Bursting in Leech Heart Interneurons: Cell-Autonomous and Network-Based Mechanisms

Abstract

Rhythmic activity within the heartbeat pattern generator of the medicinal leech is based on the alternating bursting of mutually inhibitory pairs of oscillator heart interneurons (half-center oscillators). Bicuculline methiodide has been shown to block mutual inhibition between these interneurons and to cause them to spike tonically while recorded intracellularly (Schmidt and Calabrese, 1992). Using extracellular recording techniques, we show here that oscillator and premotor heart interneurons continue to burst when pharmacologically isolated with bicuculline, although the bursting is not robust in some preparations. We propose that a nonspecific leak current introduced by the intracellular microelectrode suppresses endogenous bursting activity to account for the discrepancy with results using intracellular recording. A two-parameter bifurcation diagram (E(leak) vs g(leak)) of a mathematical model of a single heart interneuron shows a narrow stripe of parameter values where bursting occurs, separating large zones of tonic spiking and silence. A similar analysis performed for a half-center oscillator model outlined a much larger area of bursting. Bursting in the half-center oscillator model is also less sensitive to variation in the maximal conductances of voltage-gated currents than in the single-neuron model. Thus, in addition to ensuring appropriate bursting characteristics such as period, phase, and duty cycles, the half-center configuration enhances oscillation robustness, making them less susceptible to random or imposed changes in membrane parameters. Endogenous bursting, in turn, ensures appropriate bursting if the strength of mutual inhibition is weakened and limits the minimum period of the half-center oscillator to a period near that of the single neuron.

Convergent Motor Patterns from Divergent Circuits

“…However, the PK-elicited gastric mill rhythm appears more appropriately defined as a hybrid CPG because, although it still relies on the reciprocal inhibition between LG and Int1, it also requires the intrinsic oscillatory activity of the AB neuron. The leech heartbeat CPG can also operate in either a network-based or intrinsic oscillatory mode (Cymbalyuk et al, 2002). However, in this latter system, there is a switch in the intrinsic properties of the same set of CPG neurons.…”

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

“…On a technical note, it has been observed that the "regular" rhythms computed numerically for the original HCO model are close to limit cycles but do not appear to fully converge [4]. There is a lack of continued damping of variability in the period, ISIs, etc.…”

“…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?…”

“…The existing, "full" version of the model will be denoted M F and has been developed over several studies. The version of the equations and parameters used here is described fully in [4], based on the model of Hill et al [5]. The form of the ordinary differential equation (ODE) for V is…”

The role of spiking and bursting pacemakers in the neuronal control of breathing

“…The activity pattern of autonomously active neurons can range from autonomously spiking to weak, irregular spiking and to regular bursting. The variety of activity patterns is explained by the ion channel diversity and the balance between inward and outward currents, a topic that has received considerable attention in invertebrate neurons [28][29][30]. Within the respiratory network two types of inward currents are particularly important in conferring autonomous activity patterns including bursting [26].…”