Comodulation reduces interindividual variability of circuit output.

Area of Science:

• Neuroscience
• Computational Neuroscience
• Systems Neuroscience

Background:

• Neural circuit output exhibits remarkable consistency despite substantial inter-individual variation in ionic current levels.
• Neuromodulators provide flexibility to neural circuits, often with overlapping actions but neuron-specific effects due to distinct receptor expression.
• Convergent neuromodulators acting on common downstream targets can potentially enhance uniformity across individuals.

Approach:

• The pyloric circuit of the crab Cancer borealis was used to test the hypothesis that comodulation reduces inter-individual variability.
• Inter-individual variability of the unmodulated pyloric circuit was quantified by measuring activity phases, cycle frequency, and spike properties.
• The effect of different combinations and concentrations of three neuropeptides on circuit output variability was examined.

Key Points:

• Comodulation by multiple neuropeptides significantly reduced pyloric circuit output variability at a mid-level concentration (30 nM).
• This reduction in variability was not observed at near-threshold (1 nM) or saturating (1 μM) concentrations.
• Comodulation did not reduce the inter-individual variability of response properties in isolated neurons.

Conclusions:

• A baseline tonic level of comodulation by convergent neuromodulators can decrease inter-individual variability in neural circuit output.
• The reduction in output variability appears to be an emergent network effect rather than a property of individual neurons.
• This finding highlights a mechanism for achieving robust neural function in the face of biological variability.