DESCRIPTION: This is a request for an NIMH Senior Scientist Award (SSA). At the age of 52, with over 30 years of research experience, I request freedom from non-research duties in order to focus on an expanded research program and take advantage of a unique and timely opportunity to learn MRI in humans. The major aim of my present research program is to examine the basic cellular and pharmacological mechanism of serotonin-mediated neuroplasticity in the rodent brain and spinal cord. The research proposed for the next five years focuses my efforts on expanding my basic research objectives and extending them to include clinical research. In basic research, I will study the serotonin involvement with neurogenesis and apoptosis. My current hypothesis is that 5-HT1A receptor protein levels and expression are inversely correlated with neuronal maturation. Dr. Jacobs finds neurogenesis is stimulated by 5-HT1A receptor agonists. Dr. Banerjee reports 5-HT1A agonists activate MAP-kinase, which inhibits caspase-3 activity and apoptosis, in a neuronal cell line. I am positioned to move into these areas and expand on my current NIMH supported research that linked the 5-HT1A receptor to neuroplasticity and depression. I will expand my hypothesis to include events occurring during neurogenesis and apoptosis. The second major career plan involves acquiring the background and experience to perform and analyse MRI in the human brain. Dr. Mony DeLeon uses MRI to detect morphological changes in entorhinal cortex, amygdala and hippocampus at NYU Medical Center. My long-term aims are to use imaging techniques for longitudinal study of a psychiatric patient population where neuroplastic events are suspected. Therapeutic strategies using 5-HT drugs would enable direct testing of the clinical relevance of my basic research findings. Professional growth plans involve (a) supplemental training in human imaging technology; (b) explore the role of the 5-HT1A receptor in neurogenesis and apoptosis and (c) meet with national and international experts in the field of neuroplasticity as part of further development of therapeutic strategies for using pharmacology to reverse neuromorphological changes occurring in mental disorders.