Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines

The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM) activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators.

• Publication year

  2016

• Venue

  PLoS Comput. Biol.

• Publication date

  2016-05-01

• Fields of study

  Biology, Medicine, Computer Science

• Identifiers
  DOI 10.1371/journal.pcbi.1004949PMID 27232631PMCID 4883788
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2015cited by this paper
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• Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates.

  2013cited by this paper
• SK channel modulation rescues striatal plasticity and control over habit in cannabinoid tolerance

  2012cited by this paper
• Calcium signaling in dendritic spines.

  2012cited by this paper
• The spike-timing dependence of plasticity.

  2012cited by this paper
• Spike-Timing-Dependent Plasticity: A Comprehensive Overview

  2012cited by this paper
• Quantitative Regional and Ultrastructural Localization of the Cav2.3 Subunit of R-type Calcium Channel in Mouse Brain

  2012cited by this paper
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  2012cited by this paper
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  2011cited by this paper
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  2011cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2010cited by this paper
• Differential distribution of endoplasmic reticulum controls metabotropic signaling and plasticity at hippocampal synapses

  2009cited by this paper
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  2009cited by this paper
• Membrane Potential Changes in Dendritic Spines during Action Potentials and Synaptic Input

  2009cited by this paper
• Calmodulin Activation by Calcium Transients in the Postsynaptic Density of Dendritic Spines

  2008cited by this paper
• SK2 channel plasticity contributes to LTP at Schaffer collateral–CA1 synapses

  2008cited by this paper
• The development of synaptic plasticity induction rules and the requirement for postsynaptic spikes in rat hippocampal CA1 pyramidal neurones

  2007cited by this paper
• Neurogranin controls the spatiotemporal pattern of postsynaptic Ca2+/CaM signaling.

  2007cited by this paper
• Nonlinear regulation of unitary synaptic signals by CaV(2.3) voltage-sensitive calcium channels located in dendritic spines.

  2007cited by this paper
• Spine Ca2+ Signaling in Spike-Timing-Dependent Plasticity

  2006cited by this paper
• The role of calmodulin as a signal integrator for synaptic plasticity

  2005cited by this paper
• Local signaling with molecular diffusion as a decoder of Ca2+ signals in synaptic plasticity

  2005cited by this paper
• SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala

  2005cited by this paper
• SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines

  2005cited by this paper
• Spike timing-dependent plasticity of neural circuits.

  2004cited by this paper
• Spike Timing-Dependent Plasticity of Neural Circuits

  2004cited by this paper
• The Life Cycle of Ca 2 Ions in Dendritic Spines and

  2002cited by this paper
• A unified model of NMDA receptor-dependent bidirectional synaptic plasticity

  2002cited by this paper
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  2002cited by this paper
• Properties of voltage-gated Ca(2+) channels in rabbit ventricular myocytes expressing Ca(2+) channel alpha(1E) cDNA.

  2001cited by this paper
• Properties of voltage-gated Ca2+ channels in rabbit ventricular myocytes expressing Ca2+ channel α1E cDNA

  2001cited by this paper
• Analysis of calcium channels in single spines using optical fluctuation analysis

  2000cited by this paper
• Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines.

  1999cited by this paper
• Rapid report: postsynaptic bursting is essential for 'Hebbian' induction of associative long-term potentiation at excitatory synapses in rat hippocampus.

  1999cited by this paper
• Mechanisms of Calcium Influx into Hippocampal Spines: Heterogeneity among Spines, Coincidence Detection by NMDA Receptors, and Optical Quantal Analysis

  1999cited by this paper
• Mechanism of calcium gating in small-conductance calcium-activated potassium channels

  1998influential reference
• Usefulness and limitations of linear approximations to the understanding of Ca++ signals.

  1998cited by this paper
• Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons

  1998cited by this paper
• Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs

  1997cited by this paper
• Linearized Buffered Ca2+ Diffusion in Microdomains and Its Implications for Calculation of [Ca2+] at the Mouth of a Calcium Channel

  1997cited by this paper
• A Synaptically Controlled, Associative Signal for Hebbian Plasticity in Hippocampal Neurons

  1997cited by this paper
• Localization of calcium signals by a mobile calcium buffer in frog saccular hair cells

  1994cited by this paper
• An Efficient Method for Computing Synaptic Conductances Based on a Kinetic Model of Receptor Binding

  1994cited by this paper
• Calcium binding to calmodulin and its globular domains.

  1991cited by this paper
• A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory.

  1989cited by this paper
• An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation

  1989cited by this paper
• The journal of neuroscience : the official journal of the Society for Neuroscience.

  1981cited by this paper

• GluN2A- and GluN2B-containing pre-synaptic N-methyl-d-aspartate receptors differentially regulate action potential-evoked Ca2+ influx via modulation of SK channels

  2024cites this paper
• Nano-organization of synaptic calcium signaling

  2024cites this paper
• Making time and space for calcium control of neuron activity.

  2023cites this paper
• NMDA receptors – regulatory function and pathophysiological significance for pancreatic beta cells

  2023cites this paper
• Dendritic spine morphology regulates calcium-dependent synaptic weight change

  2022cites this paper
• Periodicity Pitch Perception Part III: Sensibility and Pachinko Volatility

  2022cites this paper
• A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics

  2022cites this paper
• Attenuation of the extracellular matrix increases the number of synapses but suppresses synaptic plasticity through upregulation of SK channels.

  2021cites this paper
• Direct brain recordings reveal continuous encoding of structure in random stimuli

  2021cites this paper
• Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation.

  2021cites this paper
• Spectral graph theory of brain oscillations—-Revisited and improved

  2021cites this paper
• Improved Characterization of Balancing Selection Genome Wide and a Detailed Look at HLA Genes

  2021cites this paper
• Introducing Undergraduates to Primary Research Literature

  2021cites this paper
• Homeostatic regulation of presynaptic NMDA receptor subunit composition modulates action potential driven Ca2+ influx into boutons setting the bandwidth for information transfer

  2021cites this paper
• Stochastic simulations reveal that dendritic spine morphology regulates synaptic plasticity in a deterministic manner

  2021cites this paper
• Attenuation of the extracellular matrix increases the number of synapses but suppresses synaptic plasticity

  2020cites this paper
• Metabotropic modulation of potassium channels during synaptic plasticity.

  2020cites this paper
• A Purkinje cell model that simulates complex spikes

  2020cites this paper
• APOE4 Affects Basal and NMDAR-Mediated Protein Synthesis in Neurons by Perturbing Calcium Homeostasis

  2020cites this paper
• Stationary Ca2+ nanodomains in the presence of buffers with two binding sites

  2020cites this paper
• Influence of Inter- and Intra-Synaptic Factors on Information Processing in the Brain

  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
• Extension of Rapid Buffering Approximation to Ca2+ Buffers with Two Binding Sites.

  2018cites this paper
• Data-driven computational modelling for some of the implications of dopamine in the brain : From subcellular signalling to area networks

  2018cites this paper
• Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium

  2018cites this paper
• Convergent Metabotropic Signaling Pathways Inhibit SK Channels to Promote Synaptic Plasticity in the Hippocampus

  2018cites this paper
• Modulation of Spike-Timing Dependent Plasticity: Towards the Inclusion of a Third Factor in Computational Models

  2018cites this paper
• A Putative Mechanism of Age-Related Synaptic Dysfunction Based on the Impact of IGF-1 Receptor Signaling on Synaptic CaMKIIα Phosphorylation

  2018cites this paper
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  2017cites this paper
• SK channel subtypes enable parallel optimized coding of behaviorally relevant stimulus attributes: A review

  2017cites this paper
• Mitochondrial dysfunction in oxidative stress

  2017cites this paper
• Spike Frequency Adaptation in Neurons of the Central Nervous System

  2017cites this paper
• Small conductance Ca2+-activated K+ channels in the plasma membrane, mitochondria and the ER: Pharmacology and implications in neuronal diseases.

  2017cites this paper
• Neuromodulation of the Feedforward Dentate Gyrus-CA3 Microcircuit

  2016influential citation
• Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles

  2016cites this paper