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A Developmental Switch of AMPA Receptor Subunits in Neocortical Pyramidal Neurons

AMPA receptors mediate most of the fast excitatory neurotransmission in the brain, and those lacking the glutamate receptor 2 (GluR2) subunit are Ca2+-permeable and expressed in cortical structures primarily by inhibitory interneurons. Here we report that synaptic AMPA receptors of excitatory layer 5 pyramidal neurons in the rat neocortex are deficient in GluR2 in early development, approximately before postnatal day 16, as evidenced by their inwardly rectifying current–voltage relationship, blockade of AMPA receptor-mediated EPSCs by external and internal polyamines, permeability to Ca2+, and GluR2 immunoreactivity. Overall, these results indicate that neocortical pyramidal neurons undergo a developmental switch in the Ca2+permeability of their AMPA receptors through an alteration of their subunit composition. This has important implications for plasticity and neurotoxicity.