Unc13A and Unc13B contribute to the decoding of distinct sensory information in Drosophila

Nat Commun. 2021 Mar 26;12(1):1932. doi: 10.1038/s41467-021-22180-6.


The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP). While STP is highly diversified across synapse types, the computational and behavioral relevance of this diversity remains unclear. In the Drosophila brain, at nanoscale level, we can distinguish distinct coupling distances between Ca2+ channels and the (m)unc13 family priming factors, Unc13A and Unc13B. Importantly, coupling distance defines release components with distinct STP characteristics. Here, we show that while Unc13A and Unc13B both contribute to synaptic signalling, they play distinct roles in neural decoding of olfactory information at excitatory projection neuron (ePN) output synapses. Unc13A clusters closer to Ca2+ channels than Unc13B, specifically promoting fast phasic signal transfer. Reduction of Unc13A in ePNs attenuates responses to both aversive and appetitive stimuli, while reduction of Unc13B provokes a general shift towards appetitive values. Collectively, we provide direct genetic evidence that release components of distinct nanoscopic coupling distances differentially control STP to play distinct roles in neural decoding of sensory information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Appetitive Behavior / physiology
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Female
  • Interneurons / metabolism
  • Interneurons / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Interference
  • Synapses / metabolism
  • Synapses / physiology*
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism


  • Calcium Channels
  • Drosophila Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • unc-13 protein, Drosophila
  • Calcium