Real-time methods in neural electrophysiology to improve efficacy of dynamic clamp

In the central nervous system, most of the processes ranging from ion channels to neuronal networks occur in a closed loop, where the input to the system depends on its output. In contrast, most experimental preparations and protocols operate autonomously in an open loop and do not depend on the output of the system. Real-time software technology can be an essential tool for understanding the dynamics of many biological processes by providing the ability to precisely control the spatiotemporal aspects of a stimulus and to build activity-dependent stimulus-response closed loops. So far, application of this technology in biological experiments has been limited primarily to the dynamic clamp, an increasingly popular electrophysiology technique for introducing artificial conductances into living cells. Since the dynamic clamp combines mathematical modeling with electrophysiology experiments, it inherits the limitations of both, as well as issues concerning accuracy and stability that are determined by the chosen software and hardware. In addition, most dynamic clamp systems to date are designed for specific experimental paradigms and are not easily extensible to general real-time protocols and analyses. The long-term goal of this research is to develop a suite of real-time tools to evaluate the performance, improve the efficacy, and extend the capabilities of the dynamic clamp technique and real-time neural electrophysiology. We demonstrate a combined dynamic clamp and modeling approach for studying synaptic integration, a software platform for implementing flexible real-time closed-loop protocols, and the potential and limitations of Kalman filter-based techniques for online state and parameter estimation of neuron models.Ph.D