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Cortico-Basal Ganglia Reward Network: Microcircuitry
Open accessAbstract
Many of the brain's reward systems converge on the nucleus accumbens, a region richly innervated by excitatory, inhibitory, and modulatory afferents representing the circuitry necessary for selecting adaptive motivated behaviors. The ventral subiculum of the hippocampus provides contextual and spatial information, the basolateral amygdala conveys affective influence, and the prefrontal cortex provides an integrative impact on goal-directed behavior. The balance of these afferents is under the modulatory influence of dopamine neurons in the ventral tegmental area. This midbrain region receives its own complex mix of excitatory and inhibitory inputs, some of which have only recently been identified. Such afferent regulation positions the dopamine system to bias goal-directed behavior based on internal drives and environmental contingencies. Conditions that result in reward promote phasic dopamine release, which serves to maintain ongoing behavior by selectively potentiating ventral subicular drive to the accumbens. Behaviors that fail to produce an expected reward decrease dopamine transmission, which favors prefrontal cortical-driven switching to new behavioral strategies. As such, the limbic reward system is designed to optimize action plans for maximizing reward outcomes. This system can be commandeered by drugs of abuse or psychiatric disorders, resulting in inappropriate behaviors that sustain failed reward strategies. A fuller appreciation of the circuitry interconnecting the nucleus accumbens and ventral tegmental area should serve to advance discovery of new treatment options for these conditions.
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“Multiple cortical (Finch, 1996; Sesack and Grace, 2010) and amygdala (McGinty and Grace, 2009) inputs converge onto the same NAc neurons.”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Sesack and Grace, 2010
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“A grossly oversimplified overview of these circuits is that the prefrontal cortices and hippocampus are devoted to detecting and decoding specific features of stimuli and the environment, including the social environment, to guide decision-making and ensure adaptive, flexible, and predictive responses to rewarding stimuli, whereas the lateral hypothalamus-lateral habenula circuits predominantly En”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [50]
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“Although several brain structures contribute to the reward circuitry, the central hub within this functional network is the ventral striatum (VS) [10].”
From Social “wanting” dysfunction in autism: neurobiological underpinnings and treatment implications (2012) · cites this paper as [10]
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Metadata
- Authors
- Sesack, S. R., & Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Sesack, Susan R
- Grace, Anthony A
- Venue
- Neuropsychopharmacology
- Published
- 2009-08-12
- Volume
- 35
- Issue
- 1
- Pages
- 27-47
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2879005
- OpenAlex
- W1971690948
- Cited by
- 985
- References
- 359
- Citations by year
- 2026: 33 · 2025: 40 · 2024: 48 · 2023: 37 · 2022: 46 · 2021: 59 · 2020: 51 · 2019: 57 · 2018: 58 · 2017: 69 · 2016: 87 · 2015: 78 · 2014: 85 · 2013: 86 · 2012: 76
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R37MH057440)
- National Institute on Drug Abuse (R01DA015408)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- reward systems, nucleus accumbens, ventral tegmental area, dopamine, ventral subiculum, basolateral amygdala, prefrontal cortex, hippocampus, microcircuitry, goal-directed behavior, phasic dopamine release, drug addiction, mental illness, afferent input
- MeSH terms
- Animals, Basal Ganglia, Cerebral Cortex, Humans, Models, Neurological, Neural Pathways, Nucleus Accumbens, Reward, Ventral Tegmental Area
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