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The Journal of Neuroscience, August 15, 2000, 20(16):5924-5931
Coactivation of -Adrenergic and Cholinergic Receptors Enhances
the Induction of Long-Term Potentiation and Synergistically Activates
Mitogen-Activated Protein Kinase in the Hippocampal CA1 Region
Ayako M.
Watabe1,
Paulette A.
Zaki2, and
Thomas J.
O'Dell1
1 Department of Physiology, University of California,
Los Angeles School of Medicine and 2 Interdepartmental PhD
Program for Neuroscience, University of California, Los Angeles, Los
Angeles, California 90095
Interactions between noradrenergic and cholinergic receptor
signaling may be important in some forms of learning. To
investigate whether noradrenergic and cholinergic receptor interactions
regulate forms of synaptic plasticity thought to be involved in memory formation, we examined the effects of concurrent -adrenergic and
cholinergic receptor activation on the induction of long-term potentiation (LTP) in the hippocampal CA1 region. Low concentrations of
the -adrenergic receptor agonist isoproterenol (ISO) and the cholinergic receptor agonist carbachol had no effect on the induction of LTP by a brief train of 5 Hz stimulation when applied individually but dramatically facilitated LTP induction when coapplied. Although carbachol did not enhance ISO-induced increases in cAMP, coapplication of ISO and carbachol synergistically activated p42 mitogen-activated protein kinase (p42 MAPK). This suggests that concurrent -adrenergic and cholinergic receptor activation enhances LTP induction by activating MAPK and not by additive or synergistic effects on adenylyl
cyclase. Consistent with this, blocking MAPK activation with MEK
inhibitors suppressed the facilitation of LTP induction produced by
concurrent -adrenergic and cholinergic receptor activation. Although
MEK inhibitors also suppressed the induction of LTP by a stronger 5 Hz
stimulation protocol that induced LTP in the absence of ISO and
carbachol, they had no effect on LTP induced by high-frequency synaptic
stimulation or low-frequency synaptic stimulation paired with
postsynaptic depolarization. Our results indicate that MAPK activation
has an important, modulatory role in the induction of LTP and suggest
that coactivation of noradrenergic and cholinergic receptors regulates
LTP induction via convergent effects on MAPK.
Key words:
long-term potentiation; -adrenergic receptors; cholinergic receptors; adenylyl cyclase; mitogen-activated protein
kinase; hippocampus
Copyright © 2000 Society for Neuroscience 0270-6474/00/20165924-08$05.00/0
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