Stress-induced prefrontal reorganization and executive dysfunction in rodents

Abstract

The prefrontal cortex (PFC) mediates a range of higher order 'executive functions' that subserve the selection and processing of information in such a way that behavior can be planned, controlled and directed according to shifting environmental demands. Impairment of executive functions typifies many forms of psychopathology, including schizophrenia, mood and anxiety disorders and addiction, that are often associated with a history of trauma and stress. Recent research in animal models demonstrates that exposure to even brief periods of intense stress is sufficient to cause significant structural remodeling of the principle projection neurons within the rodent PFC. In parallel, there is growing evidence that stress-induced alterations in PFC neuronal morphology are associated with deficits in rodent executive functions such as working memory, attentional set-shifting and cognitive flexibility, as well as emotional dysregulation in the form of impaired fear extinction. Although the molecular basis of stress-induced changes in PFC morphology and function are only now being elucidated, an understanding of these mechanisms could provide important insight into the pathophysiology of executive dysfunction in neuropsychiatric disease and foster improved strategies for treatment.

Fig. 1

Schematic diagram of coronal sections through PFC, with major subdivisions of rodent PFC orchestrating stress responses and mediating executive function identified. Coordinates given are relative to Bregma in mouse brain. AC = anterior cingulate; PL = prelimbic; IL = infralimbic; MO = medial orbitofrontal; VO = ventral orbitofrontal; LO = Lateral Orbitofrontal; DLO = dorsolateral orbitofrontal (adapted from Paxinos and Franklin, 2001).