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Journal of Neuroscience, Vol 14, 3180-3194, Copyright © 1994 by Society for Neuroscience
Regional and developmental heterogeneity in splicing of the rat brain NMDAR1 mRNA
DJ Laurie and PH Seeburg
Laboratory of Molecular Neurobiology, University of Heidelberg, Germany.
Developmental and regional alternative splicing of the NMDAR1 subunit gene
transcript was examined by in situ hybridization in the developing and
adult rat brain. NMDAR1 mRNA, barely detectable at embryonic day 14,
increased gradually during development until the third postnatal week,
after which it declined slightly to adult levels, when it was detected in
every examined neuronal type. Each splice form of the primary NMDAR1 gene
transcript was found to follow a parallel profile of abundance in the
brain, but marked regional differences were observed in splicing at both 5'
and 3' sequences. The individual regional distributions of splice forms
appeared to be established around birth, with little change thereafter,
except in the overall abundance. The NMDAR1-a and NMDAR1-2 splice forms
occurred extensively and approximately homogeneously throughout brain gray
matter. The NMDAR1-b variant was found primarily in the sensorimotor
cortex, neonatal lateral caudate, thalamus, hippocampal CA3 field, and
cerebellar granule cells, but was absent from adult caudate. The NMDAR1- 1
and -4 splice forms were detected in almost complementary patterns; the
former was concentrated in more rostral structures such as cortex, caudate,
and hippocampus, while the latter was principally in more caudal regions
such as thalamus, colliculi, and cerebellum. These two splice forms
accounted for a greater proportion of the adult NMDAR1 mRNA than that of
the neonate. The NMDAR1-3 mRNA variant was scarce, being detected only at
very low levels in postnatal cortex and hippocampus. The different splice
forms may generate regional differences in NMDA receptor properties during
development and in the adult CNS.
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