Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABAA receptor.
The alpha5 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 alpha5-containing GABA(A) receptors has been explored by targeted disruption of the alpha5 gene in mice. The alpha5 -/- 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 alpha5 -/- mice, the amplitude of the IPSCs was decreased, and paired-pulse facilitation of field EPSP (fEPSP) amplitudes was enhanced. These data suggest that alpha5-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.
Collinson
Neil
N
Neuroscience Research Center, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, CM20 2QR, United Kingdom.
Kuenzi
Frederick M
FM
Jarolimek
Wolfgang
W
Maubach
Karen A
KA
Cothliff
Rosa
R
Sur
Cyrille
C
Smith
Alison
A
Otu
Franklin M
FM
Howell
Owain
O
Atack
John R
JR
McKernan
Ruth M
RM
Seabrook
Guy R
GR
Dawson
Gerry R
GR
Whiting
Paul J
PJ
Rosahl
Thomas W
TW
D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D004553:Electric Conductivity; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D007858:Learning; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid