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Modulation of memory fields by dopamine Dl receptors in prefrontal cortex
Abstract
Dopamine has been implicated in the cognitive process of working memory but the cellular basis of its action has yet to be revealed. By combining iontophoretic analysis of dopamine receptors with single-cell recording during behaviour, we found that D1 antagonists can selectively potentiate the 'memory fields' of prefrontal neurons which subserve working memory. The precision shown for D1 receptor modulation of mnemonic processing indicates a direct gating of selective excitatory synaptic inputs to prefrontal neurons during cognition.
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“evidence from non‐human primates (Sawaguchi & Goldman‐Rakic, 1991, 1994; Williams & Goldmanrakic, 1995) and in healthy humans (Fischer et al., 2010) showed that dopamine depletion or antagonism impairs visuospatial WM.”
From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as Williams & Goldmanrakic, 1995
In the citing paper
“Third, dopamine exerts a significant influence over prefrontal cortical functions such as working memory (Williams and Goldman-Rakic, 1995), in a manner that depends on initial levels or efficacy of this neuromodulator (Cools and D’Esposito, 2011).”
From Goals and Habits in the Brain (2013) · cites this paper as Williams and Goldman-Rakic, 1995
In the citing paper
“Dopaminergic signalling has a role in the top-down regulation of spatial attention, and D1 dopaminergic receptors modulate response amplitude and selectivity in the dorsolateral prefrontal cortex for preferred spatial locations during working memory tasks204,205.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [205]
In the citing paper
“Dopaminergic signalling has a role in the top-down regulation of spatial attention, and D1 dopaminergic receptors modulate response amplitude and selectivity in the dorsolateral prefrontal cortex for preferred spatial locations during working memory tasks204,205.”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [205]
In the citing paper
“It is also consistent with a growing literature documenting baseline performance-dependent effects of stimulants and related drugs, which have been explained by a hypothesized inverted U-shaped function, whereby optimal catecholamine levels determine optimal performance, and levels along the curve at either side of the optimum are associated with impaired performance (Robbins and Sahakian, 1979; N”
From A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment (2013) · cites this paper as Williams and Goldman-Rakic, 1995
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“Blocking prefrontal D1Rs impairs spatial tuning [109], but has been also reported to improve spatial tuning of PFC neurons [110], presumably depending on the baseline tuning strength.”
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“These data are echoed in vivo, where high doses of D1R antagonist lead to loss of dlPFC delay cell firing and to working memory impairment (Williams and Goldman-Rakic, 1995).”
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“…of behavioural studies that DA plays different roles in each projection target; DA in the NAc is required for responding appropriately to reward predictive cues (Yun et al. 2004), whereas DA in the mPFC plays a role in working memory (Williams & Goldman-Rakic, 1995; Chudasama & Robbins, 2004).”
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“We found that if the recurrent network is dominated by inhibition, the effect is the opposite (a reduction of the persistent activity) if the modulation is done locally in a single cell (Fig. 8). If this is true, then local iontophoresis of drugs ( Williams and Goldman-Rakic, 1995 ) that presumably affects only a few…”
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“…improves cognitive function (including working memory) in patients with Parkinson’s disease (Gasparini et al. 1997), while injection of D1 antagonists into the dorsolateral prefrontal cortex impairs tasks that require working memory (Sawaguchi & Goldman-Rakic, 1991; Williams & Goldman-Rakic, 1995).”
BackgroundRoyall, D. R., Lauterbach, E. C., Cummings, J. L., Reeve, A., Rummans, T. A., Kaufer, D., LaFrance, W. C., Jr., & Coffey, C. E. (2002) · Journal of Neuropsychiatry · doi:10.1176/jnp.14.4.377 · Cited by 841
Serotonin modulation of cortical neurons and networks
Celada, P., Puig, M. V., & Artigas, F. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00025 · Cited by 462
“Yet, unlike dopamine, whose function in the PFC has been extensively studied (Williams and Goldman-Rakic, 1995; Robbins and Arnsten, 2009), the role of 5-HT in PFC remains less known than that of dopamine.”
BackgroundSeamans, J. K., Floresco, S., & Phillips, A. G. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-04-01613.1998 · Cited by 480
Widespread origin of the primate mesofrontal dopamine system
Williams, S. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.4.321 · Cited by 479
Opponency revisited: competition and cooperation between dopamine and serotonin
Boureau, Y.-L., & Dayan, P. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.151 · Cited by 456
“Its influence over working memory (Williams and Goldman-Rakic, 1995) famously follows an inverted U-shaped function; too little as well as too much DA impairs performance.”
BackgroundLinking Mind and Brain in the Study of Mental Illnesses: A Project for a Scientific Psychopathology
Andreasen, N. C. (1997) · Science · doi:10.1126/science.275.5306.1586 · Cited by 454
Leon, M. I., & Shadlen, M. N. (1999) · Neuron · doi:10.1016/s0896-6273(00)80854-5 · Cited by 449
Role of the Lateral Prefrontal Cortex in Executive Behavioral Control
Tanji, J., & Hoshi, E. (2008) · Physiological Reviews · doi:10.1152/physrev.00014.2007 · Cited by 477
What, If Anything, Is Rodent Prefrontal Cortex?
Laubach, M., Amarante, L. M., Swanson, K., & White, S. R. (2018) · eNeuro · doi:10.1523/eneuro.0315-18.2018 · Cited by 487
“, 1989) and that the signals were highly sensitive to perturbations of cortical dopamine receptors (Williams and Goldman-Rakic, 1995).”
BackgroundMesocortical dopamine modulation of executive functions: beyond working memory
Floresco, S. B., & Magyar, O. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0404-5 · Cited by 426
“One component is the “online” retention of information over a brief delay period, which may be subserved by firing in local PFC circuits and modulated by D1 receptor activity (Williams and Goldman-Rakic 1995).”
BackgroundInfluentialNeuromodulatory transmitter systems in the cortex and their role in cortical plasticity
Gu, Q. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00026-x · Cited by 518
A role for NMDA-receptor channels in working memory
Lisman, J. E., Fellous, J., & Wang, X. (1998) · Nature Neuroscience · doi:10.1038/1086 · Cited by 438
Metadata
- Authors
- Williams, G. V., & Goldman-Rakic, P. S.
- Affiliations
- Yale University (US)
- ORCID
- Williams, Graham V.
- Venue
- Nature
- Published
- 1995-08
- Volume
- 376
- Issue
- 6541
- Pages
- 572-575
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2084007108
- Cited by
- 1,593
- References
- 42
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 29 · 2023: 26 · 2022: 36 · 2021: 30 · 2020: 27 · 2019: 27 · 2018: 37 · 2017: 33 · 2016: 48 · 2015: 63 · 2014: 45 · 2013: 78 · 2012: 74
- FWCI
- 16.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- dopamine D1 receptor, working memory, prefrontal cortex, memory field, dopamine D1 receptor antagonist, synaptic modulation, excitatory synaptic input, iontophoresis, single-unit recording
- MeSH terms
- Animals, Haplorhini, Dose-Response Relationship, Drug, Iontophoresis, Memory, Neurons, Psychomotor Performance, Prefrontal Cortex, Receptors, Dopamine D1, Receptors, Dopamine D2
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