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.
Highlights
A fundamental principle in neuronal signal processing is the transduction of short electrical signals at the membrane into biochemical responses, resulting in longer lasting changes of the neuronal structural and functional state
Using a combination of electrophysiology, two-photon Ca2+ imaging, and modelling, we demonstrate that back-propagating action potential (bAP) 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
Summary
A fundamental principle in neuronal signal processing is the transduction of short electrical signals at the membrane into biochemical responses, resulting in longer lasting changes of the neuronal structural and functional state. Ca2+ molecules have a key role in this transfer process; they transduce electrical signals at the membrane into second messenger pathways involved in a number of adaptive responses. These include changes in synaptic strength, membrane excitability, cell morphology, and gene expression [1]. Spines serve as independent biochemical and electrical functional units that provide synapse specific Ca2+ signals [4]. This compartmentalization results in the transduction of neuronal activity into a spine-specific Ca2+ code. It is important to understand the regulation and dynamics of spine Ca2+ signalling
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