PubMed Health⌕ Search

Biomedical subjects

Andrew A V Hill

Publications and source records attributed to Andrew A V Hill.

4 recordsLinked to original sources

Detailed model of intersegmental coordination in the timing network of the leech heartbeat central pattern generator.

To address the general problem of intersegmental coordination of oscillatory neuronal networks, we have studied the leech heartbeat central pattern generator. The core of this pattern generator is a timing network that consists of two segmental oscillators, each of which comprises two identified, reciprocally inhibitory oscillator interneurons. Intersegmental coordination between the segmental oscillators is mediated by synaptic interactions between the oscillator interneurons and identified coordinating interneurons. The small number of neurons (8) and the distributed structure of the timing network have made the experimental analysis of the segmental oscillators as discrete, independent units possible. On the basis of this experimental work, we have made conductance-based models to explore how intersegmental phase and cycle period are determined. We show that although a previous simple model, which ignored many details of the living system, replicated some essential features of the living system, the incorporation of specific cellular and network properties is necessary to capture the behavior of the system seen under different experimental conditions. For example, spike frequency adaptation in the coordinating interneurons and details of asymmetries in intersegmental connectivity are necessary for replicating driving experiments in which one segmental oscillator was injected with periodic current pulses to entrain the activity of the entire network. Nevertheless, the basic mechanisms of phase and period control demonstrated here appear to be very general and could be used by other networks that produce coordinated segmental motor outflow.

Action Potentials↗

Heartbeat control in leeches. II. Fictive motor pattern.

The rhythmic beating of the tube-like hearts in the medicinal leech is driven and coordinated by rhythmic activity in segmental heart motor neurons. The motor neurons are controlled by rhythmic inhibitory input from a network of heart interneurons that compose the heartbeat central pattern generator. In the preceding paper, we described the constriction pattern of the hearts in quiescent intact animals and showed that one heart constricts in a rear-to-front wave (peristaltic coordination mode), while the other heart constricts in near unison over its length (synchronous coordination mode) and that they regularly switch coordination modes. Here we analyze intersegmental and side-to-side-coordination of the fictive motor pattern for heartbeat in denervated nerve cords. We show that the intersegmental phase relations among heart motor neurons in both coordination modes are independent of heartbeat period. This finding enables us to combine data from different experiments to form a detailed analysis of the relative phases, duty cycle, and intraburst spike frequency of the bursts of the segmental heart motor neurons. The fictive motor pattern and the constriction pattern seen in intact leeches closely match in their intersegmental and side-to-side coordination, indicating that sensory feedback is not necessary for properly phased intersegmental coordination. Moreover, the regular switches in coordination mode of the fictive motor pattern mimic those seen in intact animals indicating that these switches likely arise by a central mechanism.

Action Potentials↗

Model of intersegmental coordination in the leech heartbeat neuronal network.

We have created a computational model of the timing network that paces the heartbeat of the medicinal leech, Hirudo medicinalis. The rhythmic activity of this network originates from two segmental oscillators located in the third and fourth midbody ganglia. In the intact nerve cord, these segmental oscillators are mutually entrained to the same cycle period. Although experiments have shown that the segmental oscillators are coupled by inhibitory coordinating interneurons, the underlying mechanisms of intersegmental coordination have not yet been elucidated. To help understand this coordination, we have created a simple computational model with two variants: symmetric and asymmetric. In the symmetric model, neurons within each segmental oscillator called oscillator interneurons, inhibit the coordinating interneurons. In contrast, in the asymmetric model only the oscillator interneurons of one segmental oscillator inhibit the coordinating interneurons. In the symmetric model, when two segmental oscillators with different inherent periods are coupled, the faster one leads in phase, and the period of the coupled system is equal to the period of the faster oscillator. This behavior arises because, during each oscillation cycle, the oscillator interneurons of the faster segmental oscillator begin to burst before those of the slower oscillator, thereby terminating spike activity in the coordinating interneurons. Thus there is a brief period of time in each cycle when the oscillator interneurons of the slower segmental oscillator are relieved of inhibition from the coordinating interneurons. This "removal of synaptic inhibition" allows, within certain limits, the slower segmental oscillator to be sped to the period of the faster one. Thus the symmetric model demonstrates a plausible biophysical mechanism by which one segmental oscillator can entrain the other. In general the asymmetric model, in which only one segmental oscillator has the ability to inhibit the coordinating interneurons, behaves similarly, except only one segmental oscillator can control the period of the system. In addition, we simulated physiological experiments in which a "driving" stimulus, consisting of alternating positive and negative current steps, was used to control a single oscillator interneuron and thereby entrain the activity of the entire timing network.

Action Potentials↗