We are interested in how developmental mediators of neuroplasticity play a role in mediating neuroplasticity in the adult brain. Inability of the brain to "adapt," possibly due to aberrant neuroplasticity, may contribute to or exacerbate psychiatric and neurologic disorders such as addiction, depression, post-traumatic stress disorder, or Alzheimer's disease. One mediator that we focus on is adult neurogenesis.

The laboratory's primary focus is on the neuroplasticity that may underlie or accompany psychiatric disorders. For example, long-term exposure to drugs of abuse, such as morphine, heroin, cocaine, and ethanol, can result in cognitive deficits. We have previously shown that neurogenesis is inhibited by chronic exposure to opiates (Eisch et al, 2000). Does the inhibition of adult neurogenesis contribute to the cognitive deficits seen after chronic drug exposure? We have our own self-administration chambers that allow us to ask how a clinically relevant model of addiction, operant i.v. self-administration, alters both neurogenesis and behavior. We are also independently manipulating neurogenesis to see how this influences key aspects of addiction.

We are also interested in the the relationship between mood disorders and adult neurogenesis. Past and future work explores the effects of prescription drugs on adult neurogenesis. For example, we know chronic antidepressant administration increases adult hippocampal neurogenesis. Could alterations in adult hippocampal neurogenesis play a role in depression and in the response to antidepressants? How does periadolescent administration of methylphenidate, a drug commonly used in children to treat ADHD, affect adult hippocampal neurogenesis? Do new neurons regulate the behavioral response of an animal to a stressful situation?

Other examples of our interest in adult neurogenesis and pyschiatry is our exploration of the birth of new neurons in a mouse model of Alzheimer's disease, the role that growth factors play in development of a depressive-like phenotype, the potential involvement of adult-generated neurons in a mouse model of severe social stress, and the impact of irradiation (both X-ray and cosmic) or voluntary exercise on adult neurogenesis.

Since our ultimate goal is to understand not only if and how new neurons are involved in psychiatric disorders but also "What makes stem cells in the brain tick?", our current and future studies rely on a variety of in vivo and in vitro approaches. These including immunohistochemistry and cytochemistry along with confocal and two-photon microscopy; transgenic and viral-mediated manipulation of stem and progenitor cells; transgenic, chemical, and irradiation-induced ablation of newly born cells; stereotaxic labeling and lesioning of discrete cells and brain regions; behavioral and metabolic assessment (addiction, depression, anxiety, satiety, etc.); and fundamental in vitro approaches like fluorescent-activated cell sorting followed by the neurosphere assay.