ArticleNeuron2024
D1 and D2 medium spiny neurons in the nucleus accumbens core have distinct and valence-independent roles in learning.
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Article in Neuron, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49citing papers in PubMed
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49 citing papers in PubMed.
- Exercise as a Neurobiological Intervention: Utilizing NAc Circuitry to Combat Addiction.Addiction neuroscience · 2026Article
- Amygdalostriatal transition zone neurons encode sustained cue responses to guide defensive behaviors.Neuron · 2026Article
- Dopamine D2 receptors bypass canonical signaling to directly tune NMDA receptor function and aversive learning.Science advances · 2026Article
- Learning dynamically regulates stimulus discrimination of ventral striatal D1 receptor expressing neurons.Science advances · 2026Article
- The Endogenous Opioid System in Compulsive Eating.Brain sciences · 2026Review
- DRD1 and DRD2 dopamine-sensitive neurons in the central amygdala respond differently to rewarding and aversive stimuli.Translational psychiatry · 2026Article
- BDNF restores impaired long-term potentiation of GABAergic synapses induced by chronic ethanol exposure in the VTA and attenuates reward-seeking behavior.Molecular psychiatry · 2026Article
- Nucleus accumbens medial shell D1 and D2 medium spiny neurons signal the valence of conditioned stimuli in a sex-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Social Novelty Recruits a Dysfunctional Nucleus Accumbens Ensemble That Drives Social Avoidance in abioRxiv : the preprint server for biology · 2026Article
- Inherited input and local transformations shape the spatiotemporal organization of pathway specific striatal signals for motivated behavior.bioRxiv : the preprint server for biology · 2026Article
- Thyroid-stimulating hormone receptor mediates peripheral-central neuroimmune crosstalk in autoimmune thyroid diseases.BMC medicine · 2026Article
- Dopamine modulation of aggression.Psychopharmacology · 2026Review
- Frontal Brain Injury Reduces Sensitivity to Reward-Predictive Cues and Remodels the Nucleus Accumbens.bioRxiv : the preprint server for biology · 2026Article
- Incubation of oxycodone craving is associated with CP-AMPAR upregulation in D1 and A2a receptor-expressing medium spiny neurons in nucleus accumbens core and shell.Neuropharmacology · 2026Article
- Cue-Dependent Fear Learning Drives Nucleus Accumbens Spine Plasticity.bioRxiv : the preprint server for biology · 2026Article
- Identification of DARPP-32 as a novel sleep regulator in physiological conditions and experimental Parkinsonism.iScience · 2026Article
- Acute fentanyl and xylazine co-exposure uniquely increase the excitability of dopamine type 2 receptor-expressing striatal medium spiny neurons.Journal of neurophysiology · 2026Article
- Accumbal calcium-permeable AMPA receptors orchestrate neuronal ensembles underlying social attachment.Nature communications · 2026Article
- Nucleus accumbens DRD2 receptor agonism attenuates escape behavior.Frontiers in neuroscience · 2026Article
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
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Authors and funding
18 authors.
Jennifer E ZachryDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Munir Gunes KutluDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Hye Jean YoonDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Michael Z LeonardDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Maxime ChevéeDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Dev D PatelDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Anthony GaidiciDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Veronika KondevDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Kimberly C ThibeaultDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Rishik BethiDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Jennifer TatDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Patrick R MeluginDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Atagun U IsiktasDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA; Department of Neuroscience, Yale University, New Haven, CT 06520, USA.
Max E JoffeDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Denise J CaiNash Family Department of Neuroscience, Icahn School of Medicine, Mount Sinai, New York, NY 10029, USA.
P Jeffrey ConnDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA.
Brad A GrueterDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Erin S CalipariDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: erin.calipari@vanderbilt.edu.
Funding
TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007628 · NIGMS · VANDERBILT UNIVERSITY · PI BARNETT, JOEY VICTOR, KAVALALI, EGE T · 1985 to 2022
$11.2MOverall: Eunice Kennedy Shriver Intellectual and Developmental Disabilities Research Center at VanderbiltP50HD103537 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Lea K Davis · 2020 to 2026
$10.3MInstitutional Career Development CoreKL2TR002245 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Julie A. Bastarache · 2017 to 2026
$9.3MProgram in NeurogenomicsT32MH065215 · NIMH · VANDERBILT UNIVERSITY · PI ROGER J COLBRAN · 2002 to 2026
$6.4MMechanisms of dopaminergic dysfunction in substance use disorderR01DA052317 · NIDA · VANDERBILT UNIVERSITY · PI CALIPARI, ERIN · 2021 to 2025
$2.4MMaking and breaking opioid memories to prevent relapseDP1DA048931 · NIDA · VANDERBILT UNIVERSITY · PI CALIPARI, ERIN · 2019 to 2023
$2.4MCircuit control of motivation to take and seek alcoholR01AA030931 · NIAAA · VANDERBILT UNIVERSITY · PI Erin Calipari · 2023 to 2026
$2.3MDefining the Role of D1 and D2 Medium Spiny Neurons in Relapse to Cocaine SeekingR00DA042111 · NIDA · VANDERBILT UNIVERSITY · PI CALIPARI, ERIN · 2018 to 2020
$747kTraining Program in Social Neuroscience ResearchT32MH135853 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Hirofumi Morishita, SCOTT JAMES RUSSO · 2024 to 2026
$684kPredicting maladaptive aversive learning via computational modeling of insular single cell ensemble activity patternsR21MH132052 · NIMH · VANDERBILT UNIVERSITY · PI KUTLU, MUNIR GUNES · 2023 to 2024
$436kNCATS NIH HHS KL2 TR002245NIAAA NIH HHS R01 AA030931NICHD NIH HHS P50 HD103537NIDA NIH HHS DP1 DA048931NIDA NIH HHS R00 DA042111NIDA NIH HHS R01 DA052317NIGMS NIH HHS T32 GM007628NIMH NIH HHS R21 MH132052NIMH NIH HHS T32 MH065215NIMH NIH HHS T32 MH135853
Abstract
At the core of value-based learning is the nucleus accumbens (NAc). D1- and D2-receptor-containing medium spiny neurons (MSNs) in the NAc core are hypothesized to have opposing valence-based roles in behavior. Using optical imaging and manipulation approaches in mice, we show that neither D1 nor D2 MSNs signal valence. D1 MSN responses were evoked by stimuli regardless of valence or contingency. D2 MSNs were evoked by both cues and outcomes, were dynamically changed with learning, and tracked valence-free prediction error at the population and individual neuron level. Finally, D2 MSN responses to cues were necessary for associative learning. Thus, D1 and D2 MSNs work in tandem, rather than in opposition, by signaling specific properties of stimuli to control learning.
Indexed as
Medium Spiny NeuronsReceptors, Dopamine D1AnimalsMiceMice, Inbred C57BLMice, TransgenicNeuronsNucleus AccumbensReceptors, Dopamine D1aversioncalcium imagingfear conditioningmotivationreinforcement learningstriatum
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.