Axonal RNA localization is essential for long-term memory
Localization of mRNAs to neuronal terminals, coupled to local translation, has emerged as a prevalent mechanism controlling the synaptic proteome. However, the physiological regulation and function of this process in the context of mature in vivo memory circuits has remained unclear. Here, we combined synaptosome RNA profiling with whole brain high-resolution imaging to uncover mRNAs with different localization patterns in the axons of Drosophila Mushroom Body memory neurons, some exhibiting regionalized, input-dependent, recruitment along axons. By integrating transcriptome-wide binding approaches and functional assays, we show that the conserved Imp RNA binding protein controls the transport of mRNAs to Mushroom Body axons and characterize a mutant in which this transport is selectively impaired. Using this unique mutant, we demonstrate that axonal mRNA localization is required for long-term, but not short-term, behavioral memory. This work uncovers circuit-dependent mRNA targeting in vivo and demonstrates the importance of local RNA regulation in memory consolidation.
Authors
- Bruna R. de Queiroz (ORCID: https://orcid.org/0009-0000-1469-4275)
- Fabienne De Graeve (ORCID: https://orcid.org/0000-0002-3455-7507)
- Mirana Ramialison (ORCID: https://orcid.org/0000-0001-6315-4777)
- S. Rajeev (ORCID: https://orcid.org/0009-0005-9291-6933)
- Arnaud Hubstenberger (ORCID: https://orcid.org/0000-0001-8532-3578)
- Chantal Cazevieille (ORCID: https://orcid.org/0000-0003-4113-1309)
- Martina Hallegger (ORCID: https://orcid.org/0000-0002-5126-5346)
- Marion Dunoyer de Segonzac (ORCID: https://orcid.org/0009-0002-3994-8424)
- Krystyna Keleman (ORCID: https://orcid.org/0000-0003-2044-1981)
- Florence Besse (ORCID: https://orcid.org/0000-0003-4672-1068)
- Marine Dehecq
- Ugur Dag (ORCID: https://orcid.org/0000-0001-6937-5722)
- Hiba Laghrissi
- L. Blot
- Jernej Ule (ORCID: https://orcid.org/0000-0002-2452-4277)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Royal Children's Hospital (AU)
- Centre for Human Genetics (GB)
- Howard Hughes Medical Institute (US)
- Inserm (FR)
- The University of Melbourne (AU)
- King's College London (GB)
- Janelia Research Campus (US)
- Université de Montpellier (FR)
- Université Côte d'Azur (FR)
- The Francis Crick Institute (GB)
- Australian Regenerative Medicine Institute (AU)
- University of Oxford (GB)
- Institut de Biologie Valrose (FR)
- UK Dementia Research Institute (GB)
- Murdoch Children's Research Institute (AU)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-15
- DOI
- https://doi.org/10.1038/s41467-025-57651-7
- Citations
- 12
- Primary Topic
- Neurobiology and Insect Physiology Research
- Type
- article
- Field-Weighted Citation Impact
- 9.09
Funders
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale