Postnatal changes in the laminar and subcellular distribution of NMDA-R1 subunits in the cat visual cortex as revealed by immuno-electron microscopy

Although it is recognized that nearly all synapses in the cerebral cortex form postnatally, little is known about the emergence of molecules necessary to render these synapses functional. This study visualized the emergence of synaptically localized NMDA receptors by immuno-electron microscopic labeling of the receptor's obligatory subunit, NMDA-R1, in the developing cat visual cortex. Prior to eye-opening (postnatal day 2-10), NMDA-R1 immunoreactivity is already present within dendritic and axonal growth cones, even though these profiles are devoid of synaptic specializations. This indicates that synthesis and incorporation of NMDA-R1 into plasma membranes are independent of form vision. During the next 2-3 weeks, i.e., preceding the onset of the critical period for ocular dominance plasticity (around the fourth week), NMDA-R1 immunoreactivity changes from a diffuse distribution within dendrites to a more discrete aggregation over postsynaptic densities of axo-spinous junctions. Such clustering of NMDA-R1 at synapses may be a prerequisite for stabilization and strengthening of synapses activated by visual stimulation during the critical period. Furthermore, only during the first several weeks, intensely NMDA-R1-immunoreactive neurons are present in the infragranular layers and the white matter. Enrichment of NMDA-R1 in the deep-layer neurons may reflect the neurons' supportive role in the development of cortical circuitry, serving as transient synaptic targets for geniculate and cortico-cortical afferents while these afferents 'wait' in the infragranular layers for their ultimate, life-long target neurons to become receptive in the upper layers.