This SGER proposal is to complete development of the "Dynamic Clamp" which is a software tool for on-line electrophysiological analysis of neurons and neuronal circuits. Present microelectrode techniques make it possible to record membrane potential changes in response to intrinsic neuronal activity and to injected current, and to record local membrane currents under voltage clamp. The dynamic clamp provides a significant advance for recording and experimental manipulation of neuronal and network responses by making it possible to simulate evoked and voltage-dependent conductance changes in a neuron in real time during an experiment. This makes it possible to simulate an electrical or chemical synaptic connection between two neurons, to simulate the effect of a neuromodulator substance, and to simulate the effect of voltage- dependent membrane currents. Currents or synapses can be added or subtracted or changed in a neuron, and the effect of these manipulations can be directly assessed. This support will enable the P.I. to complete the development and testing of the software, including a "user-friendly" interface. The P.I. has already alerted the community to the existence of the Dynamic Clamp through a cover picture on the current issue of the Journal of Neurophysiology, and a report on its use. The P.I. has also established mechanisms for distribution and technical support of the software.***//
