Adult inactivation of the Reln gene leads to disruption of cortical lamination and rhythmic activity
Yasmina Manso, Nuria Masachs, Alba Vílchez-Acosta, Victoria González, Gerardo Contreras-Murillo, Raudel Sánchez-Campusano, Marc Hernaiz-Llorens, Alba Elias-Tersa, María Ángeles Llanos, Gerard Rovira-Escalé, Ana Guerrero, Magdalena Martínez-Losa, Manuel Álvarez-Dolado, José María Delgado-García, Angus C Nairn, Agnès Gruart, Eduardo SorianoAbstract
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.