Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction

Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction. To assess potential physiological correlates of these alterations, we compared neural activity in infralimbic and prelimbic cortex of unstressed versus stressed rats during fear conditioning and extinction. After implantation of microwire bundles into infralimbic or prelimbic cortex, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). Rats then underwent fear conditioning and extinction while activity of neurons in infralimbic or prelimbic cortex was recorded. Percent freezing and neural activity were assessed during all phases of training. Chronic stress enhanced freezing during acquisition of conditioned fear, and altered both prelimbic and infralimbic activity during this phase. Stress did not alter initial extinction or conditioned stimulus (CS)-related activity during this phase. However, stress impaired retrieval of extinction assessed 24 h later, and this was accompanied by alterations in neuronal activity in both prelimbic and infralimbic cortex. In prelimbic cortex, unstressed rats showed decreased activity in response to CS presentation, whereas stressed rats showed no change. In infralimbic cortex, neurons in unstressed rats exhibited increased firing in response to the CS, whereas stressed rats showed no increase in infralimbic firing during the tone. Finally, CS-related firing in infralimbic but not prelimbic cortex was correlated with extinction retrieval. Thus, the stress-induced alteration of neuronal activity in infralimbic cortex may be responsible for the stress-induced deficit in retrieval of extinction.