Encoding and context-dependent control of reward consumption within the central nucleus of the amygdala.

Dysregulation of the central amygdala is thought to underlie aberrant choice in alcohol use disorder, but the role of central amygdala neural activity during reward choice and consumption is unclear. We recorded central amygdala neurons in male rats as they consumed alcohol or sucrose. We observed activity changes at the time of reward approach, as well as lick-entrained activity during ongoing consumption of both rewards. In choice scenarios where rats could drink sucrose, alcohol, or quinine-adulterated alcohol with or without central amygdala optogenetic stimulation, rats drank more of stimulation-paired options when the two bottles contained identical options. Given a choice among different options, central amygdala stimulation usually enhanced consumption of stimulation-paired rewards. However, optogenetic stimulation during consumption of the less-preferred option, alcohol, was unable to enhance alcohol intake while sucrose was available. These findings indicate that the central amygdala contributes to refining motivated pursuit toward the preferred available option.

Encoding and context-dependent control of reward consumption within the central nucleus of the amygdala.

The ability to evaluate and select a preferred option among a variety of available offers is an essential aspect of goal-directed behavior. Dysregulation of this valuation process is characteristic of alcohol use disorder, with the central amygdala being implicated in persistent alcohol pursuit. However, the mechanism by which the central amygdala encodes and promotes the motivation to seek and consume alcohol remains unclear. We recorded single-unit activity in male Long-Evans rats as they consumed 10% ethanol or 14.2% sucrose. We observed significant activity at the time of approach to alcohol or sucrose, as well as lick-entrained activity during the ongoing consumption of both alcohol and sucrose. We then evaluated the ability of central amygdala optogenetic manipulation time-locked to consumption to alter ongoing intake of alcohol or sucrose, a preferred non-drug reward. In closed two-choice scenarios where rats could drink only sucrose, alcohol, or quinine-adulterated alcohol with or without central amygdala stimulation, rats drank more of stimulation-paired options. Microstructural analysis of licking patterns suggests these effects were mediated by changes in motivation, not palatability. Given a choice among different options, central amygdala stimulation enhanced consumption if the stimulation was associated with the preferred reward while closed-loop inhibition only decreased consumption if the options were equally valued. However, optogenetic stimulation during consumption of the less-preferred option, alcohol, was unable to enhance overall alcohol intake while sucrose was available. Collectively, these findings indicate that the central amygdala processes the motivational value of available offers to promote pursuit of the most preferred available option.

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system.

Adaptive behavior in a dynamic environment often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical test to theories of dopamine's function in learning, motivation, and motor control. Yet how dopamine neurons are involved in the revaluation of cues when the world changes to alter our behavior remains unclear. Here we make use of pharmacology, in vivo electrophysiology, fiber photometry, and optogenetics to resolve the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward-seeking. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by sucrose reward by exploiting the prior, non-overlapping presentation of a separate discrete cue - an occasion setter. Only when the occasion setter's presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery. As a result, in this task we were able to dissociate the average value of the conditioned stimulus from its immediate expected value on a trial-to-trial basis. Both the activity of ventral tegmental area dopamine neurons and dopamine signaling in the nucleus accumbens were essential for rats to successfully update behavioral responding in response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward. Downstream of dopamine release, we found that single neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together these results reveal a novel mechanism within the mesolimbic dopamine system for the rapid revaluation of motivation.