NEURAL MECHANISMS OF GOAL DIRECTED BEHAVIOR

Abstract

Organisms are often motivated by goals which are spatially and temporally distant. Animals travel large distances, risking their lives in search of food, water, or a mate. How does the animal remain motivated and focused on the goal? How does the animal change its behavior adaptively in varying environmental conditions? Here, we reveal a role for two major neuromodulators in different behavioral contexts – dopamine when animals seek distant rewards and serotonin when animals behave adaptively in environments with different valence. We measured population calcium activity of dopamine neurons in ventral tegmental area as mice learned a variety of reward seeking tasks. When mice navigated through space toward a goal, dopamine activity progressively increased or ramped upand peaked at the goal. This ramping dopamine activity was sensitive to reward magnitude and emerged quickly within a few trials after the first reward exposure in naïve animals. Physical action was not necessary to produce dopamine ramps; dynamic sensory feedback of progress to reward alone can produce dopamine ramps. However, dopamine ramps driven by sensory feedback were short lived. When the animal was required to use an internal model of distance to reward, in the absence of sensory feedback, the dopamine ramps were robust and did not fade over training. Collectively, these results suggest that dopamine ramps reflect an internal model of goal proximity information. Next, we measured population activity of serotonin neurons in the dorsal raphe nucleus when animals were in a moderate threat or a high threat environment. We found that the serotonin neural activity decreased during movement initiation in a moderate threat environment but increased during movement initiation in a high threat environment. We then measured calcium activity of individual serotonin neurons when animals were exposed to environments at differentthreat levels. We found that individual serotonin neurons switched their movement-related neural activity when mice transitioned from moderate threat to high threat environments, signifying routing of environmental valence information to individual serotonin neurons. Together, this research provides insights into the neural mechanisms underlying environmental valence-dependent adaptive behaviors and sustained goal directed behaviors.