ArticlePLoS computational biology2012
Subcellular location of PKA controls striatal plasticity: stochastic simulations in spiny dendrites.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 60 citations in OpenAlex.
- Calcium dynamics in small spaces: Lessons learned from modeling in dendritic spines.Biophysical journal · 2025Review
- In silico investigation of the puzzling dopamine effects on excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.Scientific reports · 2025Article
- Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons.Nature communications · 2024Article
- 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
- Reaction-diffusion models in weighted and directed connectomes.PLoS computational biology · 2022Article
- Computational investigation of the dynamic control of cAMP signaling by PDE4 isoform types.Biophysical journal · 2022Article
- Review
- Review
- Computational Modeling Reveals Frequency Modulation of Calcium-cAMP/PKA Pathway in Dendritic Spines.Biophysical journal · 2019Article
- Geometric Control of Frequency Modulation of cAMP Oscillations due to Calcium in Dendritic Spines.Biophysical journal · 2019Article
- From membrane receptors to protein synthesis and actin cytoskeleton: Mechanisms underlying long lasting forms of synaptic plasticity.Seminars in cell & developmental biology · 2019Review
- Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking.The European journal of neuroscience · 2019Article
- Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.Chemical reviews · 2018Review
- Competitive Tuning Among CaCellular and molecular bioengineering · 2018Article
- Article
- Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Dendritic geometry shapes neuronal cAMP signalling to the nucleus.Nature communications · 2015Article
- Mechanisms of dopamine D1 receptor-mediated ERK1/2 activation in the parkinsonian striatum and their modulation by metabotropic glutamate receptor type 5.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity.Nature neuroscience · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Dopamine release in the striatum has been implicated in various forms of reward dependent learning. Dopamine leads to production of cAMP and activation of protein kinase A (PKA), which are involved in striatal synaptic plasticity and learning. PKA and its protein targets are not diffusely located throughout the neuron, but are confined to various subcellular compartments by anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Experiments have shown that blocking the interaction of PKA with AKAPs disrupts its subcellular location and prevents LTP in the hippocampus and striatum; however, these experiments have not revealed whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. We have developed a large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines, based on published biochemical measurements, to investigate this question and to evaluate whether dopamine signaling exhibits spatial specificity post-synaptically. The model was stimulated with dopamine pulses mimicking those recorded in response to reward. Simulations show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase. Simulations further demonstrate that though cAMP exhibits a strong spatial gradient, diffusible DARPP-32 facilitates the spread of PKA activity, suggesting that additional inactivation mechanisms are required to produce spatial specificity of PKA activity.
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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.