Context-dependent modulation reconfigures interactive sensory-mediated microcircuits in Caenorhabditis elegans

•Sensory neurons are polymodal and extensively interconnected.•Neuromodulators mediate feedback loops and crosstalk among synaptic partners.•Local/humoral monoaminergic signaling facilitates long-term, system-wide modulation.•Extrasynaptic monoaminergic modulation is focused by synaptic peptidergic signaling.•Neuromodulators ‘functionally reconfigure’ anatomically defined microcircuits.

Caenorhabditis elegans navigates sensory landscapes by integrating inputs from 14 pairs of polymodal sensory neurons. Sensory neurons interact synaptically and through gap junction networks and are modulated by complex local/humoral, nutritionally dependent, monoaminergic and peptidergic signaling cascades that dynamically reconfigure individual sensory-mediated locomotory circuits. Monoaminergic/peptidergic signaling modifies the sensory signal by providing, first, feedback loops between sensory neurons and postsynaptic partners to fine tune inputs, second, crosstalk between sensory neurons to integrate responses and third, local/humoral extrasynaptic signals to facilitate broader, long term system-wide modulation. Overall, these observations highlight the differences between an anatomical wiring diagram and ‘functional connectomes’ that are essential to generate the alternative circuit configurations required to choose different behavioral outcomes in the face of changing environmental inputs.