The Neurobiology of Thought: The Groundbreaking Discoveries of Patricia Goldman-Rakic 1937-2003
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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).”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Arnsten, 2013
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- Authors
- Arnsten, A. F. T.
- Affiliations
- Yale University (US)
- Corresponding author
- Arnsten, A. F. T.
- ORCID
- Arnsten, A. F. T.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-08-07
- Volume
- 23
- Issue
- 10
- Pages
- 2269-2281
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC3767966
- 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
- hybrid
- doi.org
- 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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