title: Nonlinear [Ca2+] signaling in dendrites and spines caused by activity-dependent depression of Ca2+ extrusion.
abstract: Spine Ca2+ triggers the induction of synaptic plasticity and other adaptive neuronal responses. The amplitude and time course of Ca2+ signals specify the activation of the signaling pathways that trigger different forms of plasticity such as long-term potentiation and depression. The shapes of Ca2+ signals are determined by the dynamics of Ca2+ sources, Ca2+ buffers, and Ca2+ extrusion mechanisms. Here we show in rat CA1 pyramidal neurons that plasma membrane Ca2+ pumps (PMCAs) and Na+/Ca2+ exchangers are the major Ca2+ extrusion pathways in spines and small dendrites. Surprisingly, we found that Ca2+ extrusion via PMCA and Na+/Ca2+ exchangers slows in an activity-dependent manner, mediated by intracellular Na+ and Ca2+ accumulations. This activity-dependent depression of Ca2+ extrusion is, in part, attributable to Ca2+-dependent inactivation of PMCAs. Ca2+ extrusion recovers from depression with a time constant of 0.5 s. Depression of Ca2+ extrusion provides a positive feedback loop, converting small differences in stimuli into large differences in Ca2+ concentration. Depression of Ca2+ extrusion produces Ca2+ concentration dynamics that depend on the history of neuronal activity and therefore likely modulates the induction of synaptic plasticity.
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Volker
authors.initials: V
authors.lastname: Scheuss
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yasuda
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sobczyk
authors.forename: Karel
authors.initials: K
authors.lastname: Svoboda
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology; D007700:Kinetics; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D019831:Sodium-Calcium Exchanger; D002118:Calcium