could not prevent the robust upregulation of alpha1 or the change in sIPSC kinetics, indicating that this is not dependent of sensory (visual) input. Upon eye opening a positive correlation was observed between a faster decay of the sIPSCs and an increase in sIPSC frequency, which was absent in dark-reared animals. Thus, lack of extrinsic input to the cortex does not affect overall developmental regulation of synaptic functioning of GABAA receptors. However, we cannot exclude the possibility that visual experience is involved in proper shaping of the inhibitory network of the primary visual cortex.
据报道，N-甲基-D-天冬氨酸（NMDA）受体亚基组成的变化受视觉经验影响，因此可能构成中枢神经系统发育过程中神经元可塑性的一个主要方面。相比之下，睁眼前后抑制性γ-氨基丁酸A（GABAA）受体表达和功能的假定变化尚未得到明确界定。在此，我们描述了新生大鼠视觉皮层中GABAA受体亚基表达变化的时间及其相关的突触功能，以及视觉经验对这一过程的影响。对所有GABAA受体亚基转录本的定量分析显示，除了α4和α5表达变化外，还存在明显的α3到α1亚基转换。这些变化与自发性抑制性突触后电流（sIPSCs）衰减加速相关。受体表达和突触功能的变化在睁眼之前就已开始。此外，暗饲养并不能阻止α1的强烈上调或sIPSC动力学的变化，这表明这并不依赖于感觉（视觉）输入。睁眼后，观察到sIPSCs更快衰减与sIPSC频率增加之间存在正相关，而暗饲养动物中不存在这种情况。因此，缺乏向皮层的外部输入并不影响GABAA受体突触功能的整体发育调节。然而，我们不能排除视觉经验参与初级视觉皮层抑制性网络正常塑造的可能性。
