This K0l (MRSDA) application outlines training and supervised research in both experimental and theoretical approaches for understanding modulatory influences on cortical network behavior. The core of this proposal involves investigation of a central hypothesis that intrinsic ensemble dynamics of cortical networks will change in response to perturbations of the system by modulatory neurotransmitters. The proposal consists of specific aims for understanding the dynamics of isolated cortical networks to be accomplished within the award as well as the development of an experimental and theoretical framework on which to base extended career goals. ? ? Theory and experiment are integrated throughout the proposed work, however the initial phase of the award is focused on learning and applying imaging and electro-physiology techniques to map network behavior in cortical slices and understand the influence of modulatory neurotransmitters. The second period of the proposed work is more heavily theoretical, and also involves a didactic period as suggested in KO1 guideline. The final phase is more oriented towards career development, with translation towards fully independent funding and research as described in the NIMH KO1 guidelines. The candidate's long-term goals are to explore the effects of other diffuse influences on cortical function such as metabolism, stress and disease, and to move studies like these towards in-vivo preparations. ? ? The candidate is well suited to leverage the proposed training towards the investigation of the problems outlined in short and long-term goals. The candidate has both a diverse experimental background, most recently focused on the cell biology of neurodegeneration, and theoretical experience with detailed biophysical models at the compartment level as well as at the level of large-scale spatiotemporal simulations. The advanced imaging techniques, the work in mammals at a systems level and the theoretical techniques outlined in the proposal are new to the candidate. Both experimental and theoretical mentors are leaders in their respective fields and are ideal for the proposed training. NYU and the Courant Institute offer a rich environment for theory and experimental interactions, and the experimental mentor offers a superbly equipped laboratory for the proposed experimental work at Columbia. Finally, the candidate proposes an advisory committee, as suggested in KO1 guidelines, for consultation on various aspects of the proposed work.
