An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
- Freie Universität Berlin, Germany
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Germany
Abstract
We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here we show that an antagonism between two conserved regulatory proteins, Spinophilin (Spn) and Syd-1, controls presynaptic long-term plasticity and the maintenance of olfactory memories in Drosophila. While Spn mutants could not trigger nanoscopic active zone remodeling under homeostatic challenge and failed to stably potentiate neurotransmitter release, concomitant reduction of Syd-1 rescued all these deficits. The Spn/Syd-1 antagonism converged on active zone close F-actin, and genetic or acute pharmacological depolymerization of F-actin rescued the Spn deficits by allowing access to synaptic vesicle release sites. Within the intrinsic mushroom body neurons, the Spn/Syd-1 antagonism specifically controlled olfactory memory stabilization but not initial learning. Thus, this evolutionarily conserved protein complex controls behaviorally relevant presynaptic long-term plasticity, also observed in the mammalian brain but still enigmatic concerning its molecular mechanisms and behavioral relevance.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all figures.
Article and author information
Author details
Janine Lützkendorf
Funding
Deutsche Forschungsgemeinschaft (EXC 2049 (#390688087))
- Stephan J Sigrist
Deutsche Forschungsgemeinschaft (TRR186/ A03 (#278001972))
- Stephan J Sigrist
Deutsche Forschungsgemeinschaft (NeuroNex2 (#436260754))
- Stephan J Sigrist
Deutsche Forschungsgemeinschaft (FOR5228 (#447288260))
- Stephan J Sigrist
European Research Council ([ERC-AdG Synprotect"]")
- Stephan J Sigrist
NanoSYNDIV (SI 849/10-1)
- Oriane Turrel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Ramesh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
eLife 12:e86084.
https://doi.org/10.7554/eLife.86084
