Constancy and Variability in the Output of a Central Pattern Generator

Abstract

Experimental and corresponding modeling studies have demonstrated a 2–5 fold variation of intrinsic and synaptic parameters across animals, while functional output is maintained. These studies have led to the hypothesis that correlated, compensatory changes in particular parameters can at least partially explain the biological variability in parameters. Using the leech heartbeat CPG, we selected three different segmental motor neurons that fire in a functional phase progression but receive input from the same four premotor interneurons. Previous work suggested that the phase progression arises because the pattern of relative strength of the four inputs varies systematically across the segmental motor neurons. Nevertheless, there was considerable animal-to-animal variation in the absolute strengths of these connections. We tested the hypothesis that functional output is maintained in the face of variation in the absolute strength of connections because relative strengths onto particular motor neurons are maintained. We found relative strength is not strictly maintained across animals even as functional output is maintained, and animal-to-animal variations in relative strength of particular inputs do not correlate strongly with output phase. In parallel with this variation in synaptic strength, the firing phase of the premotor inputs to these motor neurons varies considerably across individuals. We conclude that the number (four) of inputs to each motor neuron, which each vary in strength, and the phase diversity of the temporal pattern of input from the CPG diminish the influence of individual inputs. We hypothesize that each animal arrives at a unique solution for how the network produces functional output.

Contribution of motoneuron intrinsic properties to fictive motor pattern generation

“…In the pyloric network of the stomatogastric system, for example, the onset of the LP motoneuron is correlated to the synaptic conductance of each of its inputs from the pacemaker kernel, the AB/PD complex (Goaillard et al 2009). We do not see such correlations between single inputs and output phase in our system (Norris et al 2011), suggesting that there may be a more complex interaction between elements of the premotor synaptic conductance pattern and the heart motoneuron intrinsic properties.…”

“…Across segments, heart motoneurons receiving the peristaltic pattern of synaptic input show phasing similar to the ensemble model. We do not attribute these discrepancies to experimental or procedural errors; furthermore, all of the appropriate inputs are accounted for in the segmental input patterns that were used in our model and dynamic clamp experiments (Norris et al 2011). A modulatory extrinsic input, acting on a cycle-by-cycle basis, may contribute to peristaltic phasing, but as of yet no such inputs have been identified in the leech.…”

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

“…Previous work on the pyloric network of the crustacean STN Schulz et al 2006;Schulz et al 2007) and on the inhibitory synaptic inputs to leech heart motoneurons (Norris et al 2007a;Norris et al 2011) has demonstrated a two-to fivefold animal-to-animal variability in intrinsic properties and/or in synaptic strengths, yet with functional circuit output. In this study, we uncovered an apparently much wider range of variability in synaptic strengths, with some connections in the core leech heartbeat CPG varying greater than sevenfold in strength across individuals.…”

“…If the total complement of input onto an HN(4) oscillator interneuron is the critical factor in balancing the strengths of its inputs, then this lack of correlation may be due to the incompleteness of our comparison, c.f. Norris et al (2011).…”

“…The leech heartbeat system has been described in detail (Kristan et al 2005;Norris et al 2006;Norris et al 2007a;b;Norris et al 2011;Wenning et al 2011), so we briefly summarize here. Blood flow in the medicinal leech is driven by the rhythmic constriction of a bilateral pair of heart tubes, with one heart tube constricting with a rear-tofront pattern (i.e., peristaltic), while the other heart tube constricts nearly synchronously along most of its length (i.e., synchronous) (Wenning et al 2004a;Wenning and Meyer 2007).…”