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The Journal of Neuroscience, March 30, 2005, 25(13):3294-3303; doi:10.1523/JNEUROSCI.4175-04.2005

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Cellular/Molecular
{beta}-Adrenergic Receptor Activation Facilitates Induction of a Protein Synthesis-Dependent Late Phase of Long-Term Potentiation

Jennifer N. Gelinas1 and Peter V. Nguyen1,2,3

Departments of 1Physiology and 2Psychiatry and 3Centre for Neuroscience, University of Alberta School of Medicine, Edmonton, Alberta, Canada T6G 2H7

Long-term potentiation (LTP) is activity-dependent enhancement of synaptic strength that can critically regulate long-term memory storage. Like memory, LTP exhibits at least two mechanistically distinct temporal phases. Early LTP (E-LTP) does not require protein synthesis, whereas the late phase of LTP (L-LTP), like long-term memory, requires protein synthesis. Hippocampal {beta}-adrenergic receptors can regulate expression of both E-LTP and long-term memory. Although {beta}-adrenergic receptor activation enhances the ability of subthreshold stimuli to induce E-LTP, it is unclear whether such activation can facilitate induction of L-LTP. Here, we use electrophysiological recording methods on mouse hippocampal slices to show that when synaptic stimulation that is subthreshold for inducing L-LTP is paired with {beta}-adrenergic receptor activation, the resulting LTP persists for over 6 h in area CA1. Like L-LTP induced by multiple trains of high-frequency electrical stimulation, this LTP requires protein synthesis. Unlike tetanus-induced L-LTP, however, L-LTP induced by {beta}-adrenergic receptor activation during subthreshold stimulation appears to involve dendritic protein synthesis but not somatic transcription. Maintenance of this LTP also requires activation of extracellular signal-regulated kinases (ERKs). Thus, {beta}-adrenergic receptor activation elicits a type of L-LTP that requires translation and ERK activation but not transcription. This form of L-LTP may be a cellular mechanism for facilitation of behavioral long-term memory during periods of heightened emotional arousal that engage the noradrenergic modulatory system.

Key words: noradrenergic receptors; LTP; hippocampus; protein synthesis; memory; neuromodulation

Received Oct 7, 2004; revised February 7, 2005; accepted February 11, 2005.




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