β-adrenergic signaling broadly contributes to LTP induction

Joanna Jȩdrzejewska-Szmek; Vincent Luczak; Ted Abel; Kim T Blackwell

doi:10.1371/journal.pcbi.1005657

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β-adrenergic signaling broadly contributes to LTP induction

Journal article

Open access

β-adrenergic signaling broadly contributes to LTP induction

Joanna Jȩdrzejewska-Szmek, Vincent Luczak, Ted Abel and Kim T Blackwell

PLoS computational biology, Vol.13(7), pp.e1005657-e1005657

07/2017

DOI: 10.1371/journal.pcbi.1005657

PMCID: PMC5546712

PMID: 28742159

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Abstract

Long-lasting forms of long-term potentiation (LTP) represent one of the major cellular mechanisms underlying learning and memory. One of the fundamental questions in the field of LTP is why different molecules are critical for long-lasting forms of LTP induced by diverse experimental protocols. Further complexity stems from spatial aspects of signaling networks, such that some molecules function in the dendrite and some are critical in the spine. We investigated whether the diverse experimental evidence can be unified by creating a spatial, mechanistic model of multiple signaling pathways in hippocampal CA1 neurons. Our results show that the combination of activity of several key kinases can predict the occurrence of long-lasting forms of LTP for multiple experimental protocols. Specifically Ca2+/calmodulin activated kinase II, protein kinase A and exchange protein activated by cAMP (Epac) together predict the occurrence of LTP in response to strong stimulation (multiple trains of 100 Hz) or weak stimulation augmented by isoproterenol. Furthermore, our analysis suggests that activation of the β-adrenergic receptor either via canonical (Gs-coupled) or non-canonical (Gi-coupled) pathways underpins most forms of long-lasting LTP. Simulations make the experimentally testable prediction that a complete antagonist of the β-adrenergic receptor will likely block long-lasting LTP in response to strong stimulation. Collectively these results suggest that converging molecular mechanisms allow CA1 neurons to flexibly utilize signaling mechanisms best tuned to temporal pattern of synaptic input to achieve long-lasting LTP and memory storage.

Animals

CA1 Region, Hippocampal - cytology

CA1 Region, Hippocampal - physiology

Signal Transduction

Calcium - metabolism

Dendrites - physiology

Long-Term Potentiation - physiology

Models, Neurological

Receptors, Adrenergic, beta - metabolism

Details

Title: Subtitle: β-adrenergic signaling broadly contributes to LTP induction
Creators: Joanna Jȩdrzejewska-Szmek - The Krasnow Institute for Advanced Studies, George Mason University, Fairfax, Virginia, United States of America
Vincent Luczak - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Kim T Blackwell - The Krasnow Institute for Advanced Studies, George Mason University, Fairfax, Virginia, United States of America
Resource Type: Journal article
Publication Details: PLoS computational biology, Vol.13(7), pp.e1005657-e1005657
DOI: 10.1371/journal.pcbi.1005657
PMID: 28742159
PMCID: PMC5546712
NLM abbreviation: PLoS Comput Biol
ISSN: 1553-734X
eISSN: 1553-7358
Publisher: United States
Grant note: R01 AA018060 / NIAAA NIH HHS
Language: English
Date published: 07/2017
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: 9984070720802771

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