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Hippocampal α5 subunit-containing GABAA receptors modulate the expression of prepulse inhibition

Molecular Psychiatry volume 10, pages 201–207 (2005)Cite this article

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 GABAA receptors 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 GABAA receptors, 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 GABAA receptor 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.

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Acknowledgements

This study was supported by the Swiss Federal Institute of Technology Zurich. BK Yee received additional support from the NCCR: Neural Plasticity and Repair, Swiss National Science Foundation. We thank Mr Peter Schmid for his technical expertise, and Ms Misa Kuper-Yamanaka for her editorial assistance. We remain also indebted to Jeanne von Arx and Pascal Guela for their care of the animals and to Dr Frank Bootz for his veterinary supervision.

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Authors and Affiliations

  1. Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schwerzenbach, Switzerland

    J Hauser, J Feldon & B K Yee

  2. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

    U Rudolph, R Keist & H Möhler

  3. Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

    H Möhler

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  1. J Hauser
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  2. U Rudolph
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Correspondence to B K Yee.

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Hauser, J., Rudolph, U., Keist, R. et al. Hippocampal α5 subunit-containing GABAA receptors modulate the expression of prepulse inhibition. Mol Psychiatry 10, 201–207 (2005). https://doi.org/10.1038/sj.mp.4001554

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