Single-cell activity tracking reveals that orbitofrontal neurons acquire and maintain a long-term memory to guide behavioral adaptation
Open accessAbstract
Learning to predict rewards based on environmental cues is essential for survival. The orbitofrontal cortex (OFC) contributes to such learning by conveying reward-related information to brain areas such as the ventral tegmental area (VTA). Despite this, how cue-reward memory representations form in individual OFC neurons and are modified based on new information is unknown. To address this, using in vivo two-photon calcium imaging in mice, we tracked the response evolution of thousands of OFC output neurons, including those projecting to VTA, through multiple days and stages of cue-reward learning. Collectively, we show that OFC contains several functional clusters of neurons distinctly encoding cue-reward memory representations, with only select responses routed downstream to VTA. Unexpectedly, these representations were stably maintained by the same neurons even after extinction of the cue-reward pairing, and supported behavioral learning and memory. Thus, OFC neuronal activity represents a long-term cue-reward associative memory to support behavioral adaptation.
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The OFC may have direct connections to the ventral tegmental area in mice where dopamine neurons are located.
“The OFC may also have direct connections to the ventral tegmental area in mice where dopamine neurons are located (Namboodiri et al., 2019).”
From The orbitofrontal cortex: reward, emotion and depression (2020) · cites this paper as Namboodiri et al., 2019
The orbitofrontal cortex is a source of reward-related information that reaches the dopamine neurons in the brainstem.
“the OFC is a source of reward-related information that reaches the dopamine neurons in the brainstem (Rolls, 2017; Namboodiri et al., 2019) (Fig. 2)”
From The orbitofrontal cortex: reward, emotion and depression (2020) · cites this paper as Namboodiri et al., 2019
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The orbitofrontal cortex: reward, emotion and depression
Rolls, E. T., Cheng, W., & Feng, J. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa196 · Cited by 474 · see citing works
Is the core function of orbitofrontal cortex to signal values or make predictions?
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- Authors
- Namboodiri, V. M. K., Otis, J. M., van Heeswijk, K., Voets, E. S., Alghorazi, R. A., Rodriguez-Romaguera, J., Mihalas, S., & Stuber, G. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Stuber, Garret D.
- Venue
- Nature Neuroscience
- Published
- 2019-06-03
- Volume
- 22
- Issue
- 7
- Pages
- 1110-1121
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC7002110
- OpenAlex
- W2948268330
- Cited by
- 150
- References
- 63
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 31 · 2023: 22 · 2022: 19 · 2021: 21 · 2020: 20 · 2019: 5
- FWCI
- 9.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Howard Hughes Medical Institute
- Brain and Behavior Research Foundation
- National Institute of Mental Health (F32MH113327)
- National Institute on Drug Abuse (R01DA032750, F32DA041184, R01DA038168, R37DA032750)
- National Institute of Neurological Disorders and Stroke (P30NS045892)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- orbitofrontal cortex, associative memory, long-term memory, ventral tegmental area, memory extinction, behavioral adaptation, two-photon calcium imaging
- MeSH terms
- Acoustic Stimulation, Adaptation, Psychological, Animals, Association Learning, Conditioning, Classical, Cues, Drinking Behavior, Extinction, Psychological, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurons, Reward, Prefrontal Cortex, Ventral Tegmental Area, Patch-Clamp Techniques, Calcium Signaling, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Memory, Long-Term, Single-Cell Analysis, Optogenetics
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