Selective D2 receptor actions on the functional circuitry of working memory

Wang, Min; Vijayraghavan, Susheel; Goldman-Rakic, Patricia S.

doi:10.1126/science.1091162

Cited by 319Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesNeuroscience and Neuropharmacology Research

Selective D2 receptor actions on the functional circuitry of working memory

Wang, Min, Vijayraghavan, Susheel, Goldman-Rakic, Patricia S.·2004·Science

DOI 10.1126/science.1091162

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Abstract

Prefrontal neurons engaged by working memory tasks express a sequence of phasic and tonic activations linked to a train of sensory, mnemonic, and response-related events. Here, we report that the dopamine D2 receptor selectively modulates the neural activities associated with memory-guided saccades in oculomotor delayed-response tasks yet has little or no effect on the persistent mnemonic-related activity, which is instead modulated by D1 receptors. This associates the D2 receptor with a specific component of working memory circuitry and fractionates the modulatory effects of D1 and D2 receptors on the neural machinery of a cognitive process.

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D2-receptors in the PFC are concentrated in layer V neurons where they increase response-related firing.
“D2-receptors in the PFC are concentrated in layer V neurons where they also increase response-related firing (Wang et al., 2004).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Wang et al., 2004
Excessive D2 receptor stimulation impairs prefrontal cortex working memory function in animals and humans and is associated with increased response-related firing in monkeys and increased response-related blood oxygen level-dependent signals in human imaging studies.
“excessive D2 receptor stimulation impairs PFC working memory function in animals69 and humans70 and is associated with increased response-related firing in monkeys71 and increased response-related blood oxygen level-dependent signals in human imaging studies70.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [71]
Iontophoresis of D2 drugs onto PFC neurons has no effect on delay cell firing during the delay period in a working memory task but has marked effects on response cell firing in relationship to the eye movement response.
“Iontophoresis of D2 drugs onto PFC neurons has no effect on delay cell firing during the delay period in a working memory task but has marked effects on response cell firing in relationship to the eye movement response (124).”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [124]
In contrast to delay cells, layer V sensory-motor response cells in dlPFC show increased firing with high levels of dopamine D2 receptor stimulation.
“In contrast to delay cells, which reduce firing with high levels of dopamine D1R stimulation, layer V sensory-motor response cells in dlPFC show increased firing with high levels of dopamine D2 receptor stimulation63.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [63]

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Authors: Wang, M., Vijayraghavan, S., & Goldman-Rakic, P. S.
Affiliations: Yale University (US)
Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Corresponding author: Wang, Min
ORCID: Wang, Min
Vijayraghavan, Susheel
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2004-02-06
Volume: 303
Issue: 5659
Pages: 853-856
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1091162
OpenAlex: W2002132239
Cited by: 319
References: 29
Citations by year: 2026: 6 · 2025: 3 · 2024: 13 · 2023: 10 · 2022: 9 · 2021: 7 · 2020: 7 · 2019: 10 · 2018: 12 · 2017: 12 · 2016: 15 · 2015: 18 · 2014: 15 · 2013: 19 · 2012: 20
FWCI: 9.39
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (P50 MH44866, P50MH068789, P50MH044866)
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: dopamine D2 receptor, dopamine D1 receptor, working memory, memory-guided saccades, prefrontal cortex, receptor selectivity
MeSH terms: Animals, Benzazepines, Cues, Dose-Response Relationship, Drug, Electrophysiology, Macaca mulatta, Male, Memory, Neurons, Psychomotor Performance, Reward, Saccades, Salicylamides, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, Prefrontal Cortex, Receptors, Dopamine D1, Receptors, Dopamine D2, Dopamine Agonists, Dopamine Antagonists, Quinpirole, Raclopride, Dopamine D2 Receptor Antagonists

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Selective D2 receptor actions on the functional circuitry of working memory

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