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Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory
Open accessAbstract
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 (Ressler and Nemeroff, 1999), cognition(Hoshino, 2005) and perception (Mather et al., 2016).”
From Efficacy, acceptability and side-effects of oral versus long-acting- injectables antipsychotics: Systematic review and network meta-analysis (2024) · cites this paper as Mather et al., 2016
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“Release of norepinephrine by the locus coeruleus influences arousal levels and has been shown to prioritize processing of goal-relevant information and to promote memory formation in the hippocampus (Clewett et al., 2018; Mather et al., 2016).”
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Self-citation
Metadata
- 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
- 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
- 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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