Lack of delta waves and sleep disturbances during non-rapid eye movement sleep in mice lacking alpha 1(G)-subunit of T-type calcium channels

Abstract

T-type calcium channels have been implicated as a pacemaker for brain rhythms during sleep but their contribution to behavioral states of sleep has been relatively uncertain. Here, we found that mice lacking alpha1(G) T-type Ca2+ channels showed a loss of the thalamic delta (1-4 Hz) waves and a reduction of sleep spindles (7-14 Hz), whereas slow (< 1 Hz) rhythms were relatively intact, when compared with the wild-type during urethane anesthesia and non-rapid eye movement (NREM) sleep. Analysis of sleep disturbances, as defined by the occurrence of brief awakening (BA) episodes during NREM sleep, revealed that mutant mice exhibited a higher incidence of BAs of > 16 sec compared with the wild-type, whereas no difference was seen in BAs of < 16 sec between the two genotypes. These results are consistent with the previous idea of the distinct nature of delta oscillations and sleep spindles from cortically generated slow waves. These results also suggest that the alpha1(G)-subunit of T-type calcium channels plays a critical role in the genesis of thalamocortical oscillations and contributes to the modulation of sleep states and the transition between NREM sleep and wake states.