"Neuronal circuits of fear conditioning and extinction learning."
Le 26 mai 2014
Experience-dependent changes in behavior are mediated by long-term functional modifications in brain circuits. To study the underlying mechanisms, my laboratory is using classical auditory fear conditioning, a simple and robust form of associative learning. In classical fear conditioning, the subject is exposed to a noxious unconditioned stimulus (US), such as a foot-shock, in conjunction with a neutral conditioned stimulus (CS), such as a tone. As a result of the training, the tone acquires aversive properties and when subsequently presented alone, will elicit fear responses, including an immobilization reaction called freezing.
Subsequently, conditioned fear can be suppressed when the conditioned stimulus is repeatedly presented alone, a phenomenon called fear extinction. The canonical view of the neuronal circuits involved in conditioned fear behavior and extinction learning suggest that fear memories are formed and stored within the basolateral amygdala via activity-dependent plasticity mechanisms. In this model the central amygdala is exclusively involved in the expression of conditioned fear behavior notably through projections to brainstem structures. Moreover, a large body of evidence also indicates that the medial prefrontal cortex plays a key role in the control of fear behavior and that distinct prefrontal sub-regions differentially regulate the expression and inhibition of fear responses during extinction learning.
The research activity presented here has contributed to the recent refinement of this classical model notably by showing that (i) in addition to the basolateral amygdala, both the auditory cortex and the central amygdala are instrumental neuronal elements in the formation of fear memories, (ii) extinction learning is encoded within the basal amygdala by a particular class of neurons labelled extinction neurons, (iii) in juveniles, extinction erases the original fear memory whereas in adults, it temporarily inhibits fear responses thereby providing a description of the developmental regulation of fear extinction neuronal mechanisms and (iv) dedicated prefrontal circuits involving PV-expressing interneurons disinhibit and synchronize prefrontal output neurons projecting to the amygdala to regulate fear expression.
Taken together, these findings revealed a complex interplay between cortical and subcortical structures in the regulation of fear behavior and suggest the involvement of specific neuronal populations. Ultimately, understanding these mechanisms is fundamental to develop new therapeutic strategies for pathological conditions such as anxiety disorders.
- Thérèse Jay
DR INSERM, Paris – Présidente
- René Garcia
PR Nice – Rapporteur
- Sidney Wiener
DR CNRS, Paris – Rapporteur
- François Georges
CR1 CNRS, Bordeaux – Rapporteur
- Jérôme Baufreton
CR1 CNRS, Bordeaux – Examinateur
Dernière mise à jour le 20.05.2014