Coordinated Prefrontal State Transition Leads Extinction of Reward-Seeking Behaviors.

ABSTRACT

Extinction learning suppresses conditioned reward responses and is thus fundamental to adapt to changing environmental demands and to control excessive reward seeking. The medial prefrontal cortex (mPFC) monitors and controls conditioned reward responses. Abrupt transitions in mPFC activity anticipate changes in conditioned responses to altered contingencies. It remains, however, unknown whether such transitions are driven by the extinction of old behavioral strategies or by the acquisition of new competing ones. Using in vivo multiple single-unit recordings of mPFC in male rats, we studied the relationship between single-unit and population dynamics during extinction learning, using alcohol as a positive reinforcer in an operant conditioning paradigm. To examine the fine temporal relation between neural activity and behavior, we developed a novel behavioral model that allowed us to identify the number, onset, and duration of extinction-learning episodes in the behavior of each animal. We found that single-unit responses to conditioned stimuli changed even under stable experimental conditions and behavior. However, when behavioral responses to task contingencies had to be updated, unit-specific modulations became coordinated across the whole population, pushing the network into a new stable attractor state. Thus, extinction learning is not associated with suppressed mPFC responses to conditioned stimuli, but is anticipated by single-unit coordination into population-wide transitions of the internal state of the animal.SIGNIFICANCE STATEMENT The ability to suppress conditioned behaviors when no longer beneficial is fundamental for the survival of any organism. While pharmacological and optogenetic interventions have shown a critical involvement of the mPFC in the suppression of conditioned responses, the neural dynamics underlying such a process are still largely unknown. Combining novel analysis tools to describe behavior, single-neuron response, and population activity, we found that widespread changes in neuronal firing temporally coordinate across the whole mPFC population in anticipation of behavioral extinction. This coordination leads to a global transition in the internal state of the network, driving extinction of conditioned behavior.