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NMDA Receptor Stimulation Selectively Initiates GABA A Receptor δ Subunit mRNA Expression in Cultured Rat Cerebellar Granule Neurons
Author(s) -
Gault Laura M.,
Siegel Ruth E.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70051907.x
Subject(s) - nmda receptor , biology , protein subunit , glutamate receptor , microbiology and biotechnology , cerebellum , messenger rna , depolarization , receptor , neuroscience , endocrinology , biochemistry , gene
Findings in vivo and in culture suggest that neuronal activity selectively regulates GABA A receptor δ subunit mRNA expression in cerebellar granule neurons. For example, the onset of δ subunit mRNA expression during postnatal maturation coincides with innervation. Furthermore, depolarizing conditions (25 m M KCl) in culture initiate and maintain increases in the δ subunit transcript level. We have now examined whether similar changes in δ subunit mRNA expression occur in cultured neurons after activation of glutamate receptors of the NMDA subtype, an event that mimics granule neuron depolarization by mossy fiber innervation in vivo. Our studies demonstrate that addition of 50 µ M NMDA to cultured rat granule neurons maintained in defined, serum‐free medium specifically initiates δ subunit transcript expression. Whereas the level of the δ subunit mRNA is increased fourfold by this treatment, levels of other GABA A receptor subunit transcripts are not significantly changed. The level of the δ subunit transcript is further increased when NMDA receptor activation is enhanced by maintaining neurons in a Mg 2+ ‐free medium to alleviate Mg 2+ blockade of the receptor channel. The NMDA‐induced elevation in δ subunit transcript expression involves activation of a Ca 2+ /calmodulin‐dependent protein kinase pathway. These findings suggest that activation of an excitatory pathway may regulate the expression of an inhibitory receptor phenotype in cerebellar granule neurons in vivo.