Cited by 741Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeural dynamics and brain function

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Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory

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Mather, Mara, Clewett, David, Sakaki, Michiko, Harley, Carolyn W.·2016·Behavioral and Brain Sciences

DOI 10.1017/s0140525x15000667PMC PMC5830137

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Abstract

Emotional arousal enhances perception and memory of high-priority information but impairs processing of other information. Here, we propose that, under arousal, local glutamate levels signal the current strength of a representation and interact with norepinephrine (NE) to enhance high priority representations and out-compete or suppress lower priority representations. In our "glutamate amplifies noradrenergic effects" (GANE) model, high glutamate at the site of prioritized representations increases local NE release from the locus coeruleus (LC) to generate "NE hotspots." At these NE hotspots, local glutamate and NE release are mutually enhancing and amplify activation of prioritized representations. In contrast, arousal-induced LC activity inhibits less active representations via two mechanisms: 1) Where there are hotspots, lateral inhibition is amplified; 2) Where no hotspots emerge, NE levels are only high enough to activate low-threshold inhibitory adrenoreceptors. Thus, LC activation promotes a few hotspots of excitation in the context of widespread suppression, enhancing high priority representations while suppressing the rest. Hotspots also help synchronize oscillations across neural ensembles transmitting high-priority information. Furthermore, brain structures that detect stimulus priority interact with phasic NE release to preferentially route such information through large-scale functional brain networks. A surge of NE before, during, or after encoding enhances synaptic plasticity at NE hotspots, triggering local protein synthesis processes that enhance selective memory consolidation. Together, these noradrenergic mechanisms promote selective attention and memory under arousal. GANE not only reconciles apparently contradictory findings in the emotion-cognition literature but also extends previous influential theories of LC neuromodulation by proposing specific mechanisms for how LC-NE activity increases neural gain.

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Authors: Mather, M., Clewett, D., Sakaki, M., & Harley, C. W.
Affiliations: University of Southern California (US)
Kochi University of Technology (JP)
Memorial University of Newfoundland (CA)
ORCID: Mather, Mara
Clewett, David
Sakaki, Michiko
Harley, Carolyn W.
Venue: Behavioral and Brain Sciences
Publisher: Cambridge University Press (CUP)
Published: 2015-07-01
Volume: 39
Pages: e200-e200
ISSN: 0140-525X (ISSN-L)
1469-1825
DOI: 10.1017/s0140525x15000667
PMC: PMC5830137
OpenAlex: W2126712529
Cited by: 695
References: 399
Citations by year: 2026: 70 · 2025: 79 · 2024: 59 · 2023: 86 · 2022: 66 · 2021: 87 · 2020: 65 · 2019: 49 · 2018: 53 · 2017: 43 · 2016: 32 · 2015: 5
FWCI: 26.68
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.cambridge.org/core/terms (unspecified)
Locations: Behavioral and Brain Sciences (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
CentAUR (University of Reading) (acceptedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Funders: National Institute on Aging (R01AG025340)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords: norepinephrine, locus coeruleus, emotional arousal, glutamate, neural gain, selective attention, memory consolidation, lateral inhibition, adrenergic receptors, neural oscillations, synaptic plasticity, emotion-cognition interaction
MeSH terms: Arousal, Attention, Humans, Locus Coeruleus, Memory, Norepinephrine

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Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory

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