Ryanodine Receptor Activation Induces Long-Term Plasticity of Spine Calcium Dynamics

A key feature of signalling in dendritic spines is the synapse-specific transduction of short electrical signals into biochemical responses. Ca(2+) 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) Ca(2+) transients. These transients translate neuronal suprathreshold activation into intracellular biochemical events. Using a combination of electrophysiology, two-photon Ca(2+) imaging, and modelling, we demonstrate that bAPs are electrochemically coupled to Ca(2+) 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-Ca(2+) transient. Spines regulate bAP Ca(2+) influx independent of each other, as bAP-Ca(2+) transient enhancement is compartmentalized and independent of the dendritic Ca(2+) transient. Furthermore, this functional state change depends exclusively on bAPs travelling antidromically into dendrites and spines. Induction, but not expression, of bAP-Ca(2+) transient enhancement is a spine-specific function of the RyR. We demonstrate that RyRs can form specific Ca(2+) signalling nanodomains within single spines. Functionally, RyR mediated Ca(2+) release in these nanodomains induces a new form of Ca(2+) transient plasticity that constitutes a spine specific storage mechanism of neuronal suprathreshold activity patterns.