title: Glial glutamate transport modulates dendritic spine head protrusions in the hippocampus.
abstract: Accumulating evidence supports the idea that synapses are tripartite, whereby perisynaptic astrocytes modulate both pre- and postsynaptic function. Although some of these features have been uncovered by using electrophysiological methods, less is known about the structural interplay between synapses and glial processes. Here, we investigated how astrocytes govern the plasticity of individual hippocampal dendritic spines. Recently, we uncovered that a subgroup of innervated dendritic spines is able to undergo remodeling by extending spine head protrusions (SHPs) toward neighboring functional presynaptic boutons, resulting in new synapses. Although glutamate serves as a trigger, how this behavior is regulated is unknown. As astrocytes control extracellular glutamate levels through their high-affinity uptake transporters, together with their privileged access to synapses, we investigated a role for astrocytes in SHP formation. Using time-lapse confocal microscopy, we found that the volume overlap between spines and astrocytic processes decreased during the formation of SHPs. Focal application of glutamate also reduced spine-astrocyte overlap and induced SHPs. Importantly, SHP formation was prevented by blocking glial glutamate transporters, suggesting that glial control of extracellular glutamate is important for SHP-mediated plasticity of spines. Hence, the dynamic changes of both spines and astrocytes can rapidly modify synaptic connectivity.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montréal, QC H3G 0B1, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Verbich
authors.forename: George A
authors.initials: GA
authors.lastname: Prenosil
authors.forename: Philip K-Y
authors.initials: PK
authors.lastname: Chang
authors.forename: Keith K
authors.initials: KK
authors.lastname: Murai
authors.forename: R Anne
authors.initials: RA
authors.lastname: McKinney
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D027322:Amino Acid Transport System X-AG; D018698:Glutamic Acid