GABA and synaptic inhibition of mouse cerebellum lacking glutamate decarboxylase 67.
gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter and also presumed to be a neurotrophic factor. GABA is synthesized by glutamate decarboxylase (GAD). A mouse lacking a 67kDa isoform of GAD (GAD67) has a reduced GABA level in its brain at birth and does not survive postnatally because of cleft palate. In this study, to investigate the functional and developmental roles of GABA in the postnatal cerebellum, selective GAD67 deletion was achieved using a Cre-loxP strategy. In this mouse, GABA level was reduced to 16-44% in the cerebellum but not in the cerebrum. Inhibitory synaptic transmission to Purkinje cells was seriously impaired. However, the morphology of Purkinje cells and the density of synaptic terminals in the cerebellar cortex appeared unaffected, suggesting that GABA does not participate in cerebellar development substantially.
Obata
Kunihiko
K
Obata Research Unit, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama-ken 351-0198, Japan. obak@e-fumi.net
Hirono
Moritoshi
M
Kume
Nobuko
N
Kawaguchi
Yoshiya
Y
Itohara
Shigeyoshi
S
Yanagawa
Yuchio
Y
D000818:Animals; D002531:Cerebellum / Q000201:enzymology* / Q000254:growth & development; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011689:Purkinje Cells / Q000201:enzymology / Q000502:physiology; D017384:Sequence Deletion; D013569:Synapses / Q000201:enzymology*; D009435:Synaptic Transmission / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000172:deficiency* / Q000235:genetics
D014157:Transcription Factors; C062602:transcription factor PTF1; D005680:gamma-Aminobutyric Acid; C045073:Cre recombinase; D019426:Integrases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1