The habenula clock regulates response to a stressor

The lateral habenula, a regulator of neuromodulators that is activated by aversive stimuli, contains a molecular clock whose significance is unknown. Here, using zebrafish, we test the hypothesis that the habenula clock affects the switch in internal state that is triggered by an aversive stimulus. Consistent with the expression of clock genes, habenula neural activity varies in a circadian manner. Disruption of clock function, by expression of a truncated clock gene specifically in the habenula, did not affect acute responses to the alarm pheromone Schreckstoff. However, behaviours elicited by transient exposure to Schreckstoff, namely freezing in a novel environment and dark avoidance, were reduced. Behaviours that are regulated by the pineal clock and not triggered by stressors were unaffected. These findings establish that the habenula clock independently influences the stress response induced by an aversive stimulus, indicating that this clock underlies circadian variation in response to a stressor.