title: Behavioral and neurochemical characterization of mice deficient in the N-type Ca2+ channel alpha1B subunit.
abstract: N-type voltage-dependent calcium channels (VDCCs) play an important role in neurotransmission, synaptic plasticity, and brain development. They are composed of several subunits named alpha(1), alpha(2), delta, beta and gamma. The alpha(1) subunit is essential for channel functions and determines fundamental channel properties. Since N-type VDCC are critically involved in the release of neurotransmitters and clinical relevance, we predicted that alpha(1) subunit KO mice would show several alterations in behavior. In the present study, we investigated neuronal functions in mice lacking the alpha(1B) (Ca(V)2.2) subunit of the N-type calcium channels. Ca(V)2.2(-/-) mice exhibited a significant increase in locomotion on an activity wheel during the dark phase. Furthermore, when challenged with apomorphine, mutant mice showed enhanced locomotor activity. Cognitive functions were examined using a Y-maze task for short-term memory and a passive avoidance task for long-term memory. The Y-maze revealed no differences in spontaneous alternation behavior between mutant and wild-type mice. The passive avoidance test revealed that the latency time in mutant mice was significantly decreased. The mutant mice showed prepulse inhibition deficits reminiscent of the sensorimotor gating deficits observed in a large majority of schizophrenic patients. Decreases in baseline levels of dopamine and serotonin within the striata and frontal cortices of mutant mice were also observed. These results suggest that Ca(2+) in the central nervous system modulates various neurophysiological functions, such as locomotor activity, long-term memory, and sensorimotor gating through the alpha(1B) subunit of the N-type calcium channels.
authors: Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. osamun@tohoku-pharm.ac.jp
authors: Osamu
authors: O
authors: Nakagawasai
authors: Hiroshi
authors: H
authors: Onogi
authors: Satoru
authors: S
authors: Mitazaki
authors: Atsushi
authors: A
authors: Sato
authors: Kenya
authors: K
authors: Watanabe
authors: Hiroko
authors: H
authors: Saito
authors: Shigeo
authors: S
authors: Murai
authors: Kota
authors: K
authors: Nakaya
authors: Manabu
authors: M
authors: Murakami
authors: Eiki
authors: E
authors: Takahashi
authors: Koichi
authors: K
authors: Tan-No
authors: Takeshi
authors: T
authors: Tadano
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000172:deficiency*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002940:Circadian Rhythm / Q000235:genetics; D018491:Dopamine Agonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D007266:Inhibition, Psychological; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics; D045442:Rotarod Performance Test / Q000379:methods
chemical_list: D015306:Biogenic Monoamines; C500963:Cacna1b protein, mouse; D020864:Calcium Channels, N-Type; D018491:Dopamine Agonists; D001058:Apomorphine