Altered development of glutamatergic synapses in layer V pyramidal neurons in NR3A knockout mice.
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, Mg2+-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 Mg2+ sensitivity than NR3A knockout (KO) mice and their reversal potential was approximately 2 mV more negative compared to KO mice consistent with decreased P(Ca) 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 Mg2+-insensitive NMDARs. The data indicate that NR3A plays a significant role in the development of excitatory synapses in layer V of the developing neocortex.
Department of Neurology, Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA.
Chengwen
C
Zhou
Frances E
FE
Jensen
Nikolaus J
NJ
Sucher
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
C464437:NR3A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D008274:Magnesium