Journal
LEARNING & MEMORY
Volume 22, Issue 10, Pages 499-508Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/lm.039222.115
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Funding
- Canadian Institutes of Health Research [MOP-114994, MOP-74453]
- Azrielli/Brain Canada
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Norepinephrine (NE) is a key modulator of synaptic plasticity in the hippocampus, a brain structure crucially involved in memory formation. NE boosts synaptic plasticity mostly through initiation of signaling cascades downstream from beta (beta)-adrenergic receptors (beta-ARs). Previous studies demonstrated that a beta-adrenergic receptor agonist, isoproterenol, can modify the threshold for long-term potentiation (LTP), a putative cellular mechanism for learning and memory, in a process known as metaplasticity. Metaplasticity is the ability of synaptic plasticity to be modified by prior experience. We asked whether NE itself could engage metaplastic mechanisms in area CA1 of mouse hippocampal slices. Using extracellular field potential recording and stimulation, we show that application of NE (10 mu M), which did not alter basal synaptic strength, enhances the future maintenance of LTP elicited by subthreshold, high-frequency stimulation (HFS: 1 x 100 Hz, 1 sec). HFS applied 30 min after NE washout induced long-lasting (>4 h) LTP, which was significantly extended in duration relative to HFS alone. This NE-induced metaplasticity required beta 1-AR activation, as coapplication of the beta 1-receptor antagonist CGP-20712A (1 mu M) attenuated maintenance of LTP. We also found that NE-mediated metaplasticity was translation and transcription-dependent. Polysomal profiles of CA1 revealed increased translation rates for specific mRNAs during NE-induced metaplasticity. Thus, activation of beta-ARs by NE primes synapses for future long-lasting plasticity on time scales extending beyond fast synaptic transmission; this may facilitate neural information processing and the subsequent formation of lasting memories.
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