ArticleProceedings of the National Academy of Sciences of the United States of America2016
Calcium threshold shift enables frequency-independent control of plasticity by an instructive signal.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Synchronous climbing fiber activity enables instructive signaling for cerebellar learning through modulation of disinhibitory circuits.Nature neuroscience · 2026Article
- Cerebellum violates Marr-Albus predictions to train synapses on long-term anticipatory goals.bioRxiv : the preprint server for biology · 2026Article
- Cerebellar climbing fibers impact experience-dependent plasticity in the mouse primary somatosensory cortex.eLife · 2025Article
- Cerebellar climbing fibers impact experience-dependent plasticity in the mouse primary somatosensory cortex.bioRxiv : the preprint server for biology · 2025Article
- MicroRNAs modulate CaMKIIα/SIRT1 signaling pathway as a biomarker of cognitive ability in adolescents.Brain, behavior, & immunity - health · 2025Article
- The calcitron: A simple neuron model that implements many learning rules via the calcium control hypothesis.PLoS computational biology · 2025Article
- Article
- Different Numbers of Conjunctive Stimuli Induce LTP or LTD in Mouse Cerebellar Purkinje Cell.Cerebellum (London, England) · 2024Article
- Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact.Cerebellum (London, England) · 2024Article
- Intrinsic and synaptic determinants of receptive field plasticity in Purkinje cells of the mouse cerebellum.Nature communications · 2024Article
- Contiguity in perception: origins in cellular associative computations.Trends in neurosciences · 2024Review
- Neural ensembles: role of intrinsic excitability and its plasticity.Frontiers in cellular neuroscience · 2024Review
- Climbing fiber multi-innervation of mouse Purkinje dendrites with arborization common to human.Science (New York, N.Y.) · 2023Article
- Asymmetric Voltage Attenuation in Dendrites Can Enable Hierarchical Heterosynaptic Plasticity.eNeuro · 2023Article
- Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus.Frontiers in cellular neuroscience · 2023Article
- Gating by Memory: a Theory of Learning in the Cerebellum.Cerebellum (London, England) · 2022Article
- Long-term depression-inductive stimulation causes long-term potentiation in mouse Purkinje cells with a mutant thyroid hormone receptor.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Sensory Over-responsivity and Aberrant Plasticity in Cerebellar Cortex in a Mouse Model of Syndromic Autism.Biological psychiatry global open science · 2022Article
- A Modeling and Analysis Study Reveals That CaMKII in Synaptic Plasticity Is a Dominant Affecter in CaM Systems in a T286 Phosphorylation-Dependent Manner.Molecules (Basel, Switzerland) · 2022Article
- The calcium sensor, rather than the route of calcium entry, defines cerebellar plasticity pathways.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
At glutamatergic synapses, both long-term potentiation (LTP) and long-term depression (LTD) can be induced at the same synaptic activation frequency. Instructive signals determine whether LTP or LTD is induced, by modulating local calcium transients. Synapses maintain the ability to potentiate or depress over a wide frequency range, but it remains unknown how calcium-controlled plasticity operates when frequency variations alone cause differences in calcium amplitudes. We addressed this problem at cerebellar parallel fiber-Purkinje cell synapses, which can undergo LTD or LTP in response to 1-Hz and 100-Hz stimulation. We observed that high-frequency activation elicits larger spine calcium transients than low-frequency stimulation under all stimulus conditions, but, regardless of activation frequency, climbing fiber (CF) coactivation provides an instructive signal that further enhances calcium transients and promotes LTD. At both frequencies, buffering calcium prevents LTD induction and LTP results instead, identifying the enhanced calcium signal amplitude as the critical parameter contributed by the instructive CF signal. These observations show that it is not absolute calcium amplitudes that determine whether LTD or LTP is evoked but, instead, the LTD threshold slides, thus preserving the requirement for relatively larger calcium transients for LTD than for LTP induction at any given stimulus frequency. Cerebellar LTD depends on the activation of calcium/calmodulin-dependent kinase II (CaMKII). Using genetically modified (TT305/6VA and T305D) mice, we identified α-CaMKII inhibition upon autophosphorylation at Thr305/306 as a molecular event underlying the threshold shift. This mechanism enables frequency-independent plasticity control by the instructive CF signal based on relative, not absolute, calcium thresholds.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.