Light Affects Mood and Learning through Distinct Retina-Brain Pathways.

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.

Multiple Sensory Inputs Are Extensively Integrated to Modulate Nociception in C. elegans.

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. SIGNIFICANCE STATEMENT: Dysfunctional sensory signaling and perception are associated with a number of disease states, including autism spectrum disorders, schizophrenia, and anxiety. We have used the C. elegans model to examine multisensory integration at the interneuron level to better understand the modulation of this complex, multicomponent process. C. elegans responds to a repulsive odorant by first backing up and then either continuing forward or turning and moving away from the odorant. This decision-making process is modulated extensively by the activity state of the two AIB interneurons, with the AIBs integrating an array of synergistic and antagonistic glutamatergic inputs, from sensory neurons responding directly to the odorant to others responding to a host of additional environmental variables to ultimately fine tune aversive behaviors.