Evidence map›Paper›PMID 41325349›Full record

ArticlePLoS biology2025

Glia-to-glia serotonin signaling directs MMP-dependent infiltration for experience-dependent synapse pruning.

Vanessa Kay Miller, Kendal Broadie

Abstract read
In one paragraph

Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors.

Vanessa Kay MillerDepartment of Biological Sciences, Vanderbilt University and Medical Center, Nashville, Tennessee United States of America.
Kendal BroadieDepartment of Biological Sciences, Vanderbilt University and Medical Center, Nashville, Tennessee United States of America.ORCID 0000-0003-3783-6023

Funding

Overall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey L Neul · 2020 to 2026
$10.3M
Glial roles in experience-dependent critical period remodelingR01NS132867 · NINDS · VANDERBILT UNIVERSITY · PI Kendal Broadie · 2024 to 2026
$1.2M
NICHD NIH HHS P50 HD103537NINDS NIH HHS R01 NS132867
6 · The paper itself

Abstract

Synapse connectivity is optimized in response to environmental input in critical periods, characterized by experience-dependent, temporally-restricted, and transiently-reversible synapse pruning by glial phagocytes. This precise, targeted synaptic elimination process requires glial serotonergic intercellular signaling. We discover glia-to-glia communication between different glial classes is essential for experience-dependent synaptic pruning in a well-defined Drosophila juvenile brain olfactory critical period. We find ensheathing glia infiltrate specific target synaptic glomeruli in response to guiding odorant experience via 5-HT2A receptor (5-HT2AR) signaling. Using cell-targeted tryptophan hydroxylase (Trhn) RNAi to block serotonin production, we discover serotonin signaling from ensheathing glia is required for experience-dependent synapse pruning. Using cell-targeted 5-HT2AR RNAi, we find the serotonin receptor is required exclusively in astrocyte-like glia (ALG). Using cell-targeted 5-HT2AR rescue in 5-HT2AR null mutants, we discover the serotonin receptor mediates experience-dependent synapse pruning. Thus, glia-to-glia serotonin signaling between different glial classes mediated by 5-HT2A receptors is necessary and sufficient for synapse elimination. We discover that ALG-targeted conditional 5-HT2AR in mature adults induces experience-dependent synapse pruning indistinguishable from the critical period mechanism. Thus, astrocyte 5-HT2AR signaling is sufficient to 're-open' this characteristic critical period remodeling capability at maturity. We find astrocytic matrix metalloproteinase-1 (MMP-1) induced by critical period odorant experience is required for experience-dependent synapse pruning downstream of 5HT2AR activation. We discover that ALG-targeted MMP-1 induction restores synapse pruning in the absence of 5HT2AR signaling. Taken together, we conclude that glia-to-glia serotonergic 5HT2AR signaling drives MMP-1 for experience-dependent infiltration phagocytosis synapse pruning, and can rekindle this remodeling capacity at adult maturity.

Indexed as

Matrix MetalloproteinasesNeurogliaNeuronal PlasticitySerotoninSynapsesAnimalsAstrocytesDrosophila melanogasterDrosophila ProteinsReceptor, Serotonin, 5-HT2ASignal TransductionTryptophan HydroxylaseDrosophila ProteinsMatrix MetalloproteinasesReceptor, Serotonin, 5-HT2ASerotoninTryptophan Hydroxylase

Identifiers

PMID41325349
PMCPMC12668486

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.