Pan, G., Li, R., Xu, G., Weng, S., Yang, X.L., Yang, L., Ye, B. (2023). Cross-modal modulation gates nociceptive inputs in Drosophila.  Curr. Biol. 33(7): 1372--1380.e4.

FBrf0256258

Research paper

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 modalities[5]-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.

PMC10089977 (PMC) (EuropePMC)