Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells

Carles Bosch; Nuria Masachs; David Exposito-Alonso; Albert Martínez; Cátia M Teixeira; Isabel Fernaud; Lluís Pujadas; Fausto Ulloa; Joan X Comella; Javier DeFelipe; Angel Merchán-Pérez; Eduardo Soriano

doi:10.1093/cercor/bhw216

Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells

Cereb Cortex. 2016 Oct 17;26(11):4282-4298. doi: 10.1093/cercor/bhw216.

Authors

Carles Bosch^{1

2

3}, Nuria Masachs^{1

2}, David Exposito-Alonso¹, Albert Martínez¹, Cátia M Teixeira^{1

2}, Isabel Fernaud^{2

4

5}, Lluís Pujadas^{1

2

3}, Fausto Ulloa^{1

2}, Joan X Comella^{2

3

6}, Javier DeFelipe^{2

4

5}, Angel Merchán-Pérez^{2

4

7}, Eduardo Soriano^{1

2

3

8}

Affiliations

¹ Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.
² Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.
³ Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), Barcelona 08023, Spain.
⁴ Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Madrid 28223, Spain.
⁵ Instituto Cajal (Consejo Superior de Investigaciones Científicas), Madrid 28002, Spain.
⁶ Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain.
⁷ Departamento de Arquitectura y Tecnología de Sistemas Informáticos, Escuela Técnica Superior de Ingenieros Informáticos, Universidad Politécnica de Madrid, Madrid 28660, Spain.
⁸ Institució Catalana de Recerca i Estudis Avançats Academia, Barcelona 08010, Spain.

Abstract

The extracellular protein Reelin has an important role in neurological diseases, including epilepsy, Alzheimer's disease and psychiatric diseases, targeting hippocampal circuits. Here we address the role of Reelin in the development of synaptic contacts in adult-generated granule cells (GCs), a neuronal population that is crucial for learning and memory and implicated in neurological and psychiatric diseases. We found that the Reelin pathway controls the shapes, sizes, and types of dendritic spines, the complexity of multisynaptic innervations and the degree of the perisynaptic astroglial ensheathment that controls synaptic homeostasis. These findings show a pivotal role of Reelin in GC synaptogenesis and provide a foundation for structural circuit alterations caused by Reelin deregulation that may occur in neurological and psychiatric disorders.

Keywords: 3D-electron microscopy; FIB/SEM; adult neurogenesis; axospinous synapses; glia.

MeSH terms

Animals
Brain / cytology*
Cell Adhesion Molecules, Neuronal / genetics
Cell Adhesion Molecules, Neuronal / metabolism*
Cell Differentiation
Dendritic Spines / metabolism*
Dendritic Spines / ultrastructure
Disks Large Homolog 4 Protein / metabolism
Extracellular Matrix Proteins / genetics
Extracellular Matrix Proteins / metabolism*
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Imaging, Three-Dimensional
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Mutation / genetics
Nerve Tissue Proteins / deficiency
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neurogenesis / physiology*
Neuroglia / physiology*
Neurons / physiology*
Reelin Protein
Serine Endopeptidases / genetics
Serine Endopeptidases / metabolism*
Signal Transduction / physiology
Synapses / physiology*
Synapses / ultrastructure
Transduction, Genetic

Substances

Cell Adhesion Molecules, Neuronal
Dab1 protein, mouse
Disks Large Homolog 4 Protein
Dlg4 protein, mouse
Extracellular Matrix Proteins
Nerve Tissue Proteins
Reelin Protein
Green Fluorescent Proteins
Reln protein, mouse
Serine Endopeptidases