Animal-to-animal variability of connection strength in the leech heartbeat central pattern generator.

The heartbeat central pattern generator (CPG) in medicinal leeches controls blood flow within a closed circulatory by programming the constrictions of two parallel heart tubes. This circuit reliably produces a stereotyped fictive pattern of activity and has been extensively characterized. Here we determined, as quantitatively as possible, the strength of each inhibitory synapse and electrical junction within the core circuit of the heartbeat CPG. We also examined the animal-to-animal variability in strengths of these connections and, for some, determined the correlations between connections to the same postsynaptic target. The core CPG is composed of seven bilateral pairs of heart interneurons connected via both inhibitory chemical synapses and electrical junctions. Fifteen different connections within the core CPG were measured for strength using extracellular presynaptic recordings and postsynaptic voltage-clamp recordings across a minimum of seven individuals each, and the animal-to-animal variability was characterized. Connection strengths within the core network varied three to more than sevenfold among individuals (depending on the specific connection). The balance between two inputs onto various postsynaptic targets was explored by within-individual comparisons and correlation across individuals. Of the seven comparisons made within the core CPG, three showed a clear correlation of connection strengths, while the other four did not. We conclude that the leech heartbeat CPG can withstand wide variability in connection strengths and still produce stereotyped output. The network appears to preserve the relative strengths of some pairs of inputs, despite the animal-to-animal variability.

A role for compromise: synaptic inhibition and electrical coupling interact to control phasing in the leech heartbeat CpG.

How can flexible phasing be generated by a central pattern generator (CPG)? To address this question, we have extended an existing model of the leech heartbeat CPG's timing network to construct a model of the CPG core and explore how appropriate phasing is set up by parameter variation. Within the CPG, the phasing among premotor interneurons switches regularly between two well defined states - synchronous and peristaltic. To reproduce experimentally observed phasing, we varied the strength of inhibitory synaptic and excitatory electrical input from the timing network to follower premotor interneurons. Neither inhibitory nor electrical input alone was sufficient to produce proper phasing on both sides, but instead a balance was required. Our model suggests that the different phasing of the two sides arises because the inhibitory synapses and electrical coupling oppose one another on one side (peristaltic) and reinforce one another on the other (synchronous). Our search of parameter space defined by the strength of inhibitory synaptic and excitatory electrical input strength led to a CPG model that well approximates the experimentally observed phase relations. The strength values derived from this analysis constitute model predictions that we tested by measurements made in the living system. Further, variation of the intrinsic properties of follower interneurons showed that they too systematically influence phasing. We conclude that a combination of inhibitory synaptic and excitatory electrical input interacting with neuronal intrinsic properties can flexibly generate a variety of phase relations so that almost any phasing is possible.