Heartbeat control in the medicinal leech: A model system for understanding the origin, coordination, and modulation of rhythmic motor patterns

Abstract

We have analyzed in detail the neuronal network that generates heartbeat in the leech. Reciprocally inhibitory pairs of heart interneurons form oscillators that pace the heartbeat rhythm. Other heart interneurons coordinate these oscillators. These coordinating interneurons, along with the oscillators interneurons, form an eight-cell timing oscillator network for heartbeat. Still other interneurons, along with the oscillator interneurons, inhibit heart motor neurons, sculpting their activity into rhythmic bursts. Critical switch interneurons interface between the oscillator interneurons and the other premotor interneurons to produce two alternating coordination states of the motor neurons. The periods of the oscillator interneurons are modulated by endogenous RFamide neuropeptides. We have explored the ionic currents and graded and spike-mediated synaptic transmission that promote oscillation in the oscillator interneurons and have incorporated these data into a conductance-based computer model. This model has been of considerable predictive value and has led to new insights into how reciprocally inhibitory neurons produce oscillation. We are now in a strong position to expand this model upward, to encompass the entire heartbeat network, horizontally, to elucidate the mechanisms of FMRFamide modulation, and downward, to incorporate cellular morphology. By studying the mechanisms of motor pattern formation in the leech, using modeling studies in conjunction with parallel physiological experiments, we can contribute to a deeper understanding of how rhythmic motor acts are generated, coordinated, modulated, and reconfigured at the level of networks, cells, ionic currents, and synapses.

Hemodynamics in the leech: blood flow in two hearts switching between two constriction patterns

“…coordination, timing and switching between the peristaltic and the synchronous mode (Maranto and Calabrese, 1984a;Maranto and Calabrese, 1984b). The heart motor neurons are in turn driven by a well-studied heartbeat central pattern generator (for reviews, see Calabrese et al, 1995;Kristan et al, 2005).…”

Phase Relationships Between Segmentally Organized Oscillators in the Leech Heartbeat Pattern Generating Network

“…The core timing network of the heartbeat central pattern generator of the leech has been characterized as comprising two coupled segmental oscillators (Calabrese et al 1995;Peterson 1983a,b). This network has been described in cellular detail (Calabrese et al 1995), and thus it affords an opportunity for a cellular analysis of the mechanisms underlying coordination between coupled oscillators.…”

“…This network has been described in cellular detail (Calabrese et al 1995), and thus it affords an opportunity for a cellular analysis of the mechanisms underlying coordination between coupled oscillators. We undertake this analysis in three stages.…”

A Slow Outward Current Activated by FMRFamide in Heart Interneurons of the Medicinal Leech

“…We have been studying the pattern generator for heartbeat in the medicinal leech and its modulation by the endogenous (Evans et al, 1991) neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH 2 ) (for a recent review, see Calabrese et al, 1995). Activity in the FMRFamide immunoreactive cell 204 or bath application of the peptide (Յ5 ϫ 10 Ϫ8 M) increases the cycle rate of this pattern generator (Simon et al, 1992).…”