ArticlePLoS computational biology2016
Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- GPCR signaling via cAMP nanodomains.The Biochemical journal · 2025Review
- Impact of early β-blocker use on the incidence of sepsis and clinical outcomes following cardiac surgery: a retrospective cohort study.Frontiers in pharmacology · 2025Article
- Fitting and comparison of calcium-calmodulin kinetic schemes to a common data set using non-linear mixed effects modelling.PloS one · 2025Article
- Norepinephrine triggers glutamatergic long-term potentiation in hypothalamic paraventricular nucleus magnocellular neuroendocrine cells through postsynaptic β1-AR/PKA signaling pathwayThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway.iScience · 2023Article
- Computational investigation of the dynamic control of cAMP signaling by PDE4 isoform types.Biophysical journal · 2022Article
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Stress-Induced Enhanced Long-Term Potentiation and Reduced Threshold for N-Methyl-D-Aspartate Receptor- and β-Adrenergic Receptor-Mediated Synaptic Plasticity in Rodent Ventral Subiculum.Frontiers in molecular neuroscience · 2021Article
- 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
- Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: A Steered-Glutamatergic Perspective.Brain sciences · 2019Review
- Locus Coeruleus Phasic, But Not Tonic, Activation Initiates Global Remapping in a Familiar Environment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Competitive Tuning Among CaCellular and molecular bioengineering · 2018Article
- Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction.PLoS computational biology · 2018Article
- Challenges in Reproducibility, Replicability, and Comparability of Computational Models and Tools for Neuronal and Glial Networks, Cells, and Subcellular Structures.Frontiers in neuroinformatics · 2018Article
- Article
- β-adrenergic signaling broadly contributes to LTP induction.PLoS computational biology · 2017Article
- Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation.Neurobiology of learning and memory · 2017Article
- Loss of Catecholaminergic Neuromodulation of Persistent Forms of Hippocampal Synaptic Plasticity with Increasing Age.Frontiers in synaptic neuroscience · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs), facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP) at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs). To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA), and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory.
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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.