1 Center for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montreal, Québec, Canada.
2 Sussex Neuroscience, School of Psychology, University of Sussex, Falmer, United Kingdom.
3 Behavioral Neuroscience Branch Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland.
4 Department of Psychology, Brooklyn College of the City University of New York, Brooklyn, New York.
5 Center for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montreal, Québec, Canada. Electronic address: mihaela.iordanova@concordia.ca.

Background: Adaptive behavior depends on the delicate and dynamic balance between acquisition and extinction memories. Disruption of this balance, particularly when the extinction of memory loses control over behavior, is the root of treatment failure of maladaptive behaviors such as substance abuse or anxiety disorders. Understanding this balance requires a better understanding of the underlying neurobiology and its contribution to behavioral regulation.

Methods: We microinjected Daun02 in Fos-lacZ transgenic rats following a single extinction training episode to delete extinction-recruited neuronal ensembles in the basolateral amygdala (BLA) and central nucleus of the amygdala (CN) and examined their contribution to behavior in an appetitive Pavlovian task. In addition, we used immunohistochemistry and neuronal staining methods to identify the molecular markers of activated neurons in the BLA and CN during extinction learning or retrieval.

Results: CN neurons were preferentially engaged following extinction, and deletion of these extinction-activated ensembles in the CN but not the BLA impaired the retrieval of extinction despite additional extinction training and promoted greater levels of behavioral restoration in spontaneous recovery and reinstatement. Disrupting extinction processing in the CN in turn increased activity in the BLA. Our results also show a specific role for CN PKCd+ neurons in behavioral inhibition but not during initial extinction learning.

Conclusions: We showed that the initial extinction-recruited CN ensemble is critical to the acquisition-extinction balance and that greater behavioral restoration does not mean weaker extinction contribution. These findings provide a novel avenue for thinking about the neural mechanisms of extinction and for developing treatments for cue-triggered appetitive behaviors.