GABAA, GABAC, and NMDA receptor subunit expression in the suprachiasmatic nucleus and other brain regions

Bruce F. O'Hara, Rozi Andretic, H. Craig Heller, Donald B. Carter, Thomas S. Kilduff

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Identification of the neurotransmitter receptor subtypes within the suprachiasmatic nuclei (SCN) will further understanding of the mechanism of the biological clock and may provide targets to manipulate circadian rhythms pharmacologically. We have focused on the ionotropic GABA and glutamate receptors because these appear to account for the majority of synaptic communication in the SCN. Of the 15 genes known to code for GABA receptor subunits in mammals we have examined the expression of 12 in the SCN, neglecting only the α6, γ3, and ρ{variant}2 subunits. Among glutamate receptors, we have focused on the five known genes coding for the NMDA receptor subunits, and two subunits which help comprise the kainate-selective receptors. Expression was characterized by Northern analysis with RNA purified from a large number of mouse SCN and compared to expression in the remaining hypothalamus, cortex and cerebellum. This approach provided a uniform source of RNA to generate many replicate blots, each of which was probed repeatedly. The most abundant GABA receptor subunit mRNAs in the SCN were α2, α5, β1, β3, γ1 and γ2. The ρ{variant}1 (rhol) subunit, which produces GABAC pharmacology, was expressed primarily in the retina in three different species and was not detectable in the mouse SCN despite a common embryological origin with the retina. For several GABA subunits we detected additional mRNA species not previously described. High expression of both genes coding for glutamic acid decarboxylase (GAD65 and GAD67) was also found in the SCN. Among the NMDA receptor subunits, NR1 was most highly expressed in the SCN followed in order of abundance by NR2B, NR2A, NR2C and NR2D. In addition, both GluR5 and GluR6 show clear expression in the SCN, with GluR5 being the most SCN specific. This approach provides a simple measure of receptor subtype expression, complements in situ hybridization studies, and may suggest novel isoforms of known subunits.

Original languageEnglish
Pages (from-to)239-250
Number of pages12
JournalMolecular Brain Research
Volume28
Issue number2
DOIs
StatePublished - Feb 1995

Keywords

  • Biological clock
  • Circadian rhythm
  • Glutamate decarboxylase
  • Northern analysis
  • Rho
  • mRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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