From RNA to reward: dissecting habenular circuit activity during motivated behavior.
The nervous system must continuously process sensory stimuli, evaluate outcomes, and apply learned rules to future behavior. To accomplish these diverse tasks, neural circuits are specialized at the systems, cellular, and molecular levels. At the systems level, the habenula links emotionally salient information from the limbic forebrain to neuromodulatory centers in the midbrain, and has been implicated in a variety of different behaviors and neuropsychiatric disorders, including addiction and depression. The habenula also displays a striking degree of molecular heterogeneity in neurotransmitters, neuromodulators, ion channels, and synaptic adhesion molecules, suggesting a functional specialization of habenular neurons. However, information linking molecularly-defined cell types to specific aspects of behavior is limited. Using viral projection mapping and calcium monitoring of multiple cell types during reward-guided behavior, we find that habenular subpopulations exhibit cell-type specific axonal trajectories and activity dynamics. Separate neuronal populations encode either reward-predictive sensory cues or behavioral outcome, and both adapt their activity to changing reward contingencies. These data suggest that medial habenula neurons process multiple aspects of reward-guided behavior. Habenular neurons are well positioned to relay limbic information to midbrain dopaminergic and serotonergic nuclei, and could serve as a mechanism to modulate motivated behavior in di