Noradrenergic gating of long-lasting synaptic potentiation in the hippocampus: from neurobiology to translational biomedicine

Abstract

Altered synaptic strength underlies information storage in neural circuits. Neuromodulatory transmitters such as norepinephrine (NE) facilitate long-lasting synaptic plasticity by recruiting and modifying multiple molecular elements of synaptic signaling, including specific transmitter receptors, intracellular protein kinases, and translation initiation. NE regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors (β-ARs), which bind NE and are critical for gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in neural circuits. In this article, in honor of Prof. Harold Atwood, we review the contributions of β-ARs towards gating the expression of protein synthesis-dependent, long-lasting hippocampal LTP. We focus on the roles of β-ARs in modifying ion channels, glutamatergic AMPA receptors, and translation initiation factors during LTP. We discuss prospective research strategies that may lead to increased understanding of the roles of NE in regulating neural circuit physiology; these may uncover novel therapies for treatment of specific neurological disorders linked to aberrant circuit activity and dysfunctional noradrenergic synaptic transmission.

Keywords:

• Noradrenaline
• synaptic plasticity
• beta-adrenergic receptors
• hippocampus
• neural circuits

Acknowledgements

We thank Marla Sokolowski and Jeffrey Dason for their kind invitations to contribute to this special issue. We also gratefully acknowledge the scientific contributions of our many collaborators and former trainees. We apologize to colleagues whose research contributions were not covered here because of space restrictions.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

P. Nguyen’s research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (Grant #203197) and the Canadian Institutes of Health Research. (Grants MOP 74453, 137357) J. Gelinas received funding from the Pediatric Scientist Development Program and March of Dimes. Her research is also supported by Columbia University Medical Center, Institute for Genomic Medicine and Department of Neurology.