Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)).
GABA(B) (gamma-aminobutyric acid type B) receptors are important for keeping neuronal excitability under control. Cloned GABA(B) receptors do not show the expected pharmacological diversity of native receptors and it is unknown whether they contribute to pre- as well as postsynaptic functions. Here, we demonstrate that Balb/c mice lacking the GABA(B(1)) subunit are viable, exhibit spontaneous seizures, hyperalgesia, hyperlocomotor activity, and memory impairment. Upon GABA(B) agonist application, null mutant mice show neither the typical muscle relaxation, hypothermia, or delta EEG waves. These behavioral findings are paralleled by a loss of all biochemical and electrophysiological GABA(B) responses in null mutant mice. This demonstrates that GABA(B(1)) is an essential component of pre- and postsynaptic GABA(B) receptors and casts doubt on the existence of proposed receptor subtypes.
Schuler
V
V
Novartis Pharma AG, TA Nervous System, CH-4002, Basel, Switzerland.
Lüscher
C
C
Blanchet
C
C
Klix
N
N
Sansig
G
G
Klebs
K
K
Schmutz
M
M
Heid
J
J
Gentry
C
C
Urban
L
L
Fox
A
A
Spooren
W
W
Jaton
A L
AL
Vigouret
J
J
Pozza
M
M
Kelly
P H
PH
Mosbacher
J
J
Froestl
W
W
Käslin
E
E
Korn
R
R
Bischoff
S
S
Kaupmann
K
K
van der Putten
H
H
Bettler
B
B
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D001833:Body Temperature Regulation; D003700:Delta Rhythm / Q000187:drug effects; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology; D006930:Hyperalgesia / Q000235:genetics* / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits; D018080:Receptors, GABA-B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018755:GABA Agonists; D021122:Protein Subunits; D018080:Receptors, GABA-B; D001418:Baclofen