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The Journal of Neuroscience, July 30, 2003, 23(17):6793-6797

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BRIEF COMMUNICATION
N-Type Calcium Channel _1B Subunit (Ca_V2.2) Knock-Out Mice Display Hyperactivity and Vigilance State Differences

Carsten T. Beuckmann,^1,2,4 Christopher M. Sinton,³ Norimasa Miyamoto,^1,4 Mitsuhiro Ino,¹ and Masashi Yanagisawa^2,4

¹Eisai Company Ltd., Tsukuba, 300-2635 Ibaraki, Japan, and ²Howard Hughes Medical Institute and Departments of ³Internal Medicine and ⁴Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Differential properties of voltage-dependent Ca²⁺ channels have been primarily ascribed to the ₁ subunit, of which 10 different subtypes are currently known. For example, channels that conduct the N-type Ca²⁺ current possess the _1B subunit (Ca_v2.2), which has been localized, inter alia, to the piriform cortex, hippocampus, hypothalamus, locus coeruleus, dorsal raphe, thalamic nuclei, and granular layer of the cortex. Some of these regions have been previously implicated in metabolic and vigilance state control, and selective block of the N-type Ca²⁺ channel causes circadian rhythm disruption. In this study of Ca_v2.2^-/- knock-out mice, we examined potential differences in feeding behavior, spontaneous locomotion, and the sleep-wake cycle. Ca_v2.2^-/- mice did not display an overt metabolic phenotype but were hyperactive, demonstrating a 20% increase in activity under novel conditions and a 95% increase in activity under habituated conditions during the dark phase, compared with wild-type littermates. Ca_v2.2^-/- mice also displayed vigilance state differences during the light phase, including increased consolidation of rapid-eye movement (REM) sleep and increased intervals between non-REM (NREM) and wakefulness episodes. EEG spectral power was increased during wakefulness and REM sleep and was decreased during NREM sleep in Ca_v2.2^-/- mice. These results indicate a role of the N-type Ca²⁺ channel in activity and vigilance state control, which we interpret in terms of effects on neurotransmitter release.

Key words: mouse; calcium; locomotion; REM sleep; vigilance state; electroencephalogram; EEG

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Received Apr. 3, 2003; revised May. 19, 2003; accepted May. 22, 2003.

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