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Rapid strengthening of thalamo-amygdala synapses mediates cue–reward learning
Open accessAbstract
What neural changes underlie individual differences in goal-directed learning? The lateral amygdala (LA) is important for assigning emotional and motivational significance to discrete environmental cues, including those that signal rewarding events. Recognizing that a cue predicts a reward enhances an animal's ability to acquire that reward; however, the cellular and synaptic mechanisms that underlie cue-reward learning are unclear. Here we show that marked changes in both cue-induced neuronal firing and input-specific synaptic strength occur with the successful acquisition of a cue-reward association within a single training session. We performed both in vivo and ex vivo electrophysiological recordings in the LA of rats trained to self-administer sucrose. We observed that reward-learning success increased in proportion to the number of amygdala neurons that responded phasically to a reward-predictive cue. Furthermore, cue-reward learning induced an AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated increase in the strength of thalamic, but not cortical, synapses in the LA that was apparent immediately after the first training session. The level of learning attained by individual subjects was highly correlated with the degree of synaptic strength enhancement. Importantly, intra-LA NMDA (N-methyl-d-aspartate)-receptor blockade impaired reward-learning performance and attenuated the associated increase in synaptic strength. These findings provide evidence of a connection between LA synaptic plasticity and cue-reward learning, potentially representing a key mechanism underlying goal-directed behaviour.
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“In this way, cues predicting threat are themselves recognized as threatening60 and, likewise, those predicting reward themselves become rewarding61,62.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [62]
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“In addition to being essential for aversively motivated learning, plasticity in the LA is also required for several forms of appetitively motivated learning (43–45) and a number of studies have found that separate populations of amygdala neurons mediate aversive and appetitive processing (46–48).”
From Optical activation of lateral amygdala pyramidal cells instructs associative fear learning (2010) · cites this paper as [45]
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“The BLA is critical for associative learning”
From Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility (2026) · cites this paper as [29]
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Metadata
- Authors
- Tye, K. M., Stuber, G. D., de Ridder, B., Bonci, A., & Janak, P. H.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Janak, Patricia H.
- Venue
- Nature
- Published
- 2008-05-11
- Volume
- 453
- Issue
- 7199
- Pages
- 1253-1257
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2759353
- OpenAlex
- W2011521010
- Cited by
- 216
- References
- 31
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 6 · 2023: 3 · 2022: 14 · 2021: 16 · 2020: 12 · 2019: 16 · 2018: 14 · 2017: 16 · 2016: 13 · 2015: 14 · 2014: 14 · 2013: 8 · 2012: 16
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Drug Abuse (R01DA015096, R01DA115096)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- lateral amygdala, synaptic plasticity, AMPA receptors, NMDA receptor blockade, individual differences in learning, sucrose self-administration, reward prediction, goal-directed learning, rats, drug addiction, eating disorders, emotional learning, NMDA receptor
- MeSH terms
- Amygdala, Animals, Cues, Learning, Male, Models, Neurological, Reward, Synapses, Thalamus, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Rats, Sprague-Dawley, Receptors, AMPA, Excitatory Postsynaptic Potentials, Rats
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