Cited by 96Neural and Behavioral Psychology StudiesNeurology and Historical StudiesNeuroscience and Neuropharmacology Research

The Neurobiology of Thought: The Groundbreaking Discoveries of Patricia Goldman-Rakic 1937-2003

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Arnsten, A. F. T.·2013·Cerebral Cortex

Abstract

Patricia S. Goldman-Rakic (1937-2003) transformed the study of the prefrontal cortex (PFC) and the neural basis of mental representation, the basic building block of abstract thought. Her pioneering research first identified the dorsolateral PFC (dlPFC) region essential for spatial working memory, and the extensive circuits of spatial cognition. She discovered the cellular basis of working memory, illuminating the dlPFC microcircuitry underlying spatially tuned, persistent firing, whereby precise information can be held "in mind": persistent firing arises from recurrent excitation within glutamatergic pyramidal cell circuits in deep layer III, while tuning arises from GABAergic lateral inhibition. She was the first to discover that dopamine is essential for dlPFC function, particularly through D1 receptor actions. She applied a host of technical approaches, providing a new paradigm for scientific inquiry. Goldman-Rakic's work has allowed the perplexing complexities of mental illness to begun to be understood at the cellular level, including atrophy of the dlPFC microcircuits subserving mental representation. She correctly predicted that impairments in dlPFC working memory activity would contribute to thought disorder, a cardinal symptom of schizophrenia. Ten years following her death, we look back to see how she inspired an entire field, fundamentally changing our view of cognition and cognitive disorders.

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  • Layer 3 dorsolateral prefrontal cortex microcircuits, built from reciprocal links between excitatory pyramidal cells and parvalbumin-expressing GABAergic interneurons, support working memory through coordinated activity.

    “Working memory requires the synchronized activity of specific microcircuits in layer 3 of the dorsolateral prefrontal cortex (DLFPC) (Arnsten, 2013), consisting of reciprocal connections between excitatory pyramidal cells (PCs) and a subset of GABAergic interneurons that express the calciumbinding protein parvalbumin (PV) (Curley and Lewis, 2012).”

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  1. Rosvold HE Szwarcbart MK Warren JM Akert K Neural structures involved in delayed response performance The frontal granular cortex and behavior 1964 NY McGraw-Hill

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Authors
Arnsten, A. F. T.
Affiliations
Yale University (US)
Corresponding author
Arnsten, A. F. T.
Venue
Cerebral Cortex
Published
2013-08-07
Volume
23
Issue
10
Pages
2269-2281
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
OpenAlex
W2012801655
Cited by
94
References
127
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 11 · 2019: 5 · 2018: 10 · 2017: 10 · 2016: 7 · 2015: 10 · 2014: 4 · 2013: 2
FWCI
4.19
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Cerebral Cortex (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Neurology › Neurology and Historical Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
prefrontal cortex, dorsolateral prefrontal cortex, working memory, spatial working memory, mental representation, persistent firing, recurrent excitation, dopamine, dopamine D1 receptor, schizophrenia, thought disorder, cognitive disorders, history of neuroscience
MeSH terms
Neurobiology, Neurophysiology, United States, History, 20th Century, History, 21st Century

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