Stress has been hypothesized to play a major role in several disorders, and the neurotransmitter systems and brain structures that are altered by stress have been implicated in a variety of psychological disorders. Thus, assessment of the effects of stress on these neurotransmitter systems and structures may have important implications for the causes and prevention of these disorders. Prefrontal cortex is a target for hormones involved in the stress response and has been implicated in disorders such as schizophrenia and depression that are exacerbated or precipitated by stress. Thus, understanding the effects of stress on prefrontal cortex is critical for understanding the influence of stress on psychopathology. My lab is examining the effects of chronic stress and stress hormones on behaviors mediated by prefrontal cortex, as well as the changes in neural pharmacology and morphology that underlie these effects. We have demonstrated that both chronic stress and exposure to the stress hormone corticosterone reorganize dendrites of neurons in prefrontal cortex. We are now beginning to more fully characterize these effects, assess their functional significance, and elucidate mechanisms underlying them.

Neural plasticity underlies a variety of processes, including development, learning and memory, and recovery from injury. Plasticity persists throughout the lifespan, but evidence suggests that this plasticity may be reduced in aging. For instance, the behavioral effects of moderate head injuries are more pronounced in aged patients. Similarly, aging prolongs the behavioral consequences of traumatic brain injury in rats, and aged rats are differentially vulnerable to the effects of loss of input to the hippocampus. These differential responses to injury or lesion suggest that plasticity is altered in the aged, which has important consequences for both successful aging and treatment of neural disorders in the elderly. I have used lesions of the nucleus basalis in rats to assess neurochemical and morphological plasticity in frontal cortex. This work has demonstrated altered plasticity in frontal cortex of aging rats—lesions produce greater dendritic atrophy and differential changes in the glutamatergic system in aged rats. A current focus of the lab is to assess the mechanisms that underlie age-related changes in plasticity of frontal cortex and to determine how these changes influence behaviors mediated by frontal cortex. In answering these questions, I hope to contribute to our understanding of the basic mechanisms of neural changes in aging, as well as the causes and treatment of age-related dementias.