Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023)

The capacity to inhibit actions and reactions when an anticipated environmental stimulus no longer occurs is critical for flexible, adaptive behaviour. The ensuing decrement in conditioned responding, referred to as extinction, has been extensively researched using aversive Pavlovian conditioning procedures in which a conditional stimulus (CS) is paired with a noxious unconditional stimulus (US), and then the US is withheld to induce extinction. Results suggest that extinction produces a new inhibitory memory that competes with the original learning for control over responding. Specifically, a new CS-no US memory is formed during extinction that competes with the original CS-US memory to suppress responding. My program of research seeks to understand how the brain regulates the formation and retention of extinction memory.

This area of research is shaped by the influential hypothesis that distinct cortical projections originating in the infralimbic subregion of the medial prefrontal cortex and terminating in either the amygdala or nucleus accumbens shell mediate the extinction of responding associated with aversive or appetitive (positive) stimuli, respectively. However, a consideration that has been overlooked in the development of this hypothesis is that research using aversive stimuli is conducted using Pavlovian learning models, whereas research using appetitive stimuli has almost exclusively been conducted using instrumental conditioning procedures. In the latter, operant responding is reinforced by an appetitive stimulus, which is subsequently withheld to induce extinction. Given that the original memory is acquired via different learning processes, we propose that it may be the learning process (Pavlovian or instrumental) and not the nature of stimulus (aversive or appetitive) that recruits distinct projections from the infralimbic cortex during extinction.

We will use a multidisciplinary approach to test this novel hypothesis in rats. Using immunohistochemistry we will examine the activation of infralimbic projections to the nucleus accumbens shell or basolateral nucleus of the amygdala by extinction in appetitive Pavlovian and instrumental conditioning procedures. Using innovative in vivo optogenetic and chemogenetic strategies we will dissect the roles of these two projections in the extinction of appetitive instrumental conditioning, and appetitive and aversive Pavlovian conditioning. Results from this timely proposal will form the basis for new research aimed at identifying the molecular, neurochemical and genetic processes within well-defined neural circuits that mediate the extinction of appetitive conditioned responding. Overall, this line of research will expand our understanding of how the brain regulates the inhibition of actions and reactions when anticipated environmental stimuli fail to occur.