Comodulation reduces interindividual variability of circuit output.

Behaviors as simple as reflexes or as complex as physiological responses to psychedelics can vary significantly among individuals, even when accounting for genotype and other variables. This behavioral variability results largely from variability of underlying neural circuits. Yet, in most cases, the CNS precisely controls behavior, and significant variability in CNS output may result in outputs deemed dysfunctional. We propose that additive actions of neuromodulators that target the same subcellular targets (comodulation) plays a central role in ensuring that neural circuits produce consistent circuit output in the face of extensive inter-individual variability.