title: Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus.
abstract: The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9 rue du Bugnon, 1005, Lausanne, Switzerland.
authors.forename: Marine
authors.initials: M
authors.lastname: Krzisch
authors.forename: Silvio G
authors.initials: SG
authors.lastname: Temprana
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Mongiat
authors.forename: Jan
authors.initials: J
authors.lastname: Armida
authors.forename: Valentin
authors.initials: V
authors.lastname: Schmutz
authors.forename: Mari A
authors.initials: MA
authors.lastname: Virtanen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kocher-Braissant
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kraftsik
authors.forename: Laszlo
authors.initials: L
authors.lastname: Vutskits
authors.forename: Karl-Klaus
authors.initials: KK
authors.lastname: Conzelmann
authors.forename: Matteo
authors.initials: M
authors.lastname: Bergami
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: Schinder
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000648:ultrastructure; D001973:Bromodeoxyuridine / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D064568:S100 Calcium Binding Protein beta Subunit; D049452:Green Fluorescent Proteins; C020889:dihydrokainic acid; D000080924:Aldehyde Dehydrogenase 1 Family; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; D007608:Kainic Acid
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