Modeling Neural Mechanisms for Genesis of Respiratory Rhythm and Pattern:
I. Models of Respiratory Neurons.
Rybak, Ilya A., Julian F. R. Paton, and James S. Schwaber.
DuPont Central Research, E. I. du Pont de Nemours & Co., Experimental
Station E-0328, Wilmington, DE 19880-0328, USA; and Department of Physiology,
School of Medical Sciences, University of Bristol, University Walk, Bristol
BS8 1TD, UK.
APStracts 3:0252N, 1996.
The general objectives of our research, presented in this series of papers,
were to develop a computational model of the brainstem respiratory neural
network and to explore possible neural mechanisms that provide the genesis of
respiratory oscillations and the specific firing patterns of respiratory
neurons. The present paper describes models of single respiratory neurons
which have been used as the elements in our network models of the central
respiratory pattern generator presented in subsequent papers. The models of
respiratory neurons were developed in the Hodgkin-Huxley style employing both
physiological and biophysical data obtained from brainstem neurons in mammals.
Two single respiratory neuron models were developed to match the two distinct
firing behaviors of respiratory neurons described in vivo: neuron type I shows
an adapting firing pattern in response to synaptic excitation, and neuron type
II shows a ramp firing pattern during membrane depolarization following a
period of synaptic inhibition. We found that a frequency ramp firing pattern
can result from intrinsic membrane properties, specifically from the combined
influence of calcium dependent KAHP(Ca), low-threshold CaT and KA channels.
The neuron models with these ionic channels (type II) demonstrated ramp firing
patterns similar to those recorded from respiratory neurons in vivo. Our
simulations show that KAHP(Ca) channels in combination with high-threshold CaL
channels produce spike frequency adaptation during synaptic excitation.
However, in combination with low-threshold CaT channels, they cause a
frequency ramp firing response following release from inhibition. This
promotes a testable hypothesis that the main difference between the
respiratory neurons that adapt (for example, early-I, post-I and dec-E) and
those which show ramp firing patterns (for example, ramp-I and aug-E) consists
of a ratio between the two types of calcium channels: CaL channels predominate
in the former, whereas CaT channels prevail in the latter respiratory neuron
types. We have analyzed the dependence of adapting and ramp firing patterns on
maximal conductances of different ionic channels and values of synaptic drive.
The effect of adjusting specific membrane conductances and synaptic
interactions revealed plausible neuronal mechanisms that may underlie
modulatory effects on respiratory neuron firing patterns and network
performances. The results of computer simulation provide useful insight into
functional significance of specific intrinsic membrane properties and their
interactions with phasic synaptic inputs for a better understanding of
respiratory neuron firing behavior.
Received 8 April 1996; accepted in final form 12 December 1996.
APS Manuscript Number J284-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996