Dissociating the Effects of Light at Night from Circadian Misalignment in a Neurodevelopmental Disorder Mouse Model Using Ultradian Light–Dark Cycles

Individuals with neurodevelopmental disorders (NDDs) often experience sleep disturbances and are frequently exposed to light during nighttime hours. Our previous studies using the <i>Contactin-associated protein-like 2</i> (<i>Cntnap2</i>) knockout (KO) mouse model of NDDs demonstrated that nighttime light exposure adversely affected behavioral measures. In this study, we exposed wild-type (WT) and <i>Cntnap2</i> KO mice to an ultradian lighting cycle (T7), which alternates 3.5 h of light and 3.5 h of darkness, hypothesizing that this lighting protocol would mimic the impact of nighttime light exposure seen in standard light-dark cycles with dim light at night (DLaN). However, adult WT and <i>Cntnap2</i> KO mice held under the T7 cycle did not show the increased grooming behavior or reduced social interaction observed in <i>Cntnap2</i> KO mice exposed to DLaN. The T7 cycle lengthened the circadian period and weakened the rhythm amplitude without abolishing rhythmicity in either genotype. Finally, opposite to DLaN, neither the T7 cycle nor constant darkness (DD) elicited an increase in cFos expression in the basolateral amygdala. These results demonstrate that the adverse effects of nighttime light exposure in an NDD model depend on the extent of the circadian disruption rather than light exposure alone, emphasizing the importance of circadian stability as a protective factor in NDDs.