Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here, we reveal that the direct effects of light on learning and mood utilize distinct ipRGC output streams. ipRGCs that project to the suprachiasmatic nucleus (SCN) mediate the effects of light on learning, independently of the SCN's pacemaker function. Mood regulation by light, on the other hand, requires an SCN-independent pathway linking ipRGCs to a previously unrecognized thalamic region, termed perihabenular nucleus (PHb). The PHb is integrated in a distinctive circuitry with mood-regulating centers and is both necessary and sufficient for driving the effects of light on affective behavior. Together, these results provide new insights into the neural basis required for light to influence mood and learning.

Sensory inputs are integrated extensively before decision making, with altered multisensory integration being associated with disorders such as autism. We demonstrate that the two C. elegans AIB interneurons function as a biphasic switch, integrating antagonistic, tonic, and acute inputs from three distinct pairs of sensory neurons to modulate nociception. Off food, animals reverse away from a noxious stimulus. In contrast, on food or serotonin, AIB signaling is inhibited and, although animals initiate an aversive response more rapidly, they continue forward after the initial backward locomotion is complete. That is, animals continue to move forward and feed even when presented with a noxious repellant, with AIB inhibition decreasing the repellant concentration evoking a maximal response. These studies demonstrate that the AIBs serve as an integrating hub, receiving inputs from different sensory neurons to modulate locomotory decision making differentially, and highlight the utility of this model to analyze the complexities of multisensory integration.