This seminar has unfortunately been cancelled.
Maintaining average activity level within a set-point range constitutes a fundamental property of central neural circuits. Accumulated evidence suggests that mean firing rate (MFR), reflecting an average level of spontaneous spiking activity over extended timescales, represents a physiological variable regulated by homeostatic systems in central neural circuits. However, some central questions have remained open. What are the mechanisms that establish the specific values of MFR set-points? Are MFR set-points fixed (predetermined) or adjustable in central neural circuits? If they are adjustable, do separate mechanisms control negative feedback responses and MFR set-point value? And finally, whether re-adjustment of dysregulated firing set-points may provide a new conceptual way to treat brain disorders associated with aberrant network activity? I will present our new approach, integrating genome-scale metabolic modeling and experimental study of neuronal homeostasis, to predict homeostatic regulators in specific neural circuits. Next, I will show our new results on the role of mitochondrial signaling in the regulation of activity set-points in hippocampal circuits ex vivo and in vivo. Finally, I will provide the evidence for a new potential strategy to suppress seizures by lowering firing set-points.