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Journal of Neuroscience, Vol 14, 5202-5222, Copyright © 1994 by Society for Neuroscience
Cellular and subcellular localization of NMDA-R1 subunit immunoreactivity in the visual cortex of adult and neonatal rats
C Aoki, C Venkatesan, CG Go, JA Mong and TM Dawson
Center for Neural Science, New York University, New York 10003.
NMDA receptor activation can alter synaptic strength, cause cell death, and
may modulate the release of glutamate and other neurotransmitters. Using a
specific and selective antiserum directed against the R1 subunit of the
NMDA receptor, we examined (1) whether NMDA receptors in the adult rat
visual cortex are exclusively postsynaptic or also presynaptic and (2)
whether NMDA-R1 subunits are incorporated into the plasma membrane prior
to, contemporaneously, or following the formation of synapses during
postnatal development. By light microscopy, NMDA-R1 immunoreactivity in the
adult visual cortex is easily detectable within perikarya and proximal
dendrites in laminae 2-6. Many of them have the morphological features of
pyramidal neurons. In addition, fine punctate labeling is evident
throughout the neuropil. Electron microscopy reveals these puncta to reside
at postsynaptic densities of axospinous junctions and at fine astrocytic
processes and axon terminals. In the deeper laminae, the majority of
labeled profiles are astrocytic. Visual cortices of animals in their first
postnatal week show concentrated immunoreactivity in a few nonpyramidal
neurons within laminae that have just differentiated from the cortical
plate. Electron microscopy reveals diffuse labeling along the plasma
membrane of dendritic shafts lacking morphologically identifiable synaptic
junctions or appositions to axons. Immunoreactivity is detectable in
dendritic processes by postnatal day (PND) 2, in axonal processes by PND 4,
and in astrocytic profiles by PND 14. Immunoreactivity also is detectable
along the postsynaptic membrane of presumably transient axosomatic
junctions. At all ages, the prevalence of NMDA-R1-immunoreactive profiles
is lamina 1 > 4/5 > 6/6B. These results provide the cellular basis
for NMDA receptors' participation in (1) postsynaptic membrane
excitability, (2) regulation of transmitter release, (3) and, in the deeper
laminae, astrocyte responses. During development, NMDA-R1 subunits are
associated with the plasma membrane prior to axons' arrival while
clustering of receptors to junctions may be promoted by axonal contact.
Finally, spatial segregation of axonal growth cones may be mediated by
NMDA-R1 subunits on these axonal processes.
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