The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses
Open accessAbstract
Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity 1,2 and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus-NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus-NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour.
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In the citing paper
“Activity-dependent LTP in vivo was both necessary and sufficient to induce a conditioned place preference lasting for at least 24hrs [193].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [193]
Experimental — accuracy not yet measuredIn the citing paper
“Both AMPAR-and NMDAR-components of the EPSP were equally affected, unlike in the NAc [192,193] and hippocampus [110].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [193]
In the citing paper
“Much like canonical hippocampal LTP, high frequency stimulation of hippocampal afferents to the NAc elicits a rapid and persistent NMDAR-triggered, Ca 2+ -and CaMKdependent increase in postsynaptic AMPAR responses in D1 and D2 MSNs [193].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [193]
In the citing paper
“Similarly, evoked AMPA receptor-mediated excitatory synaptic currents are reduced by chronic stress in D1, but not D2, MSNs [236], including in response to afferents from the hippocampus [193].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [193]
In the citing paper
“Chronic, but not acute, administration of fluoxetine to stressed mice restores the strength of hippocampal excitatory synapses in D1 MSNs and their ability to undergo LTP, concomitant with restoration of sucrose preference [193].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [193]
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Citations
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Metadata
- Authors
- LeGates, T. A., Kvarta, M. D., Tooley, J. R., Francis, T. C., Lobo, M. K., Creed, M. C., & Thompson, S. M.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Thompson, Scott M.
- ORCID
- Venue
- Nature
- Published
- 2018-11-26
- Volume
- 564
- Issue
- 7735
- Pages
- 258-262
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6292781
- OpenAlex
- W2900803145
- Cited by
- 290
- References
- 23
- Citations by year
- 2026: 36 · 2025: 33 · 2024: 41 · 2023: 36 · 2022: 41 · 2021: 45 · 2020: 25 · 2019: 30 · 2018: 1
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH106500, R01MH086828)
- National Institute on Drug Abuse (R01DA038613)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampus, nucleus accumbens, long-term potentiation, synaptic plasticity, conditioned place preference, anhedonia, chronic stress, antidepressant treatment, goal-directed behavior
- MeSH terms
- Animals, Chronic Disease, Conditioning, Psychological, Dopamine, Female, Goals, Hippocampus, Male, Neuronal Plasticity, Nucleus Accumbens, Reward, Stress, Psychological, Synapses, Long-Term Potentiation, Mice, Anhedonia
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