Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes

Sébastien Sultan; Liyi Li; Jonathan Moss; Francesco Petrelli; Frédéric Cassé; Elias Gebara; Jan Lopatar; Frank W Pfrieger; Paola Bezzi; Josef Bischofberger; Nicolas Toni

doi:10.1016/j.neuron.2015.10.037

Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes

Neuron. 2015 Dec 2;88(5):957-972. doi: 10.1016/j.neuron.2015.10.037. Epub 2015 Nov 19.

Authors

Affiliations

¹ University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
² Department of Biomedicine, Physiological Institute, University of Basel, Pestalozzistrasse 20, 4056 Basel, Switzerland.
³ CNRS UPR 3212, University of Strasbourg, Institute of Cellular and Integrative Neurosciences, 67084 Strasbourg, France.
⁴ University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland. Electronic address: nicolas.toni@unil.ch.

PMID: 26606999
DOI: 10.1016/j.neuron.2015.10.037

Abstract

Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons.

Publication types

Research Support, Non-U.S. Gov't
Video-Audio Media

MeSH terms

Animals
Astrocytes / physiology*
Astrocytes / ultrastructure
Clostridium botulinum type B / genetics
Clostridium botulinum type B / metabolism
Dendritic Spines / physiology
Dendritic Spines / ultrastructure
Excitatory Amino Acid Transporter 1 / metabolism
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / genetics
Glial Fibrillary Acidic Protein / genetics
Glial Fibrillary Acidic Protein / metabolism
Hippocampus / cytology*
Membrane Potentials / drug effects
Membrane Potentials / physiology
Mice
Mice, Transgenic
Neurogenesis / genetics
Neurogenesis / physiology*
Neurons / physiology*
Neurons / ultrastructure
Phosphopyruvate Hydratase / metabolism
Receptors, N-Methyl-D-Aspartate / genetics
Receptors, N-Methyl-D-Aspartate / metabolism
SNARE Proteins / genetics
SNARE Proteins / metabolism
Serine / pharmacology
Sodium Chloride / pharmacology
Synapses / genetics
Synapses / physiology*
Synapses / ultrastructure
Synaptic Transmission / drug effects
Synaptic Transmission / genetics
Tamoxifen / pharmacology

Substances

Excitatory Amino Acid Transporter 1
Glial Fibrillary Acidic Protein
Receptors, N-Methyl-D-Aspartate
SNARE Proteins
Slc1a3 protein, mouse
Tamoxifen
Sodium Chloride
Serine
Phosphopyruvate Hydratase