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The recruitment of a neuronal ensemble in the CN during the first extinction episode has persistent effects on extinction expression

      Abstract

      Background

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

      Methods

      We microinjected Daun02 in Fos-lacZ transgenic rats following a single extinction training to delete extinction-recruited neuronal ensembles in the basolateral (BLA) and central (CN) nuclei of the amygdala and examine their contribution to behaviour 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 this extinction-activated ensembles in CN but not BLA impaired the retrieval of extinction even despite additional extinction training, and promoted greater levels of behavioural 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 PKCδ+ neurons in behavioural inhibition but not during initial extinction learning.

      Conclusion

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

      Key words

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