Sex differences and chronic stress effects on the neural circuitry underlying fear conditioning and extinction

- Expression and rates of stress-dependent psychopathology are sex-dependent.
- Remodeling of fear circuits may contribute to sex differences in psychopathology.
- Sex and stress alter medial prefrontal cortex dendritic morphology.
- There are sex-dependent stress effects on fear conditioning and extinction.
- Dendritic remodeling may underlie sex and stress effects on emotional learning.

There are sex differences in the rates of many stress-sensitive psychological disorders such as posttraumatic stress disorder (PTSD). As medial prefrontal cortex and amygdala are implicated in many of these disorders, understanding differential stress effects in these regions may shed light on the mechanisms underlying sex-dependent expression of disorders like depression and anxiety. Prefrontal cortex and amygdala are key regions in the neural circuitry underlying fear conditioning and extinction, which thus has emerged as a useful model of stress influences on the neural circuitry underlying regulation of emotional behavior. This review outlines the current literature on sex differences and stress effects on dendritic morphology within medial prefrontal cortex and basolateral amygdala. Such structural differences and/or alterations can have important effects on fear conditioning and extinction, behaviors that are mediated by the basolateral amygdala and prefrontal cortex, respectively. Given the importance of extinction-based exposure therapy as a treatment for anxiety disorders such as PTSD, understanding the neural mechanisms by which stress differentially influences fear learning and extinction in males and females is an important goal for developing sex-appropriate interventions for stress-related disorders.