Model Reference Current Injection: A High-Speed Next-Generation Dynamic Clamp

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

Abstract Butera The "dynamic-clamp" is an electrophysiological technique developed in the past decade that utilizes real-time voltage-measurements from electrically excitable cells, such as neurons and cardiac myocytes. These measurements are used by a computational model running in real-time to compute artificial ionic currents that are injected into (the same or another) excitable cells. Applications of this technique include augmenting the intrinsic electrical properties of a single cell or using the computer to connect isolated cells to create an artificial network consisting of real neurons and computed synapses. This approach has seen growing use in the neuroscience and cardiac electrophysiology communities. However, the technique is nontrivial to implement and off-the-shelf (turnkey) approaches have not kept pace with rapidly changing computing technologies. Furthermore, although many laboratories have used this technique, little research has been done to evaulate its accuracy and validity. The objective of this application is to develop a next-generation system that implements the dynamic-clamp tecnique and utilizes currently avaiable computing technologies. This technique will be low-cost, using computers and electrophysiolgical hardware available in most neurophysiological laboratories; fully-featured, allowing for very high speeds (with a goal of 100 kHz), arbitrary model specifications, and real-time data logging on the control computer; and open-source, meaning that the software and operating system upon which it is based are freely distributable and freely modifiable to suit a laboratory's specific needs. Conventional desktop operating systems are unsuitable for real-time performance in the 10's of kHz range, thus this project will use Real-Time Linux, a derivative of the Linux operating system modified for performing real-time tasks, to achieve these goals. The specific objectives of this project are to develop a core real-time control computational engine based on Real-Time Linux, develop a user interface and mechanism for arbitrary model specification, and perform rigorous testing of the accuracy and validity of the technique. This technology will impact the neuroscience and electrophysiology fields of research in several ways. First, it will make the technique available to more researchers, with a greater array of features available. Second, the increased speed of this approach will allow new experiments to be performed using the dynamic clamp, such as those involving membrane processes with submillisecond time-constants, such as sodium currents in cardiac myocytes and synaptic currents from fast AMPA synapses.