Cross-modal modulation gates nociceptive inputs in Drosophila

Animals’ response to a stimulus in one sensory modality is usually influenced by other modalities.1 One important type of multisensory integration is the cross-modal modulation, in which one sensory modality modulates (typically inhibits) another. Identification of the mechanisms underlying cross-modal modulations is crucial for understanding how sensory inputs shape animals’ perception and for understanding sensory processing disorders.2,3,4 However, the synaptic and circuit mechanisms that underlie cross-modal modulation are poorly understood. This is due to the difficulty of separating cross-modal modulation from multisensory integrations in neurons that receive excitatory inputs from two or more sensory modalities5—in which case it is unclear what the modulating or modulated modality is. In this study, we report a unique system for studying cross-modal modulation by taking advantage of the genetic resources in Drosophila. We show that gentle mechanical stimuli inhibit nociceptive responses in Drosophila larvae. Low-threshold mechanosensory neurons inhibit a key second-order neuron in the nociceptive pathway through metabotropic GABA receptors on nociceptor synaptic terminals. Strikingly, this cross-modal inhibition is only effective when nociceptor inputs are weak, thus serving as a gating mechanism for filtering out weak nociceptive inputs. Our findings unveil a novel cross-modal gating mechanism for sensory pathways. [Display omitted] •Gentle mechanical stimuli inhibit nociceptive responses in Drosophila larvae•The cross-modal inhibition filters out only weak nociceptive inputs•Mechanosensory neurons inhibit A08n neurons in the nociceptive pathway•The cross-modal inhibition is mediated by GABAB receptors in nociceptors Pan et al. show that gentle mechanical stimuli inhibit nociceptive responses in Drosophila larvae. Due to the inhibition of a second-order neuron that responds to weak nociceptor inputs, this cross-modal inhibition is only effective when noxious cues are weak, thus serving as a mechanism to filter out weak nociceptive inputs.