Altered development of glutamatergic synapses in layer V pyramidal neurons in NR3A knockout mice

作者：Zhou Chengwen; Jensen Frances E^*; Sucher Nikolaus J

来源：Molecular and Cellular Neuroscience, 2009, 42(4): 419-426.

DOI：10.1016/j.mcn.2009.09.004

Expression of the NMDA receptor (NMDAR) subunit NR3A reaches its highest level in layer V of the developing rodent cortex during the second postnatal week, a peak period of synaptogenesis. Incorporation of NR3A leads to the formation of non-canonical, Mg(2+)-insensitive NMDARs, but it is not known whether they participate in synaptic transmission and maturation. Here we show that in the second postnatal week, layer V pyramidal neurons in the somatosensory cortex of wild type (WT) mice exhibited evoked excitatory postsynaptic currents (eEPSCs) with 3- to 6-fold lower Mg(2+) sensitivity than NR3A knockout (KO) mice and their reversal potential was similar to 2 mV more negative compared to KO mice consistent with decreased Pc of NMDARs. Surprisingly, ablation of NR3A also led to a 20-fold reduction of the ratio of AMPAR- to NMDAR-mediated eEPSC amplitudes in KO mice. Insertion of AMPARs at the synapses of layer V pyramidal neurons appears to be facilitated by the expression of Mg(2+)-insensitive NMDARs. The data indicate that NR3A plays a significant role in the development of excitatory synapses in layer V of the developing neocortex.

• 出版日期2009-11