Comprehensive behavioural study of GluR4 knockout mice: implication in cognitive function.
Fast excitatory transmission in the mammalian central nervous system is mediated by AMPA-type glutamate receptors. The tetrameric AMPA receptor complexes are composed of four subunits, GluR1-4. The GluR4 subunit is highly expressed in the cerebellum and the early postnatal hippocampus and is thought to be involved in synaptic plasticity and the development of functional neural circuitry through the recruitment of other AMPA receptor subunits. Previously, we reported an association of the human GluR4 gene (GRIA4) with schizophrenia. To examine the role of the GluR4 subunit in the higher brain function, we generated GluR4 knockout mice and conducted electrophysiological and behavioural analyses. The mutant mice showed normal long-term potentiation (LTP) in the CA1 region of the hippocampus. The GluR4 knockout mice showed mildly improved spatial working memory in the T-maze test. Although the retention of spatial reference memory was intact in the mutant mice, the acquisition of spatial reference memory was impaired in the Barnes circular maze test. The GluR4 knockout mice showed impaired prepulse inhibition. These results suggest the involvement of the GluR4 subunit in cognitive function.
Sagata
N
N
Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Iwaki
A
A
Aramaki
T
T
Takao
K
K
Kura
S
S
Tsuzuki
T
T
Kawakami
R
R
Ito
I
I
Kitamura
T
T
Sugiyama
H
H
Miyakawa
T
T
Fukumaki
Y
Y
D000161:Acoustic Stimulation; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007266:Inhibition, Psychological; D017774:Long-Term Potentiation / Q000235:genetics* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; D016291:Dizocilpine Maleate