The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Linking Context with Reward: A Functional Circuit from Hippocampal CA3 to Ventral Tegmental Area
Open accessAbstract
Reward-motivated behavior is strongly influenced by the learned significance of contextual stimuli in the environment. However, the neural pathways that mediate context-reward relations are not well understood. We have identified a circuit from area CA3 of dorsal hippocampus to ventral tegmental area (VTA) that uses lateral septum (LS) as a relay. Theta frequency stimulation of CA3 excited VTA dopamine (DA) neurons and inhibited non-DA neurons. DA neuron excitation was likely mediated by disinhibition because local antagonism of γ-aminobutyric acid receptors blocked responses to CA3 stimulation. Inactivating components of the CA3-LS-VTA pathway blocked evoked responses in VTA and also reinstatement of cocaine-seeking by contextual stimuli. This transsynaptic link between hippocampus and VTA appears to be an important substrate by which environmental context regulates goal-directed behavior.
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“this area serves as a hub in the brain by integrating social, emotional, and contextual information from different brain systems and contributing to the coordination of adaptive context-specific behavioral responses (Sheehan et al., 2004; Luo et al., 2011)”
From Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context (2014) · cites this paper as Luo et al., 2011
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“is necessary for the formation of cocaine conditioned place preference in rats [36,37].”
From Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin (2018) · cites this paper as [36]
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“and the lateral septum plays a key role in modulating context-specific motivational states (Sheehan et al., 2004; Luo et al., 2011; Sartor and Aston-Jones, 2012).”
From Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context (2014) · cites this paper as Luo et al., 2011
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“other studies indicating that the LS is part of the brain reward system.”
From Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin (2018) · cites this paper as [36]
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“Our results thus provide novel insights into the relationship between midbrain dopaminergic neurons, encoding salient information about an environment9,10,16,19,20, and hippocampal assemblies, providing representations of space1-3, in modulating memory according to the value of the information to be remembered.”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [16]
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“This VTA firing response to spatial novelty, which might be partially informed by hippocampal spatio-contextual inputs10,16, resulted in a higher fraction of action potentials discharged in bursts (interspike interval<50ms; novelty-induced burst ratio change=0.31±0.07, t156=4.31, P=2.9×10−5, paired t-test), a potentially suitable signal to in turn modulate hippocampal dynamics.”
From Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence (2014) · cites this paper as [16]
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Cites
Dopamine in motivational control: rewarding, aversive, and alerting
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.022 · Cited by 2,396
The hippocampal-VTA loop: controlling the entry of information into long-term memory
Lisman, J. E., & Grace, A. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.002 · Cited by 1,983
Opioids excite dopamine neurons by hyperpolarization of local interneurons
Johnson, S., & North, R. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00483.1992 · Cited by 1,637
Eichenbaum (2004) · doi:10.1016/j.neuron.2004.08.028 · Cited by 1,464
Adaptive Coding of Reward Value by Dopamine Neurons
Tobler, P. N., Fiorillo, C. D., & Schultz, W. (2005) · Science · doi:10.1126/science.1105370 · Cited by 1,276
Floresco, S., Todd, C. L., & Grace, A. A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04915.2001 · Cited by 556
Hasselmo, M. E. (2005) · Hippocampus · doi:10.1002/hipo.20116 · Cited by 502
Relapse to cocaine-seeking after hippocampal theta burst stimulation
Vorel, S. R., Liu, X., Hayes, R. J., Spector, J. A., & Gardner, E. L. (2001) · Science · doi:10.1126/science.1058043 · Cited by 486
Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions
Geisler, S., & Zahm, D. S. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20668 · Cited by 379
Card, J. P., Rinaman, L., Lynn, R., Bh, L., Meade, R. P., Miselis, R. R., & Enquist, L. W. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-06-02515.1993 · Cited by 317
Neurobiology of relapse to heroin and cocaine seeking: An update and clinical implications
Bossert, J. M., Ghitza, U. E., Lü, L., Epstein, D. H., & Shaham, Y. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.09.030 · Cited by 271
Swanson, L. W., Sawchenko, P. E., & Cowan, W. M. (1981) · Journal of Neuroscience · doi:10.1523/jneurosci.01-05-00548.1981 · Cited by 245
Fuchs, R. A., Eaddy, J. L., Su, Z., & Bell, G. H. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05674.x · Cited by 212
Legault, M., Rompré, P.-P., & Wise, R. A. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-04-01635.2000 · Cited by 200
Self-citationLuo, A. H., & Aston‐Jones, G. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06606.x · Cited by 154
Self-citationDifferent CA1 and CA3 Representations of Novel Routes in a Shortcut Situation
Alvernhe, A., Cauter, T. V., Save, É., & Poucet, B. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1909-08.2008 · Cited by 85
DeFrance, J. F., Kitai, S. T., & Shimono, T. (1973) · Experimental Brain Research · doi:10.1007/bf00234861 · Cited by 73
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“The representation strengths of memories and planning (served by PFChippocampus circuits) are often strongly affected by associated values (served by basal ganglia circuits; Luo et al., 2011).”
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Metadata
- Authors
- Luo, A. H., Tahsili-Fahadan, P., Wise, R. A., Lupica, C. R., & Aston-Jones, G.
- Affiliations
- National Institutes of Health (US)
- Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
- Corresponding author
- Luo, Alice H.
- Venue
- Science
- Published
- 2011-07-15
- Volume
- 333
- Issue
- 6040
- Pages
- 353-357
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3150711
- OpenAlex
- W2013438045
- Cited by
- 425
- References
- 17
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 30 · 2023: 18 · 2022: 29 · 2021: 29 · 2020: 28 · 2019: 22 · 2018: 30 · 2017: 32 · 2016: 32 · 2015: 37 · 2014: 39 · 2013: 31 · 2012: 23
- FWCI
- 13.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (F31MH071093)
- National Institute on Drug Abuse (R37DA006214, ZIADA000471)
- National Center for Research Resources (UL1RR029882)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampal CA3, ventral tegmental area, lateral septum, dopaminergic neurons, disinhibition, GABA receptors, cocaine seeking, reinstatement, goal-directed behavior, contextual cues, neural circuits
- MeSH terms
- Action Potentials, Animals, Behavior, Animal, Brain Mapping, Cocaine, Dopamine, Electric Stimulation, gamma-Aminobutyric Acid, Hippocampus, Male, Models, Neurological, Neural Inhibition, Neural Pathways, Neurons, Reward, Self Administration, Septal Nuclei, Theta Rhythm, Rats, Sprague-Dawley, Ventral Tegmental Area, GABA Agonists, GABA Antagonists, Rats, CA3 Region, Hippocampal, Drug-Seeking Behavior
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