title: Heterosynaptic structural plasticity on local dendritic segments of hippocampal CA1 neurons.
abstract: Competition between synapses contributes to activity-dependent refinement of the nervous system during development. Does local competition between neighboring synapses drive circuit remodeling during experience-dependent plasticity in the cerebral cortex? Here, we examined the role of activity-mediated competitive interactions in regulating dendritic spine structure and function on hippocampal CA1 neurons. We found that high-frequency glutamatergic stimulation at individual spines, which leads to input-specific synaptic potentiation, induces shrinkage and weakening of nearby unstimulated synapses. This heterosynaptic plasticity requires potentiation of multiple neighboring spines, suggesting that a local threshold of neural activity exists beyond which inactive synapses are punished. Notably, inhibition of calcineurin, IP3Rs, or group I metabotropic glutamate receptors (mGluRs) blocked heterosynaptic shrinkage without blocking structural potentiation, and inhibition of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) blocked structural potentiation without blocking heterosynaptic shrinkage. Our results support a model in which activity-induced shrinkage signal, and not competition for limited structural resources, drives heterosynaptic structural and functional depression during neural circuit refinement.
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, CA 95616, USA.
authors.forename: Won Chan
authors.initials: WC
authors.lastname: Oh
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, CA 95616, USA.
authors.forename: Laxmi Kumar
authors.initials: LK
authors.lastname: Parajuli
authors.affiliation: Center for Neuroscience, University of California Davis, Davis, CA 95616, USA. Electronic address: kzito@ucdavis.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Zito
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D019703:Calcineurin / Q000737:chemistry / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D003712:Dendrites / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D018094:Receptors, Metabotropic Glutamate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin