MRSDA Candidate: The applicant describes a plan to broaden his research experience and skills in sophisticated imaging approaches for cellular neuroscience. A mechanism of structural plasticity on dendrites of CA1 hippocampal pyramidal neurons will be investigated drawing on techniques in serial electron microscopy and immunogold labeling, and training in multiphoton laser scanning microscopy, one of the most advanced techniques for live tissue imaging. The candidate's long-term goal is to become an independent investigator in an academic setting. Environment: The MRSDA sponsor is one of the foremost researchers studying synaptic ultrastructure. The investigator will interact with developmental, cellular, molecular, and systems neurobiologists as well as neuroethologists in a diverse Department of Biology and neuroscientists in other Departments. Two faculty collaborators with expertise in immunogold labeling and optical physics will participate in the MRSDA program. The sponsor's laboratory is outstanding, possessing all of the physical and instrumental resources needed for this MRSDA program and comprised of research professionals, postdoctoral fellows, and technical staff. Research: Most excitatory synapses in the adult brain occur on dendritic spines and changes in spine number or structure and composition can affect communication between neurons. It was thought that spine number would increase to meet the demand of enhanced synaptic activity and vice versa. We have shown on the mature hippocampal neurons that spine number dramatically increases when synaptic activity is reduced or blocked. In contrast, developing neurons appear to require activation to initiate spine formation. The MRSDA specific aims are: 1) Determine under what conditions of neuronal activity dendritic spines form on immature hippocampal neurons. 2) Establish the ultrastructural locations of synapses under conditions of spine formation on immature hippocampal neurons. 3) Determine how rapidly new spines can form on mature hippocampal neurons when synaptic activity is blocked. 4) Compare the composition and detailed structure of newly formed versus previously stable dendritic spines on mature hippocampal neurons. The results will have important implications for understanding how new spines might be generated when overall neuronal activity is low and could be lost during excessive activation such as with epileptic seizures.
