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Journal of Neuroscience, Vol 5, 2909-2919, Copyright © 1985 by Society for Neuroscience
Distribution of N-methyl-D-aspartate-sensitive L-[3H]glutamate-binding sites in rat brain
DT Monaghan and CW Cotman
N-methyl-D-aspartate (NMDA) is an acidic amino acid which depolarizes
neurons by selectively interacting with a distinct class of excitatory
amino acid receptor. Recent evidence has indicated that this receptor is a
neurotransmitter receptor in the spinal cord, cerebral cortex, and
hippocampus for which the endogenous ligand is likely to be L-glutamate or
a structurally related compound. Using quantitative autoradiography, we
have studied the anatomical distribution of the class of L-
[3H]glutamate-binding sites displaced by NMDA, which appear to correspond
to NMDA receptors. The CA1 region of the hippocampus contains the highest
density of sites. In general, telencephalic regions have high levels of
binding sites. The cerebral cortex shows significant density variations
among the differing layers and regions, with the highest levels found in
the frontal cortex layers I to III. Within the basal ganglia, the highest
levels are found in the nucleus accumbens, intermediate levels are found in
the caudate/putamen, and very low levels are found in the globus pallidus.
Thalamic regions have moderate levels with variations among differing
regions. Midbrain and brainstem have low levels of binding sites, but
within these regions there are structures exhibiting higher levels, e.g.,
the nucleus of the solitary tract and the inferior olive. The distribution
of NMDA sites is consistent with most, but not all, of the regions
previously proposed to use glutamate as an excitatory transmitter. Thus,
the distribution of NMDA-sensitive L-[3H]glutamate-binding sites suggests
that the NMDA receptor represents a major, distinct subset of excitatory
amino acid receptors and indicates regions in which neurotransmission may
be mediated or modulated by this receptor.
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