GSK-3β Orchestrates the Inhibitory Innervation of Adult-born Dentate Granule Cells in Vivo

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2023 Jul 23

PMID 37481766

Authors

E P Moreno-Jimenez

M Flor-Garcia

A Hernandez-Vivanco

J Terreros-Roncal

C B Rodriguez-Moreno

N Toni

P Mendez

Maria Llorens-Martin

Affiliations

Soon will be listed here.

Abstract

Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3β) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3β-overexpressing newborn neurons show an increased number and altered size of Gephyrin postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3β overexpression triggers a depletion of Parvalbumin interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3β is dysregulated.

Citing Articles

Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review.

Cui C, Jiang X, Wang Y, Li C, Lin Z, Wei Y Cell Mol Neurobiol. 2024; 44(1):58.

PMID: 39105862 PMC: 11303443. DOI: 10.1007/s10571-024-01491-4.

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