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An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity

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 a...

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Autores principales: Ramesh, Niraja, Escher, Marc, Turrel, Oriane, Lützkendorf, Janine, Matkovic, Tanja, Liu, Fan, Sigrist, Stephan J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588984/
https://www.ncbi.nlm.nih.gov/pubmed/37767892
http://dx.doi.org/10.7554/eLife.86084
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author Ramesh, Niraja
Escher, Marc
Turrel, Oriane
Lützkendorf, Janine
Matkovic, Tanja
Liu, Fan
Sigrist, Stephan J
author_facet Ramesh, Niraja
Escher, Marc
Turrel, Oriane
Lützkendorf, Janine
Matkovic, Tanja
Liu, Fan
Sigrist, Stephan J
author_sort Ramesh, Niraja
collection PubMed
description 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.
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spelling pubmed-105889842023-10-21 An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity Ramesh, Niraja Escher, Marc Turrel, Oriane Lützkendorf, Janine Matkovic, Tanja Liu, Fan Sigrist, Stephan J eLife Neuroscience 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. eLife Sciences Publications, Ltd 2023-09-28 /pmc/articles/PMC10588984/ /pubmed/37767892 http://dx.doi.org/10.7554/eLife.86084 Text en © 2023, Ramesh et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Ramesh, Niraja
Escher, Marc
Turrel, Oriane
Lützkendorf, Janine
Matkovic, Tanja
Liu, Fan
Sigrist, Stephan J
An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
title An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
title_full An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
title_fullStr An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
title_full_unstemmed An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
title_short An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
title_sort antagonism between spinophilin and syd-1 operates upstream of memory-promoting presynaptic long-term plasticity
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588984/
https://www.ncbi.nlm.nih.gov/pubmed/37767892
http://dx.doi.org/10.7554/eLife.86084
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