Differential modulation of feedforward inhibition reflects topographic organization in the olfactory system

Nat Commun. 2025 Dec 16;16(1):11165. doi: 10.1038/s41467-025-66107-x.

Abstract

The nervous system flexibly processes information under different conditions. To do this, neural networks frequently rely on uniform expression of modulatory receptors by distinct classes of neurons to fine tune the computations supported by each neuronal class. Here, we explore an alternate organization in which one population of neurons in the olfactory system of Drosophila expresses all of the receptors for the modulator serotonin. We find extensive, heterogeneous receptor co-expression by ventral projection neurons (v-PNs), with many receptor combinations present. Despite overlap in glomerular innervation of v-PNs expressing each serotonin receptor, their axon terminals innervate largely distinct zones within a higher order olfactory region. Serotonin differentially modulates odor-evoked responses of v-PNs with distinct receptor expression and these v-PNs synapse upon separate sets of third order olfactory neurons. This functional organization implies that serotonin differentially modulates the responses of v-PNs that participate in divergent, downstream olfactory circuits.

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster* / physiology
  • Odorants
  • Olfactory Pathways* / cytology
  • Olfactory Pathways* / metabolism
  • Olfactory Pathways* / physiology
  • Olfactory Receptor Neurons* / metabolism
  • Olfactory Receptor Neurons* / physiology
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism
  • Smell / physiology
  • Synapses / metabolism

Substances

  • Serotonin
  • Drosophila Proteins
  • Receptors, Serotonin