1 INTERFACING COMPUTER MODELS WITH REAL NEURONS: RESPIRATORY “CYBERNEURONS” CREATED WITH THE DYNAMIC CLAMP Christopher G. Wilson, Robert J. Butera, Jr., Christopher A. Del Negro, John Rinzel, and Jeffrey C. Smith * 1. INTRODUCTION The mechanism of respiratory rhythm generation remains an important unsolved problem. While experimental evidence has been collected about the location and distribution of respiratory neurons within the mammalian brainstem, only recently has the locus of rhythm generating neurons been discovered, 1 a functionally identified region of the brainstem known as the Pre-Bötzinger complex (pre-BötC). We’ve just begun to investigate the membrane and network properties of pre-BötC neurons underlying the generation and transmission of inspiratory rhythm. 2,3,4,5 We have proposed a pacemaker network model in which intrinsic membrane and synaptic conductances are responsible for inspiratory burst generation and synchroniza- tion of pacemaker neurons in the pre-BötC. 3,4 We have been exploring these mechanisms through two approaches. Our first approach relies on experimental evaluation of intrinsic and synaptic currents in pre-BötC neurons present in our in vitro, rhythmic slices. 1,2,5 Our second approach has been the use of mathematical models to evaluate hypotheses regarding the nature of the burst generating currents and synaptic coupling between neurons of the Pre-BötC. 3,4 We present our recently developed approach that combines experimental and computational methods to allow direct interfacing of computer models with real neurons to explore cellular and network properties of the pre-BötC. Within the last decade, a few investigators have made efforts to combine electrophysiology techniques with computational modeling, to develop a method of dynamically adding currents representing artificial chemical and electrical synapses into single neurons or small neural networks. 6,7 Typically, the added current is calculated based on a mathematical model of a synapse or ionic conductance. These “dynamic *Christopher G. Wilson, Christopher A. Del Negro, and Jeffrey C. Smith, Cellular and Systems Neurobiology Section, NINDS, NIH, Bethesda, Maryland, 20892. Robert J. Butera, Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, 30332. John Rinzel, Center for Neural Science and Courant Institute of Mathematical Science, New York University, New York, 10013.