ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
A stochastic signaling network mediates the probabilistic induction of cerebellar long-term depression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 69 citations in OpenAlex.
- Dynamic regulation of vesicle pools in a detailed spatial model of the complete synaptic vesicle cycle.Science advances · 2025Article
- Vesicle and reaction-diffusion hybrid modeling with STEPS.Communications biology · 2024Article
- Purkinje cell models: past, present and future.Frontiers in computational neuroscience · 2024Review
- PDI augments kainic acid-induced seizure activity and neuronal death by inhibiting PP2A-GluA2-PICK1-mediated AMPA receptor internalization in the mouse hippocampus.Scientific reports · 2023Article
- A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics.eLife · 2023Article
- Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway.iScience · 2023Article
- Autoregulation of switching behavior by cellular compartment size.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- STEPS 4.0: Fast and memory-efficient molecular simulations of neurons at the nanoscale.Frontiers in neuroinformatics · 2022Article
- Mechanism underlying hippocampal long-term potentiation and depression based on competition between endocytosis and exocytosis of AMPA receptors.Scientific reports · 2020Article
- Binding of Filamentous Actin to CaMKII as Potential Regulation Mechanism of Bidirectional Synaptic Plasticity by β CaMKII in Cerebellar Purkinje Cells.Scientific reports · 2020Article
- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- From membrane receptors to protein synthesis and actin cytoskeleton: Mechanisms underlying long lasting forms of synaptic plasticity.Seminars in cell & developmental biology · 2019Review
- Intracellular calcium stores mediate metaplasticity at hippocampal dendritic spines.The Journal of physiology · 2019Article
- Postsynaptic Stability and Variability Described by a Stochastic Model of Endosomal Trafficking.Frontiers in cellular neuroscience · 2019Article
- Molecular mechanisms of detection and discrimination of dynamic signals.Scientific reports · 2018Article
- CaFrontiers in molecular neuroscience · 2018Article
- Timely regulated sorting from early to late endosomes is required to maintain cerebellar long-term depression.Nature communications · 2017Article
- β-adrenergic signaling broadly contributes to LTP induction.PLoS computational biology · 2017Article
- Small-Volume Effect Enables Robust, Sensitive, and Efficient Information Transfer in the Spine.Biophysical journal · 2017Article
- A Model of Induction of Cerebellar Long-Term Depression Including RKIP Inactivation of Raf and MEK.Frontiers in molecular neuroscience · 2017Article
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Many cellular processes involve a small number of molecules and undergo stochastic fluctuations in their levels of activity. Cerebellar long-term depression (LTD) is a form of synaptic plasticity expressed as a reduction in the number of synaptic AMPA receptors (AMPARs) in Purkinje cells. We developed a stochastic model of the LTD signaling network, including a PKC-ERK-cPLA(2) positive feedback loop and mechanisms of AMPAR trafficking, and tuned the model to replicate calcium uncaging experiments. The signaling network activity in single synapses switches between two discrete stable states (LTD and non-LTD) in a probabilistic manner. The stochasticity of the signaling network causes threshold dithering and allows at the macroscopic level for many different and stable mean magnitudes of depression. The probability of LTD occurrence in a single spine is only modulated by the concentration and duration of the signal used to trigger it, and inputs with the same magnitude can give rise to two different responses; there is no threshold for the input signal. The stochasticity is intrinsic to the signaling network and not mostly dependent on noise in the calcium input signal, as has been suggested previously. The activities of the ultrasensitive ERK and of cPLA(2) undergo strong stochastic fluctuations. Conversely, PKC, which acts as a noise filter, is more constantly activated. Systematic variation of the biochemical population size demonstrates that threshold dithering and the absence of spontaneous LTD depend critically on the number of molecules in a spine, indicating constraints on spine size in Purkinje cells.
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