Involvement of GluD2 in Fear-Conditioned Bradycardia in Mice.
Lesions in the cerebellar vermis abolish acquisition of fear-conditioned bradycardia in animals and human patients. The δ2 glutamate receptor (GluD2) is predominantly expressed in cerebellar Purkinje cells. The mouse mutant ho15J carries a spontaneous mutation in GluD2 and these mice show a primary deficiency in parallel fiber-Purkinje cell synapses, multiple innervations of Purkinje cells by climbing fibers, and impairment of long-term depression. In the present study, we used ho15J mice to investigate the role of the cerebellum in fear-conditioned bradycardia. We recorded changes in heart rate of ho15J mice induced by repeated pairing of an acoustic (conditioned) stimulus (CS) with an aversive (unconditioned) stimulus (US). The mice acquired conditioned bradycardia on Day 1 of the CS-US phase, similarly to wild-type mice. However, the magnitude of the conditioned bradycardia was not stable in the mutant mice, but rather was exaggerated on Days 2-5 of the CS-US phase. We examined the effects of reversibly inactivating the cerebellum by injection of an antagonist against the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR). The antagonist abolished expression of conditioned responses in both wild-type and ho15J mice. We conclude that the GluD2 mutation in the ho15J mice affects stable retention of the acquired conditioned bradycardia.
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo, Japan.
Hiroko
H
Kotajima-Murakami
Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Sakae
S
Narumi
Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Michisuke
M
Yuzaki
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo, Japan.
Dai
D
Yanagihara
D000818:Animals; D001919:Bradycardia / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003213:Conditioning, Psychological / Q000502:physiology*; D005239:Fear; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2