title: Ryanodine Receptor Activation Induces Long-Term Plasticity of Spine Calcium Dynamics.
abstract: A key feature of signalling in dendritic spines is the synapse-specific transduction of short electrical signals into biochemical responses. Ca2+ is a major upstream effector in this transduction cascade, serving both as a depolarising electrical charge carrier at the membrane and an intracellular second messenger. Upon action potential firing, the majority of spines are subject to global back-propagating action potential (bAP) Ca2+ transients. These transients translate neuronal suprathreshold activation into intracellular biochemical events. Using a combination of electrophysiology, two-photon Ca2+ imaging, and modelling, we demonstrate that bAPs are electrochemically coupled to Ca2+ release from intracellular stores via ryanodine receptors (RyRs). We describe a new function mediated by spine RyRs: the activity-dependent long-term enhancement of the bAP-Ca2+ transient. Spines regulate bAP Ca2+ influx independent of each other, as bAP-Ca2+ transient enhancement is compartmentalized and independent of the dendritic Ca2+ transient. Furthermore, this functional state change depends exclusively on bAPs travelling antidromically into dendrites and spines. Induction, but not expression, of bAP-Ca2+ transient enhancement is a spine-specific function of the RyR. We demonstrate that RyRs can form specific Ca2+ signalling nanodomains within single spines. Functionally, RyR mediated Ca2+ release in these nanodomains induces a new form of Ca2+ transient plasticity that constitutes a spine specific storage mechanism of neuronal suprathreshold activity patterns.
authors.affiliation: Neuroscience Research Center, Charité-Universitätsmedizin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Johenning
authors.affiliation: Neuroscience Research Center, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Theis
authors.affiliation: Neuroscience Research Center, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pannasch
authors.affiliation: Institute of Physics, Humboldt Universität, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rückl
authors.affiliation: Institute of Physics, Humboldt Universität, Berlin, Germany.
authors.forename: Sten
authors.initials: S
authors.lastname: Rüdiger
authors.affiliation: Neuroscience Research Center, Charité-Universitätsmedizin, Berlin, Germany; Bernstein Center for Computational Neuroscience, Berlin, Germany; Cluster of Excellence 'NeuroCure', Charité-Universitätsmedizin, Berlin, Germany; DZNE- German Center for Neurodegenerative Diseases, Berlin, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
mesh_terms: D000200:Action Potentials; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D018728:Entorhinal Cortex / Q000378:metabolism; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium