The habenula clock in zebrafish underlies circadian variation in response to a stressor

The lateral habenula, a regulator of neuromodulator release, contains a semi-autonomous molecular clock whose significance is unknown. Here, using zebrafish, we investigate the contribution of this clock to change in internal state that is triggered by an aversive stimulus. We focused on the alarm pheromone, Schreckstoff, whose effects vary in a circadian manner. Disruption of habenula clock function, by selective expression of a truncated clock gene (∆CLK), altered the effects of Schreckstoff such that larval responses in the day resembled those at night. Acute responses, including immediate change in swim speed, were unaffected, whereas extended behaviours such as freezing in a novel environment and dark avoidance, were reduced. Circadian behaviours that are under the control of the pineal clock, such as locomotion and sleep, were unchanged. These findings suggest that the habenula clock can act independently to influence the internal state induced by an aversive stimulus.