Cited by 407Neural dynamics and brain functionNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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Destruction and Creation of Spatial Tuning by Disinhibition: GABAABlockade of Prefrontal Cortical Neurons Engaged by Working Memory

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Rao, Srinivas G., Williams, Graham V., Goldman-Rakic, Patricia S.·2000·The Journal of Neuroscience

DOI 10.1523/jneurosci.20-01-00485.2000PMC PMC6774140

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Abstract

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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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
DOI: 10.1523/jneurosci.20-01-00485.2000
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: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
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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Destruction and Creation of Spatial Tuning by Disinhibition: GABAABlockade of Prefrontal Cortical Neurons Engaged by Working Memory

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