Neural circuits can generate many spike patterns, but only some are functional. The study of how circuits generate and maintain functional dynamics is hindered by a poverty of description of circuit dynamics across functional and dysfunctional states. For example, although the regular oscillation of a central pattern generator is well characterized by its frequency and the phase relationships between its neurons, these metrics are ineffective descriptors of the irregular and aperiodic dynamics that circuits can generate under perturbation or in disease states. By recording the circuit dynamics of the well-studied pyloric circuit in Cancer borealis, we used statistical features of spike times from neurons in the circuit to visualize the spike patterns generated by this circuit under a variety of conditions. This approach captures both the variability of functional rhythms and the diversity of atypical dynamics in a single map. Clusters in the map identify qualitatively different spike patterns hinting at different dynamical states in the circuit. State probability and the statistics of the transitions between states varied with environmental perturbations, removal of descending neuromodulatory inputs, and the addition of exogenous neuromodulators. This analysis reveals strong mechanistically interpretable links between complex changes in the collective behavior of a neural circuit and specific experimental manipulations, and can constrain hypotheses of how circuits generate functional dynamics despite variability in circuit architecture and environmental perturbations.

Ionic current levels of identified neurons vary substantially across individual animals. Yet, under similar conditions, neural circuit output remains remarkably similar, particularly in motor circuits. At any time, a neural circuit is influenced by multiple neuromodulators which provide flexibility to its output. These neuromodulators often overlap in their actions by modulating the same channel type or synapse yet have neuron-specific actions resulting from distinct receptor expression. With multiple neuromodulators, however, a common target is more uniformly activated across neurons. We propose that a baseline tonic (non-saturating) level of comodulation by convergent neuromodulators can reduce interindividual variability of circuit output. We tested this hypothesis in the pyloric circuit of the crab Cancer borealis. Multiple excitatory neuropeptides converge to activate the same voltage-gated inward current in this circuit, but different subsets of pyloric neurons have receptors for each peptide. We quantified the interindividual variability of the unmodulated pyloric circuit output by measuring the activity phases, cycle frequency and within-burst spike number and frequency. We then examined the variability in the presence of different combinations and concentrations of three excitatory neuropeptides. We found that at mid-level concentration (30 nM) but not at near-threshold (1 nM) or saturating (1 μM) concentrations, comodulation by multiple neuropeptides reduced the circuit output variability. Notably, the output variability of an isolated neuron was not reduced by comodulation at the mid-level concentration. Therefore, the reduction of circuit output variability is not due to a simple reduction of the variability of individual neuron excitability but emerges as a network effect.

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