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

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.

SNARE Regulatory Proteins in Synaptic Vesicle Fusion and Recycling

“…Given presynaptic output and plasticity mechanisms display wide heterogeneity across neuronal subtypes and at individual release sites, SRPs are likely subject to transcriptional and post-translational control that alters their function. Indeed, SRPs can regulate release differences by controlling SV availability, spontaneous release rate, and SV priming location (Hu et al, 2013;Melom et al, 2013;Cho et al, 2015;Böhme et al, 2016;Fulterer et al, 2018;Aponte-Santiago and Littleton, 2020;Pooryasin et al, 2021).…”

“…Similarly, the synaptic levels of Unc18 and Syx1 are finely tuned to regulate SV priming dynamics that are required to support presynaptic homeostatic plasticity at Drosophila NMJs (Ortega et al, 2018). Alternative splicing of Unc13 in Drosophila and C. elegans results in unique isoforms that alter the protein's length, allowing the MUN domain to position and control SV priming at varying distances from AZ Ca 2+ channel clusters (Hu et al, 2013;Böhme et al, 2016;Reddy-Alla et al, 2017;Fulterer et al, 2018;Pooryasin et al, 2021). In Drosophila, newly formed AZs first accumulate the long Unc13B splice variant before the shorter Unc13A variant arrives as AZs mature.…”

Homeostatic Synaptic Plasticity Rescues Neural Coding Reliability

“…Here parallels may exist with the NMJ, where the expression of presynaptic homeostatic plasticity is compartmentalized to a subset of a motoneuron’s synapses depending on their target muscle (Li et al, 2018). These considerations emphasize the importance of further future studies on the molecular heterogeneity of AZs in the olfactory system (Ehmann et al, 2018; Fulterer et al, 2018; Pooryasin et al, 2021) and of elucidating the physiological properties of individual synapses in the context of neural information processing.…”

(M)Unc13s in Active Zone Diversity: A Drosophila Perspective

“…A three-channel two-dimensional timegated STED (gSTED) imaging on PN-derived AZs in the lateral horn (LH) showed that Unc13A localized at about 60 nm relative to the AZ center, and the B isoform spots were still found at further distances at inhibitory PN (iPN) output synapses. These were the same as the coupling distances at the terminals of cholinergic excitatory PN (ePN) in the LH (Pooryasin et al, 2021).…”