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The Journal of Neuroscience, July 1, 2002, 22(13):5572-5580

Enhanced Learning and Memory and Altered GABAergic Synaptic Transmission in Mice Lacking the 5 Subunit of the GABA_A Receptor

Neil Collinson^*, Frederick M. Kuenzi^*, Wolfgang Jarolimek^*, Karen A. Maubach^*, Rosa Cothliff^*, Cyrille Sur, Alison Smith, Franklin M. Otu, Owain Howell, John R. Atack, Ruth M. McKernan, Guy R. Seabrook, Gerry R. Dawson, Paul J. Whiting, and Thomas W. Rosahl

Neuroscience Research Center, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, CM20 2QR, United Kingdom

The 5 subunit of the GABA_A receptor is localized mainly to the hippocampus of the mammalian brain. The significance of this rather distinct localization and the function of 5-containing GABA_A receptors has been explored by targeted disruption of the 5 gene in mice. The 5 / mice showed a significantly improved performance in a water maze model of spatial learning, whereas the performance in non-hippocampal-dependent learning and in anxiety tasks were unaltered in comparison with wild-type controls. In the CA1 region of hippocampal brain slices from 5 / mice, the amplitude of the IPSCs was decreased, and paired-pulse facilitation of field EPSP (fEPSP) amplitudes was enhanced. These data suggest that 5-containing GABA_A receptors play a key role in cognitive processes by controlling a component of synaptic transmission in the CA1 region of the hippocampus.

Key words: GABA_A receptor; mouse; hippocampus; learning and memory; water maze; elevated plus maze; active avoidance; synaptic transmission; inhibitory postsynaptic current; paired pulse facilitation; long-term potentiation; benzodiazepine

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^* N.C., F.M.K., W.J., K.A.M., and R.C. contributed equally to different aspects of this work.

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22135572-09$05.00/0

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