Role of α2δ3 in Cellular Synchronization of the Suprachiasmatic Nucleus Under Constant Light Conditions

By the effort to identify candidate signaling molecules important for the formation of robust circadian rhythms in the suprachiasmatic nucleus (SCN), the mammalian circadian center, here we characterize the role of alpha 2 delta proteins, synaptic molecules initially identified as an auxiliary subunit of the voltage dependent calcium channel, in circadian rhythm formation. In situ hybridization study demonstrated that type 3 alpha 2 delta gene (alpha 2 delta 3) was strongly expressed in the SCN. Mice without this isoform (Cacn alpha 2 delta 3(-/-)) did not maintain proper circadian locomotor activity rhythms under a constant light (LL) condition, whereas under a constant dark (DD) condition, these mice showed a similar period length and similar light-responsiveness as compared to wild type mice. Reflecting this behavioral phenotype, Cacn alpha 2d delta(-/-) mice showed a severely impaired Per1 expression rhythm in the SCN under LL, but not under DD. Cultured SCN slices from Per1-luc transgenic Cacn alpha 2 delta 3(-/-) mice revealed reduced synchrony of Per1-luc gene expression rhythms among SCN neurons. These findings suggest that alpha 2 delta 3 is essential for synchronized cellular oscillations in the SCN and thereby contributes to enhancing the sustainability of circadian rhythms in behavior. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of IBRO.

Automated summary

The alpha 2 delta 3 protein plays a crucial role in synchronized cellular oscillations in the suprachiasmatic nucleus (SCN) and contributes to enhancing the sustainability of circadian rhythms in behavior. Mice lacking alpha 2 delta 3 showed severely impaired circadian locomotor activity rhythms under constant light conditions but exhibited normal behavior under constant dark conditions.