Preclinical studies of stress, extinction, and prefrontal cortex: intriguing leads and pressing questions.

BACKGROUND: Stress is associated with cognitive and emotional dysfunction, and increases risk for a variety of psychological disorders, including depression and posttraumatic stress disorder. Prefrontal cortex is critical for executive function and emotion regulation, is a target for stress hormones, and is implicated in many stress-influenced psychological disorders. Extinction of conditioned fear provides an excellent model system for examining how stress-induced changes in corticolimbic structure and function are related to stress-induced changes in neural function and behavior, as the neural circuitry underlying this behavior is well characterized.

OBJECTIVES: This review examines how acute and chronic stress influences extinction and describes how stress alters the structure and function of the medial prefrontal cortex, a potential neural substrate for these effects. In addition, we identify important unanswered questions about how stress-induced change in prefrontal cortex may mediate extinction deficits and avenues for future research.

KEY FINDINGS: A substantial body of work demonstrates deficits in extinction after either acute or chronic stress. A separate and substantial literature demonstrates stress-induced neuronal remodeling in medial prefrontal cortex, along with several key neurohormonal contributors to this remodeling, and there is substantial overlap in prefrontal mechanisms underlying extinction and the mechanisms implicated in stress-induced dysfunction of-and neuronal remodeling in-medial prefrontal cortex. However, data directly examining the contribution of changes in prefrontal structure and function to stress-induced extinction deficits is currently lacking.

CONCLUSIONS: Understanding how stress influences extinction and its neural substrates as well as individual differences in this effect will elucidate potential avenues for novel interventions for stress-sensitive disorders characterized by deficits in extinction.