title: Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening.
abstract: Refinement of neural circuits in the mammalian cerebral cortex shapes brain function during development and in the adult. However, the signaling mechanisms underlying the synapse-specific shrinkage and loss of spiny synapses when neural circuits are remodeled remain poorly defined. Here, we show that low-frequency glutamatergic activity at individual dendritic spines leads to synapse-specific synaptic weakening and spine shrinkage on CA1 neurons in the hippocampus. We found that shrinkage of individual spines in response to low-frequency glutamate uncaging is saturable, reversible, and requires NMDA receptor activation. Notably, shrinkage of large spines additionally requires signaling through metabotropic glutamate receptors (mGluRs) and inositol 1,4,5-trisphosphate receptors (IP(3)Rs), supported by higher levels of mGluR signaling activity in large spines. Our results support a model in which signaling through both NMDA receptors and mGluRs is required to drive activity-dependent synaptic weakening and spine shrinkage at large, mature dendritic spines when neural circuits undergo experience-dependent modification.
authors.affiliation: Center for Neuroscience, University of California, Davis, CA 95616, USA.
authors.forename: Won Chan
authors.initials: WC
authors.lastname: Oh
authors.forename: Travis C
authors.initials: TC
authors.lastname: Hill
authors.forename: Karen
authors.initials: K
authors.lastname: Zito
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004558:Electric Stimulation; D005971:Glutamates / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D036641:Microscopy, Fluorescence, Multiphoton; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D014162:Transfection
chemical_list: C440256:4-methoxy-7-nitroindolinyl-glutamate; D005971:Glutamates; D007211:Indoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins