Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory
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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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These neurotransmitters play a key role in mood regulation, cognition, and perception.
“These neurotransmitters play a key role in mood regulation (Ressler and Nemeroff, 1999), cognition(Hoshino, 2005) and perception (Mather et al., 2016).”
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- Rasch B Spalek K Buholzer S Luechinger R Boesiger P Papassotiropoulos A Quervain DJFd 2009 A genetic variation of the noradrenergic system is related to differential amygdala activation during encoding of emotional memories Proceedings of the National Academy of Sciences of the United States of America 106 45 19191 19196 10.2307/25593165 19826083 PMC2761241 · DOI
- Sutherland MR Mather M (under review) Both positive and negative arousing sounds increase the impact of visual salience
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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)
- 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
- PMC
- PMC5830137
- OpenAlex
- W2126712529
- Cited by
- 695
- References
- 402
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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