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

Author: mycolabadmin
9/28/2023
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Summary

This research reveals how two brain proteins called Spinophilin and Syd-1 work against each other to control how synapses strengthen during memory formation. When flies learn something new, these proteins reorganize the structure of synaptic connections through managing thin filaments called actin, which allows more neurotransmitters to be released. The study shows that this mechanism is essential for remembering information after learning, but not for the initial learning itself.

Background

Synapses undergo plastic changes that store information and adapt transmission strength, but the molecular mechanisms linking these changes to behavioral states remain incompletely understood. Presynaptic long-term plasticity has been observed in mammalian brains but its molecular regulation and behavioral relevance are enigmatic. This study investigates the conserved regulatory proteins Spinophilin and Syd-1 in controlling presynaptic plasticity.

Objective

The study aimed to elucidate how an antagonism between Spinophilin (Spn) and Syd-1 controls presynaptic long-term plasticity and memory maintenance in Drosophila. The researchers sought to identify upstream regulatory mechanisms governing active zone remodeling and their behavioral relevance in olfactory memory formation.

Results

Spn mutants failed to trigger active zone remodeling and sustain neurotransmitter release potentiation under homeostatic challenge, but concomitant reduction of Syd-1 rescued these deficits. The Spn/Syd-1 antagonism converged on F-actin dynamics at active zones, with actin depolymerization rescuing Spn deficits by enabling synaptic vesicle access to release sites. Within mushroom body neurons, the antagonism specifically controlled olfactory memory stabilization but not initial learning.

Conclusion

An evolutionarily conserved Spn/Syd-1 antagonism controls behaviorally relevant presynaptic long-term plasticity through F-actin remodeling and vesicle pool regulation. This mechanism is crucial for memory maintenance in olfactory learning while remaining dispensable for initial learning. The findings provide molecular insights into presynaptic plasticity mechanisms also observed in mammalian brains.

Published in:eLife,
Study Type:Basic Research,
Source: 10.7554/eLife.86084 / PMID: 37767892