Hybrid Systems Analysis of the Control of Burst Duration by Low-Voltage-Activated Calcium Current in Leech Heart Interneurons

Abstract

Olypher, Andrey, Gennady Cymbalyuk, and Ronald L. Calabrese. Hybrid systems analysis of the control of burst duration by low-voltage-activated calcium current in leech heart interneurons. J Neurophysiol 96: 2857-2867. First published August 30, 2006 doi:10.1152/jn.00582.2006. The leech heartbeat CPG is paced by the alternating bursting of pairs of mutually inhibitory heart interneurons that form elemental half-center oscillators. We explore the control of burst duration in heart interneurons using a hybrid system, where a living, pharmacologically isolated, heart interneuron is connected with artificial synapses to a model heart interneuron running in real-time, by focusing on a low-voltage-activated (LVA) calcium current I CaS . The transition from silence to bursting in this half-center oscillator occurs when the spike frequency of the bursting interneuron declines to a critical level, f Final , at which the inhibited interneuron escapes owing to a build-up of the hyperpolarization-activated cation current, I h . We varied I CaS inactivation time constant either in the living heart interneuron or in the model heart interneuron. In both cases, varying I CaS inactivation time constant did not affect f Final of either interneuron, but in the varied interneuron, the time constant of decline of spike frequency during bursts to f Final and thus the burst duration varied directly and nearly linearly with I CaS inactivation time constant. Bursts of the opposite, nonvaried interneuron did not change. We show also that control of burst duration by I CaS inactivation does not require synaptic interaction by reconstituting autonomous bursting in synaptically isolated living interneurons with injected I CaS . Therefore inactivation of LVA calcium current is critically important for setting burst duration and thus period in a heart interneuron half-center oscillator and is potentially a general intrinsic mechanism for regulating burst duration in neurons.

Na+/K+ pump interacts with the h-current to control bursting activity in central pattern generator neurons of leeches

“…Previous studies in other systems have suggested that the h -current might counteract the hyperpolarizing effects of the pump current (e.g., Robert and Jirounek, 1998; Soleng et al, 2003; Baginskas et al, 2009). Moreover, Hill et al (2001) developed a canonical model of the oscillator heart interneurons and showed that increasing the h -current conductance decreases the period, which was later supported by dynamic clamp experiments (Sorensen et al, 2004; Olypher et al, 2006). Using a hybrid half-center oscillator, Sorensen et al (2004) found that increasing the h -current conductance of living or silicon neurons with dynamic clamp decreases the period and interburst interval, without affecting the burst duration.…”

The neural control of heartbeat in invertebrates

“…I CaS drives the burst phase slowly inactivating to release, as spike rate wanes, the opposite inhibited neuron of the half-center oscillator, while the I h activated by the hyperpolarization associated with inhibition, which also removes inactivation from I CaS ), drives the inhibited neuron of the HCO toward escape and burst formation. This mixed escape-release model for rhythmicity in a half-center microcircuit has been repeatedly corroborated by modeling [29,34–36] and dynamic-clamp studies [37,38]. The endogenous peptide myomodulin speeds the burst rhythm of the two HCOs by up-modulating I h and down modulating the current driven by the Na + /K + pump [39].…”

Inferring and quantifying the role of an intrinsic current in a mechanism for a half-center bursting oscillation

“…Previous studies of this HCO model and electrophysiological studies of the leech heartbeat have addressed fundamental questions about the mechanism of bursting [4,5,[13][14][15][16][17]. Regarding I h specifically, these questions can be summarized in terms of roles: R1: What role does I h have in the existence of a stable HCO rhythm?…”