Pre-Sensory Spontaneous Activity Accelerates Coordinated Maturation of Synaptic Partners and Drives Transition to the Mature Physiological Phenotype

Daniel T Heller; Nikollas M Benites; Emily M Amick; Andre Dagostin; Samuel M Young; Henrique von Gersdorff; George A Spirou

doi:10.1101/2025.08.28.672917

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Pre-Sensory Spontaneous Activity Accelerates Coordinated Maturation of Synaptic Partners and Drives Transition to the Mature Physiological Phenotype

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Pre-Sensory Spontaneous Activity Accelerates Coordinated Maturation of Synaptic Partners and Drives Transition to the Mature Physiological Phenotype

Daniel T Heller, Nikollas M Benites, Emily M Amick, Andre Dagostin, Samuel M Young, Henrique von Gersdorff and George A Spirou

bioRxiv

Cold Spring Harbor Laboratory

08/28/2025

DOI: 10.1101/2025.08.28.672917

PMCID: PMC12407975

PMID: 40909639

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https://doi.org/10.1101/2025.08.28.672917View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Pre-sensory (ps), peripherally-generated spontaneous activity (SA) is important for establishing basic topography of central components of sensory pathways. However, roles for psSA in sculpting connections at the single neuron level and in driving functional maturation of postsynaptic targets are difficult to isolate and therefore little explored. We capitalized on the temporal onset of cochlea-generated psSA just prior to growth of the calyx of Held (CH), the largest nerve terminal in the mammalian brain, and its well-defined circuit topography to explore the causal roles for psSA in targeted synaptogenesis and postsynaptic functional maturation. To this end, we developed a viral vector to rapidly express tetanus neurotoxin (TeNT), which blocks neurotransmission, and selectively introduced it into CH-forming neurons at the onset of psSA. TeNT expression did not prevent but delayed and altered the developmental trajectory of neural circuit maturation, which in sum prevented the postsynaptic neuron from acquiring its mature phasic firing phenotype. Thus, psSA initiates and drives circuit maturation along central sensory pathways, but alternative mechanisms can partially compensate in its absence.

Details

Title: Subtitle: Pre-Sensory Spontaneous Activity Accelerates Coordinated Maturation of Synaptic Partners and Drives Transition to the Mature Physiological Phenotype
Creators: Daniel T Heller - University of South Florida
Nikollas M Benites - University of South Florida
Emily M Amick - University of South Florida
Andre Dagostin - Oregon Health & Science University
Samuel M Young - University of North Carolina at Chapel Hill
Henrique von Gersdorff - Oregon Health & Science University
George A Spirou - University of South Florida
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2025.08.28.672917
PMID: 40909639
PMCID: PMC12407975
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Language: English
Date posted: 08/28/2025
Academic Unit: Otolaryngology
Record Identifier: 9984958625102771

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