Segregation of different GABA(A) receptors to synaptic and extrasynaptic membranes of cerebellar granule cells

Z. Nusser, Werner Sieghart, Peter Somogyi

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Abstract

Two types of GABA(A) receptor-mediated inhibition (phasic and tonic) have been described in cerebellar granule cells, although these cells receive GABAergic input only from a single cell type, the Golgi cell. In adult rats, granule cells express six GABA(A) receptor subunits abundantly (α1, α6, β2, β3, γ2, and δ), which are coassembled into at least four to six distinct GABA(A) receptor subtypes. We tested whether a differential distribution of GABA(A) receptors on the surface of granule cells could play a role in the different forms of inhibition, assuming that phasic inhibition originates from the activation of synaptic receptors, whereas tonic inhibition is provided mainly by extrasynaptic receptors. The α1, α6, β2/3, and γ2 subunits have been found by immunogold localizations to be concentrated in GABAergic Golgi synapses and also are present in the extrasynaptic membrane at a lower concentration. In contrast, immunoparticles for the δ subunit could not be detected in synaptic junctions, although they were abundantly present in the extrasynaptic dendritic and somatic membranes. Gold particles for the α6, γ2, and β2/3, but not the α1 and δ, subunits also were concentrated in some glutamatergic mossy fiber synapses, where their colocalization with AMPA-type glutamate receptors was demonstrated. The exclusive extrasynaptic presence of the δ subunit-containing receptors, together with their kinetic properties, suggests that tonic inhibition could be mediated mainly by extrasynaptic α6β(2/3)δ receptors, whereas phasic inhibition is attributable to the activation of synaptic α1/β(2/3)γ2, α6β(2/3)γ2, and α1α6β(2/3)γ2 receptors.

Original languageEnglish
Pages (from-to)1693-1703
Number of pages11
JournalJournal of Neuroscience
Volume18
Issue number5
Publication statusPublished - Mar 1 1998

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Synaptic Membranes
GABA-A Receptors
Synapses
Neurotransmitter Receptor
AMPA Receptors
Membranes
Glutamate Receptors
Gold

Keywords

  • Cerebellum
  • Immunocytochemistry
  • Inhibition
  • Ion channel
  • Neurotransmission
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Segregation of different GABA(A) receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. / Nusser, Z.; Sieghart, Werner; Somogyi, Peter.

In: Journal of Neuroscience, Vol. 18, No. 5, 01.03.1998, p. 1693-1703.

Research output: Contribution to journalArticle

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