Corticostriatal control of extinction in appetitive Pavlovian conditioning

Animals use environmental cues to guide their behaviour to obtain desirable outcomes and avoid aversive ones. Through extinction, animals can learn to suppress learned behaviours when the expected appetitive or aversive outcome is omitted. The infralimbic cortex (IL) and its efferent projections to the nucleus accumbens shell (NAcS) and the basolateral amygdala (BLA) are thought to be critical for extinction and suppressing responding to cues that predict aversive outcomes and responding for drugs of abuse. However, fewer research has investigated whether the IL and its neural projections are important for extinction of responding to cues that predict more naturalistic appetitive outcomes. The present thesis examined the effects of augmenting activity in the IL, the IL-to-NAcS projection, and the IL-to-BLA projection on extinction of conditioned approach to a sucrose cue. In two experimental chapters (Chapters 3 and 4) we used a renewal task, to test whether optogenetic stimulation of the IL, IL-to-NAcS, and IL-to-BLA would suppress the return of responding after extinction. Briefly, in the renewal task, rats first received Pavlovian conditioning in a specific context (Context A) to associate an auditory conditioned stimulus (CS) with the delivery of a sucrose unconditioned stimulus (US). Next, rats received extinction in a different context (Context B) by presenting the CS but omitting the expected US, leading to a reduction in conditioned responding. After extinction, renewal of responding to the CS was triggered by presenting the CS alone in the original Pavlovian conditioning context (Context A). We found that optogenetic stimulation of the IL and IL-to-NAcS projection but not the IL-to-BLA projection during the CS attenuated the renewal of appetitive Pavlovian conditioned responding. In the last chapter (Chapter 5), we explored potential mechanisms by which stimulation of the IL-to-NAcS projection suppresses appetitive Pavlovian conditioned responding. First, we tested whether prior extinction training was necessary for IL-to-NAcS stimulation to suppress conditioned responding. Second, we tested whether stimulation during Pavlovian conditioning would lead to general suppression of responding. We found that IL-to-NAcS stimulation during the CS suppressed conditioned responding regardless of prior extinction training. Further, IL-to-NAcS stimulation during Pavlovian conditioning did not appear to indiscriminately suppress responding, but altered the expression of conditioned responding to the CS. In conclusion, the findings of the present thesis expand the role of the IL and IL-to-NAcS projection in extinction to appetitive Pavlovian cues. Further, we provide novel evidence that suppression of appetitive Pavlovian responding following IL-to-NAcS stimulation may not be dependent on an extinction process. Nevertheless, the IL-to-NAcS projection plays an important role in controlling conditioned responding to appetitive cues. These findings further our knowledge of how corticostriatal circuits contribute to adaptive behaviour which may be useful for understanding psychological disorders involving inhibition of learned behaviours