Deletion of Clock Gene () in Astrocytes Shortens Clock Period but Does Not Affect Light-Mediated Phase Shifts in Mice.

The circadian clock is a self-sustaining oscillator with a period of approximately 24 h, enabling organisms to anticipate daily recurring events, such as sunrise and sunset. Since the circadian period is not exactly 24 h and the environmental day length varies throughout the year, the clock must be periodically reset to align an organism's physiology with the natural light/dark cycle. This synchronization, known as entrainment, is primarily regulated by nocturnal light, which can be replicated in laboratory settings using a 15 min light pulse (LP) and by assessing locomotor activity. An LP during the early part of the dark phase delays the onset of locomotor activity, resulting in a phase delay, whereas an LP in the late dark phase advances activity onset, causing a phase advance. The clock gene () plays a key role in this process. To investigate its contributions, we examined the effects of deletion in neurons versus astrocytes using glia-specific (/) knockout (KO) and neuronal-specific KO (/) mice. All groups were subjected to Aschoff type II protocol, where an LP was applied at ZT14 or ZT22 and the animals were released into constant darkness. As control, no LP was applied. Phase shift, period, amplitude, total activity count, and rhythm instability were assessed. Our findings revealed that mice lacking in neurons () exhibited smaller phase delays and larger phase advances compared to control animals. In contrast, mice with deletion specifically in glial cells including astrocytes () displayed normal clock resetting. Interestingly, the absence of in either of the cell types resulted in a shorter circadian period compared to control animals. These results suggest that astrocytic is important for maintaining the circadian period but is not required for phase adaptation to light stimuli.