
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.10.612361
preprint
1
Article
Distinct input-specific mechanisms enable presynaptic homeostatic plasticity
Chien Chun
He Kaikai
Perry Sarah
Tchitchkan Elizabeth
Han Yifu
Li Xiling
Dickman Dion http://orcid.org/0000-0003-1884-284X

12 9 2024
2024.09.10.612361https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.10.612361
nihpp-2024.09.10.612361.pdf
ABSTRACT

Synapses are endowed with the flexibility to change through experience, but must be sufficiently stable to last a lifetime. This tension is illustrated at the Drosophila neuromuscular junction (NMJ), where two motor inputs that differ in structural and functional properties co-innervate most muscles to coordinate locomotion. To stabilize NMJ activity, motor neurons augment neurotransmitter release following diminished postsynaptic glutamate receptor functionality, termed p resynaptic h omeostatic p otentiation (PHP). How these distinct inputs contribute to PHP plasticity remains enigmatic. We have used a botulinum neurotoxin to selectively silence each input and resolve their roles in PHP, demonstrating that PHP is input-specific: Chronic (genetic) PHP selectively targets the tonic MN-Ib, where active zone remodeling enhances Ca 2+ influx to promote increased glutamate release. In contrast, acute (pharmacological) PHP selectively increases vesicle pools to potentiate phasic MN-Is. Thus, distinct homeostatic modulations in active zone nanoarchitecture, vesicle pools, and Ca 2+ influx collaborate to enable input-specific PHP expression.
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