Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation

Vincent Luczak; Kim T Blackwell; Ted Abel; Jean-Antoine Girault; Nicolas Gervasi

doi:10.1016/j.nlm.2016.08.006

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Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation

Journal article

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Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation

Vincent Luczak, Kim T Blackwell, Ted Abel, Jean-Antoine Girault and Nicolas Gervasi

Neurobiology of learning and memory, Vol.138, pp.10-20

02/2017

DOI: 10.1016/j.nlm.2016.08.006

PMCID: PMC5303694

PMID: 27523748

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https://hal.sorbonne-universite.fr/hal-01514938View

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Abstract

In the hippocampus, cyclic-adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) form a critical signaling cascade required for long-lasting synaptic plasticity, learning and memory. Plasticity and memory are known to occur following pathway-specific changes in synaptic strength that are thought to result from spatially and temporally coordinated intracellular signaling events. To better understand how cAMP and PKA dynamically operate within the structural complexity of hippocampal neurons, we used live two-photon imaging and genetically-encoded fluorescent biosensors to monitor cAMP levels or PKA activity in CA1 neurons of acute hippocampal slices. Stimulation of β-adrenergic receptors (isoproterenol) or combined activation of adenylyl cyclase (forskolin) and inhibition of phosphodiesterase (IBMX) produced cAMP transients with greater amplitude and rapid on-rates in intermediate and distal dendrites compared to somata and proximal dendrites. In contrast, isoproterenol produced greater PKA activity in somata and proximal dendrites compared to intermediate and distal dendrites, and the on-rate of PKA activity did not differ between compartments. Computational models show that our observed compartmental difference in cAMP can be reproduced by a uniform distribution of PDE4 and a variable density of adenylyl cyclase that scales with compartment size to compensate for changes in surface to volume ratios. However, reproducing our observed compartmental difference in PKA activity required enrichment of protein phosphatase in small compartments; neither reduced PKA subunits nor increased PKA substrates were sufficient. Together, our imaging and computational results show that compartment diameter interacts with rate-limiting components like adenylyl cyclase, phosphodiesterase and protein phosphatase to shape the spatial and temporal components of cAMP and PKA signaling in CA1 neurons and suggests that small neuronal compartments are most sensitive to cAMP signals whereas large neuronal compartments accommodate a greater dynamic range in PKA activity.

Cyclic AMP-Dependent Protein Kinases - metabolism

Dendrites - drug effects

Colforsin - pharmacology

Adrenergic beta-Agonists - pharmacology

Phosphodiesterase Inhibitors - pharmacology

Hippocampus - drug effects

1-Methyl-3-isobutylxanthine - pharmacology

Hippocampus - metabolism

Animals

Signal Transduction - drug effects

Dendrites - physiology

Isoproterenol - pharmacology

Mice

Models, Neurological

Phosphorylation - drug effects

Receptors, Adrenergic, beta - metabolism

Cyclic AMP - metabolism

Details

Title: Subtitle: Dendritic diameter influences the rate and magnitude of hippocampal cAMP and PKA transients during β-adrenergic receptor activation
Creators: Vincent Luczak - University of Pennsylvania, Department of Biology, 10-133 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USA
Kim T Blackwell - George Mason University, The Krasnow Institute for Advanced Studies, MS 2A1, Rockfish Creek Lane, Fairfax, VA 22030, USA
Ted Abel - University of Pennsylvania, Department of Biology, 10-133 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Building 421, Philadelphia, PA 19104, USA. Electronic address: abele@sas.upenn.edu
Jean-Antoine Girault - INSERM, UMR-S 839, 75005 Paris, France; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités, 75005 Paris, France; Institut du Fer à Moulin, 17 Rue du Fer à Moulin, 75005 Paris, France
Nicolas Gervasi - INSERM, UMR-S 839, 75005 Paris, France; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités, 75005 Paris, France; Institut du Fer à Moulin, 17 Rue du Fer à Moulin, 75005 Paris, France. Electronic address: nicolas.gervasi@inserm.fr
Resource Type: Journal article
Publication Details: Neurobiology of learning and memory, Vol.138, pp.10-20
DOI: 10.1016/j.nlm.2016.08.006
PMID: 27523748
PMCID: PMC5303694
NLM abbreviation: Neurobiol Learn Mem
ISSN: 1074-7427
eISSN: 1095-9564
Publisher: United States
Grant note: R01 MH086415 / NIMH NIH HHS 250349 / European Research Council R01 AA018060 / NIAAA NIH HHS
Language: English
Date published: 02/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984070339602771

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