Prefrontal mechanism of resilience after adolescent chronic stress: Implications for dysregulation of fear responses in a model of posttraumatic stress disorder

COTELLA, EVELIN M.

Virtual

Congreso; Reunión anual Sociedad Argentina de Neurociencia; 2020

Developmental stress is usually considered negative, although it is thought that mild to moderate stress during this period can sometimes promote adaptive responses, contributing to adult resilience. We first characterized the effects of chronic variable stress in adolescence (adol CVS) on behaviors related to corticolimbic functionality, to assess possible adult vulnerability and resilience to stress. Sprague Dawley rats were subjected to variable chronic stress in adolescence (adol CVS, 2 weeks, PND45). Adol CVS attenuated the impact of single prolonged stress (SPS), a robust model of PTSD on extinction and reinstatement in a fear conditioning paradigm. The analysis of Fos immunoreactivity pointed to the infralimbic cortex (IL) as a strong candidate for the mechanism behind the effect. We then studied the effect inhibition of IL activity during the experience of SPS by chemogenetics. This intervention enhanced the outcomes in a fear conditioning paradigm, pointing also to a possible involvement of the IL in mechanisms behind risk to PTSD after traumatic experiences. By electrophysiology, we observed that adol CVS is capable of preventing the reduction in excitability of the IL evoked by SPS. Our results indicated involvement of the IL in mediating effects related to resilience after adolescent stress and added new insights into the possible mechanisms behind developmentally driven interindividual differences in the vulnerability to disorders such as PTSD.