COMPUTATIONAL MODELING AND SIMULATION AS ENABLERS FOR BIOLOGICAL DISCOVERY 181
PANEL 2FIGURE 5.16 Continued
Panel 2: Gating and I-V characteristics of components of models 1 and 2. (A) spike-generating kinetics: m∞^3 (V) and
h∞(V) of INa and n∞(V) and τn(V) of IK; note that h=1− n. (B1) gating characteristics of INaP: m∞(V), h∞(V), and τh(V)
(bold); left: y-axis scale for steady-state gating functions; right: y-axis scale for τh(V). (B2) I-V plots of INaP for
h=h∞(V) and h=1. First case results in a small window current at subthreshold potentials; second case corre-
sponds to INaP-h with complete removal of inactivation. (C1) gating characteristics of IKS: k∞(V) and τk(V) (bold);
left: y-axis scale for activation function; right: y-axis scale for τk(V). (C2) I-V plots of INaP+IKS for k=k∞(V) and
k=0. First case results in a small current at subthreshold potentials; second case corresponds to INaP with com-
plete removal of the opposing IKS.
SOURCE: Reprinted by permission from R.J. Butera, Jr., J. Rinzel, and J.C. Smith, “Models of Respiratory Rhythm
Generation in the Pre-Bötzinger Complex. I. Bursting Pacemaker Neurons,” Journal of Neurophysiology 82(1):382-
397, 1999. Copyright 1999 American Physiological Society.
ing rhythms displayed by this model are shown in the second panel. The third panel shows a map of the
simulated trajectory that illustrates the relationship of the bursting to slow and fast variables in the
system.
5.4.5.4 Synaptic Transmission
The intercellular signaling process of synaptic transmission is a much-studied problem. Much has
been learned about synaptic structure and function through the classical techniques of neuropharma-
cology, electron microscopy (EM) neuroanatomy, and electrophysiology, and correlation of the obser-
vations made through these various techniques has led to the development of computational models of
synaptic microphysiology. However, the scope of previous modeling attempts has been limited by
available computing power, modeling framework, and lack of high-resolution three-dimensional ultra-
structural data in an appropriate machine representation.