Mouse cerebellar granule cell differentiation: Electrical activity regulates the GABA(A) receptor α6 subunit gene

J. R. Mellor, D. Merlo, A. Jones, W. Wisden, A. D. Randall

Research output: Contribution to journalArticlepeer-review

Abstract

GABA(A) receptor α6 subunit gene expression marks cerebellar granule cell maturation. To study this process, we used the Δα6lacZ mouse line, which has a lacZ reporter inserted into the α6 gene. At early stages of postnatal cerebellar development, α6-lacZ expression is mosaic; expression starts at postnatal day 5 in lobules 9 and 10, and α6-lacZ is switched on inside-out, appearing first in the deepest postmigratory granule cells. We looked for factors regulating this expression in cell culture. Membrane depolarization correlates inversely with α6-lacZ expression: granule cells grown in 25 mM [K+](o) for 11-15 d do not express the α6 gene, whereas cultures grown for the same period in 5 mM [K+](o) do. This is influenced by a critical early period: culturing for ≤3 d in 25 mM [K+](o) curtails the ability to induce the α6 gene on transfer to 5 mu [K+](o). If the cells start in 5 mM [K+](o), however, they still express the α6-lacZ gene in 25 mM [K+](o). In contrast to granule cells grown in 5 mM [K+](o), cells cultured in 25 mM [K+](o) exhibit no action potentials, mEPSCs, or mIPSCs. In chronic 5 mM [K+](o), factors may therefore be released that induce α6. Blockade of ionotropic and metabotropic GABA and glutamate receptors or L-, N-, and P/Q-type Ca2+ channels did not prevent α6-lacZ expression, but inhibition of action potentials with tetrodotoxin blocked expression in a subpopulation of cells.

Original languageEnglish
Pages (from-to)2822-2833
Number of pages12
JournalJournal of Neuroscience
Volume18
Issue number8
Publication statusPublished - Apr 15 1998

Keywords

  • β-galactosidase reporter genes
  • Action potentials
  • Cell culture
  • Cerebellum
  • Differentiation
  • Electrophysiology
  • GABA(A) receptor subunit
  • Granule cell
  • Internal ribosome entry site
  • Membrane depolarization
  • Neuron-specific gene expression
  • Tetrodotoxin
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

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