Adult inactivation of the Reln gene leads to disruption of cortical lamination and rhythmic activity
Abstract Cortical cytoarchitecture and lamination are believed to remain stable after completion of development. Here we demonstrate that early postnatal and adult (P45-P60) inactivation of the Reln gene results in dispersion of layer II-III neocortical neurons which invade layer I. In addition, neuronal mispositioning was observed in the dentate gyrus, the CA1-CA3 regions and in the cerebellum. Interestingly, inactivation of the Reln gene at adult stages resulted in altered oscillatory network activity in different cortical regions and in the nucleus accumbens. Moreover, Reelin deficiency increased depression-like behaviour and impaired long-term memory consolidation. Thus, besides its crucial developmental role, Reelin is important in maintaining adult cortical lamination and rhythmic neuronal synchronization. These results suggest that, in addition to physiological and synaptic plasticity, there may be a certain degree of laminar structural plasticity in adult stages, which may lead to reconsidering the origin of layering alterations observed in neuropsychiatric diseases.
Authors
- Yasmina Manso (ORCID: https://orcid.org/0000-0002-5788-4180)
- Núria Masachs
- Marc Hernaiz-Llorens (ORCID: https://orcid.org/0000-0003-1052-9613)
- Jose Maria Delgado-Garcia (ORCID: https://orcid.org/0000-0001-7369-4195)
- Angus Clark Nairn (ORCID: https://orcid.org/0000-0002-7075-0195)
- Alba Elias-Tersa (ORCID: https://orcid.org/0000-0002-6416-1677)
- Alba Vílchez-Acosta (ORCID: https://orcid.org/0000-0001-8268-591X)
- Gerardo Contreras-Murillo (ORCID: https://orcid.org/0000-0001-5712-2760)
- Raudel Sánchez‐Campusano (ORCID: https://orcid.org/0000-0003-3132-2769)
- Manuel Álvarez‐Dolado (ORCID: https://orcid.org/0000-0002-0655-8289)
- Magdalena Martínez‐Losa (ORCID: https://orcid.org/0000-0003-4451-7549)
- Agnès Gruart (ORCID: https://orcid.org/0000-0002-2309-0323)
- Eduardo Soriano (ORCID: https://orcid.org/0000-0001-9260-9291)
- Ana Guerrero
- Victoria González
- María Ángeles Llanos
- Gerard Rovira-Escalé (ORCID: https://orcid.org/0009-0000-8932-8448)
Institutions
- Instituto de Salud Carlos III (ES)
- Yale University (US)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Centro Andaluz de Biología Molecular y Medicina Regenerativa (ES)
- Universitat de Barcelona (ES)
- Universidad Pablo de Olavide (ES)
Publication Details
- Journal
- PNAS Nexus
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1093/pnasnexus/pgag363
- Primary Topic
- Neurogenesis and neuroplasticity mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Junta de Andalucía
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación