A Neuropeptidergic Signaling Pathway for Olfactory Gain Modulation

Sensory systems are dynamically adjusted according to the animal’s ongoing needs by neuromodulators, such as neuropeptides. Despite their prevalence across all nervous systems[1][1],[2][2], how peptidergic neurons and the neuropeptide they release act to adjust sensory processing remains poorly understood. Here, we reveal that a heterogeneous ensemble of local interneurons (LNs) release the neuropeptide myoinhibitory peptide (MIP) within the Drosophila primary olfactory center (the antennal lobe, AL). We find MIPergic LNs form reciprocal connections with many AL principal neurons, but only a subset express the inhibitory MIP receptor (sex peptide receptor, SPR). We find both the MIPergic LNs and several of the SPR-expressing neurons are activated by the food-related odor apple cider vinegar (ACV), therefore suggesting MIP plays a role in adjusting ACV responses within the AL. We demonstrate that MIP can simultaneously decrease olfactory input to some glomeruli, while indirectly increasing olfactory input to others. As those glomeruli boosted by MIP – as well as MIP itself – are necessary and sufficient to initiate an attractive behavioral response to ACV[3][3],[4][4], the neural substrates identified here may represent a key circuit element for the animal’s switch in behavioral responses. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-4