Modeling a Neural Oscillator that Paces Heartbeat in the Medicinal Leech

Abstract
SYNOPSIS. Heartbeat in the medicinal leech is paced by a neural oscillator comprising two elemental oscillators whose activity is coordinated intersegmental coordinating fibers. The elemental oscillators each consist of a bilateral pair of heart interneurons linked by reciprocal inhibitory synapses. The activity cycle of each elemental oscillator consists of alternating bursts of action potentials (plateau/burst phase) and periods inhibition (inactive phase). Oscillation ensues in the reciprocally inhibitory pairs because each neuron is able to escape from the inhibition its contralateral partner and thus move on to the plateau/burst phase. We have identified and described membrane currents that contribute to oscillation and studied graded synaptic transmission between the neurons, using discontinuous current clamp and switching single electrode voltage clamp techniques. A hyperpolarization-activated inward current, Ih, plays a major role in escape from inhibition, and Ca2+ currents produce plateau potentials that support burst formation and mediate graded synaptic transmission. To consolidate our knowledge and guide future research, we have constructed a first generation computer model of a neural oscillator based on reciprocal inhibition, using Hodgkin-Huxley equations and a synaptic transfer model, derived from our biophysical studies, with Nodus software (De Schutter, 1989). This model has confirmed an important role for Ih in sustaining oscillation and has implicated a similarly important role for outward currents (particularly IA), which remain to be studied. Neural oscillators based on reciprocal inhibition appear to be ubiquitous, and our studies, biophysical and computational, provide insights into how they may operate.