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 ß-adrenergic receptors (ß-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 ß-ARs towards gating the expression of protein synthesis-dependent, long-lasting hippocampal LTP. We focus on the roles of ß-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.