Control of synapse number by glia.
Although astrocytes constitute nearly half of the cells in our brain, their function is a long-standing neurobiological mystery. Here we show by quantal analyses, FM1-43 imaging, immunostaining, and electron microscopy that few synapses form in the absence of glial cells and that the few synapses that do form are functionally immature. Astrocytes increase the number of mature, functional synapses on central nervous system (CNS) neurons by sevenfold and are required for synaptic maintenance in vitro. We also show that most synapses are generated concurrently with the development of glia in vivo. These data demonstrate a previously unknown function for glia in inducing and stabilizing CNS synapses, show that CNS synapse number can be profoundly regulated by nonneuronal signals, and raise the possibility that glia may actively participate in synaptic plasticity.
Ullian
E M
EM
Stanford University School of Medicine, Department of Neurobiology, Fairchild Science Building, Stanford, CA 94305-5125, USA. emu@stanford.edu
Sapperstein
S K
SK
Christopherson
K S
KS
Barres
B A
BA
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D019706:Excitatory Postsynaptic Potentials; D005456:Fluorescent Dyes / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology* / Q000648:ultrastructure; D013477:Superior Colliculi / Q000196:embryology / Q000254:growth & development / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; C073804:FM1 43; D005456:Fluorescent Dyes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; C489618:Sv2a protein, rat; D016708:Synaptophysin; D050857:Synaptotagmins; D018698:Glutamic Acid; D015759:Ionomycin; D002118:Calcium