Hippocampal α5, subunit-containing GABAAreceptors modulate the expression of prepulse inhibition

J. Hauser, U. Rudolph, R. Keist, H. Möhler, J. Feldon, Kay Yan Benjamin Yee

Research output: Journal article publicationJournal articleAcademic researchpeer-review

71 Citations (Scopus)

Abstract

Prepulse inhibition (PPI) refers to the phenomenon in which a low-intensity prepulse stimulus attenuates the reflexive response to a succeeding startle-eliciting pulse stimulus. The hippocampus, among other structures, is believed to play an important role in the modulation of PPI expression. In α5(H105R) mutant mice, the expression of the α5 subunit-containing GABAAreceptors in the hippocampus is reduced. Here, we report that PPI was attenuated, and spontaneous locomotor activity was increased in α5(H105R) mutant mice. These effects were apparent in both genders. Thus, α5 subunit-containing GABAAreceptors, which are located extrasynaptically and are thought to mediate tonic inhibition, are important regulators of the expression of PPI and locomotor exploration. Post-mortem analyses of schizophrenia brains have consistently revealed structural abnormalities of a developmental origin in the hippocampus. There may be a possibility that such abnormalities include disturbance of α5 GABAAreceptor function or distribution, given that schizophrenia patients are known to exhibit a PPI deficit. Our data further highlight that the potential use of α5-selective inverse agonists to treat hippocampal-related mnemonic dysfunction needs to be considered against the possibility that such compounds may be adversely associated with deficient sensorimotor gating.
Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalMolecular Psychiatry
Volume10
Issue number2
DOIs
Publication statusPublished - 1 Feb 2005
Externally publishedYes

Keywords

  • GABA receptors A
  • Hippocampus
  • Mice
  • Prepulse inhibition
  • Schizophrenia
  • Sensorimotor gating

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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