The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Destruction and Creation of Spatial Tuning by Disinhibition: GABAABlockade of Prefrontal Cortical Neurons Engaged by Working Memory
Open accessAbstract
Local circuit neurons in the dorsolateral prefrontal cortex (dPFC) of monkeys have been implicated in the cellular basis of working memory. To further elucidate the role of inhibition in spatial tuning, we iontophoresed bicuculline methiodide (BMI) onto functionally characterized neurons in the dPFC of monkeys performing an oculomotor delayed response task. This GABA A blockade revealed that both putative interneurons and pyramidal cells possess significant inhibitory tone in the awake, behaving monkey. In addition, BMI application primarily resulted in the loss of previously extant spatial tuning in both cell types through reduction of both isodirectional and cross-directional inhibition. This tuning loss occurred in both the sensorimotor and mnemonic phases of the task, although the delay activity of prefrontal neurons appeared to be particularly affected. Finally, application of BMI also created significant spatial tuning in a sizable minority of units that were untuned in the control condition. Visual field analysis of such tuning suggests that it is likely caused by the unmasking of normally suppressed spatially tuned excitatory input. These findings provide the first direct evidence of directional inhibitory modulation of pyramidal cell and interneuron firing in both the mnemonic and sensorimotor phases of the working memory process, and they implicate a further role for GABAergic interneurons in the construction of spatial tuning in prefrontal cortex.
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“Primate electrophysiological studies show that persistent firing of prefrontal pyramidal cells supports robust and stable WM representations (Funahashi et al. 1989) that depend critically on E/I balance (Rao et al. 2000).”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Rao et al. 2000
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Metadata
- Authors
- Rao, S. G., Williams, G. V., & Goldman-Rakic, P. S.
- Affiliations
- Yale University (US)
- ORCID
- Williams, Graham V.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-01-01
- Volume
- 20
- Issue
- 1
- Pages
- 485-494
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6774140
- OpenAlex
- W2170328434
- Cited by
- 407
- References
- 46
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 29 · 2023: 6 · 2022: 9 · 2021: 14 · 2020: 6 · 2019: 10 · 2018: 11 · 2017: 19 · 2016: 12 · 2015: 18 · 2014: 23 · 2013: 15 · 2012: 20
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (P50 MH44866, R37 MH-3854, P50MH044866)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- spatial tuning, GABAergic inhibition, disinhibition, dorsolateral prefrontal cortex, working memory, bicuculline methiodide, interneurons, pyramidal neurons, delay activity, visual field testing
- MeSH terms
- Action Potentials, Animals, Bicuculline, Fixation, Ocular, Inhibition, Psychological, Interneurons, Macaca mulatta, Memory, Reaction Time, Receptors, GABA-A, Space Perception, Prefrontal Cortex, GABA Antagonists, GABA-A Receptor Antagonists
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