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

Atefeh Pooryasin,André Fiala,Marco Schubert,Ulrike Pech,Stephan J. Sigrist,Marta Maglione,Tanja Matkovic-Rachid,Sayed-mohammad Hasheminasab,Thorsten Mielke

doi:10.1038/s41467-021-22180-6

Abstract

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.

Highlights

The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP)
Synaptic transmission in turn relies on the rapid fusion of neurotransmitter-containing synaptic vesicles (SVs), which happens in response to action potentials (APs)-induced Ca2+ influx at active zones (AZs)
We further found that the Unc13B-mediated transmission component in inhibitory projection neurons operated antagonistically to Unc13B in excitatory projection neuron (ePN), making the convergence region of both ePNs and iPNs, called lateral horn (LH), the likely place of signal integration here

Summary

Introduction

The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors triggering the release of neurotransmitter-containing vesicles regulates short-term plasticity (STP). Repetitive activation can lead to either strengthening or weakening of transmission, resulting in a rather tonic or phasic filtering characteristic This “short-term plasticity” (STP), referring to use-dependent changes in synapse strength on time scales of tens to hundreds of milliseconds, has been demonstrated to be highly diversified across the brain synapses of experimental mammals[1,2,3]. Biophysical and electrophysiological analyses suggest that both release probability and STP depend greatly on the nanometer scale distance between SVs with their Ca2+ sensor synaptotagmin, and VGCCs3,5–9 This is explained by the sharp spatiotemporal profile of AP‐induced Ca2+ transients and by the fact that SV fusion is activated by the cooperative binding of several (3–5) Ca2+ ions, resulting in a strong distance relationship for release probability: SVs positioned closer to the Ca2+ source have much higher release probabilities than distant ones. At the first relay synapse of the Drosophila olfactory system uniquely amenable to electrophysiological analysis across Drosophila brain synapses, Unc13A promotes a high probability but depressing phasic, while Unc13B a slower tonic release component[12]

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Results

Conclusion