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Record W4283787382 · doi:10.1101/2022.06.27.497827

Local axonal translation sustains synapse-type-specific neurotransmission

2022· preprint· en· W4283787382 on OpenAlexafffund
Hovy Ho‐Wai Wong, Alanna J. Watt, P. Jesper Sjöström

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsMcGill UniversityMcGill University Health CentreMontreal General Hospital
FundersFonds de Recherche du Québec - SantéNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsNeuroscienceNeurotransmissionPostsynaptic potentialSynapseBiologySynaptic plasticityAxonTranslation (biology)Pyramidal cellHippocampal formationCell biologyReceptor

Abstract

fetched live from OpenAlex

Abstract Dendritic protein synthesis is a well-known regulator of neurotransmission in the central nervous system. For example, local on-demand protein synthesis in dendrites is required for hippocampal long-term 1,2 and homeostatic plasticity 3 . Although axonal protein synthesis is a key regulator in neural circuit assembly during early development 4–6 , it is unclear if local translation in mature axons plays a functional role in neurotransmission of the mammalian central nervous system. Here we show that local translation in axons regulates pyramidal cell neurotransmission in primary visual cortex microcircuits in a synapse-type-specific manner 7,8 . Using paired recordings to manipulate pre- and postsynaptic neurons independently, we found that presynaptic translation sustains neurotransmission and regulates short-term plasticity. This was mediated via mTOR and cap-dependent translation, with presynaptic NMDA receptors acting as an up-stream trigger. By isolating the axon from the soma with laser microsurgery, we unveiled that axonal translation was required to sustain neurotransmission. With live endogenous RNA imaging, we found that RNA granules stably docked in individual presynaptic compartments, suggesting bouton-specific regulation. In agreement, presynaptic translation influenced pyramidal cell synapses to neighbouring pyramidal cells, but not to inhibitory Martinotti cells. Our study establishes local protein synthesis in mature axons as a fundamental regulatory principle that governs information transfer at central synapses.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.060
GPT teacher head0.298
Teacher spread0.237 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicNeuroscience and Neuropharmacology Research→French-language works237,207→