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Activation of feedforward wiring in adult hippocampal neurons by the basic-helix-loop-helix transcription factor Ascl4


Luo, Wenshu; Egger, Matteo; Cruz-Ochoa, Natalia; Tse, Alice; Maloveczky, Gyula; Tamás, Bálint; Lukacsovich, David; Seng, Charlotte; Amrein, Irmgard; Lukacsovich, Tamás; Wolfer, David; Földy, Csaba (2024). Activation of feedforward wiring in adult hippocampal neurons by the basic-helix-loop-helix transcription factor Ascl4. PNAS Nexus, 3(5):pgae174.

Abstract

Although evidence indicates that the adult brain retains a considerable capacity for circuit formation, adult wiring has not been broadly considered and remains poorly understood. In this study, we investigate wiring activation in adult neurons. We show that the basic-helix-loop-helix transcription factor Ascl4 can induce wiring in different types of hippocampal neurons of adult mice. The new axons are mainly feedforward and reconfigure synaptic weights in the circuit. Mice with the Ascl4-induced circuits do not display signs of pathology and solve spatial problems equally well as controls. Our results demonstrate reprogrammed connectivity by a single transcriptional factor and provide insights into the regulation of brain wiring in adults.

Abstract

Although evidence indicates that the adult brain retains a considerable capacity for circuit formation, adult wiring has not been broadly considered and remains poorly understood. In this study, we investigate wiring activation in adult neurons. We show that the basic-helix-loop-helix transcription factor Ascl4 can induce wiring in different types of hippocampal neurons of adult mice. The new axons are mainly feedforward and reconfigure synaptic weights in the circuit. Mice with the Ascl4-induced circuits do not display signs of pathology and solve spatial problems equally well as controls. Our results demonstrate reprogrammed connectivity by a single transcriptional factor and provide insights into the regulation of brain wiring in adults.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > Brain Research Institute
08 Research Priority Programs > Adaptive Brain Circuits in Development and Learning (AdaBD)
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Multidisciplinary
Language:English
Date:3 May 2024
Deposited On:05 Jun 2024 08:43
Last Modified:07 Jun 2024 08:06
Publisher:Oxford University Press
ISSN:2752-6542
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/pnasnexus/pgae174
PubMed ID:38711810
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)