Stimulus generalization and return of fear in C57BL/6J mice

Return of fear following successful exposure therapy is a common problem. More insight into the characteristics of extinction learning is crucial in enhancing the efficiency of therapeutic interventions. In particular, understanding the mechanisms that underlie the generalization of extinction learning to other discrete stimuli is indispensable. Presently, little is known about the molecular and genetic mechanisms underlying this phenomenon. In this study, we attempt to develop a new conditioning protocol to study return of fear, caused by a stimulus change after extinction, in the most commonly used mouse strain of behavioral genetics, C57BL/6J. Perceptual changes to an auditory fear conditioned stimulus led to return of fear after initially successful fear-reduction, relative to appropriate control treatment. We argue that this protocol will be a useful tool to unravel the neurobiological underpinnings that regulate generalization of extinction and return of fear. Key questions for future research include the identification of crucial brain structures, neurotransmitters and signaling pathways that underly this behavioral phenomenon. Arguably, such research will open up new perspectives for neurobiological therapy augmentation.