Cited by 313Neurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatmentNeuroscience and Neuropharmacology Research

The Physiological Role of 5-HT2AReceptors in Working Memory

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Williams, Graham V., Rao, Srinivas G., Goldman-Rakic, Patricia S.·2002·The Journal of Neuroscience

Abstract

Dorsolateral prefrontal cortex has an essential role in the cognitive process of working memory, dysfunction of which is considered to be a core deficit in schizophrenia. Although this cortical region is densely innervated with 5-HT 2A receptors to which atypical antipsychotic drugs bind with high affinity, little is known of the influence of this serotonin receptor subtype on prefrontal function. We addressed this issue by examining the effects of iontophoresis of selective receptor ligands on prefrontal neurons possessing spatially tuned delay activity, or “memory fields,” in monkeys performing a delayed-response task. Memory fields of putative pyramidal cells were attenuated by iontophoresis of 5-HT 2A antagonists, which primarily produced a reduction in delay activity for preferred target locations. Conversely, 5-HT 2A stimulation by α-methyl-5-HT or 5-HT itself, accentuated the spatial tuning of these neurons by producing a modest increase in activity for preferred target locations and/or a reduction in activity for nonpreferred locations. The agonist effects could be reversed by the selective antagonist MDL100,907, and were dose-dependent, such that high levels attenuated spatial tuning by profoundly reducing delay activity. A role for feedforward inhibitory circuitry in these effects was supported by the finding that 5-HT 2A blockade also attenuated the memory fields of putative interneurons. We conclude that prefrontal 5-HT 2A receptors have a hitherto unrecognized role in the cognitive function of working memory, which involves actions at both excitatory and inhibitory elements within local circuitry.

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Crossref · 10.1523/jneurosci.22-07-02843.2002

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  • High levels of 5-HT2A receptor stimulation can suppress dorsolateral PFC neuronal firing in monkeys performing a working memory task.

    “one study has shown that high levels of 5-HT2A receptor stimulation can suppress dorsolateral PFC neuronal firing in monkeys performing a working memory task161.”

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Authors
Williams, G. V., Rao, S. G., & Goldman-Rakic, P. S.
Affiliations
Yale University (US)
Venue
The Journal of Neuroscience
Published
2002-04-01
Volume
22
Issue
7
Pages
2843-2854
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1635746382
Cited by
311
References
87
Citations by year
2026: 6 · 2025: 6 · 2024: 13 · 2023: 7 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 10 · 2016: 14 · 2015: 14 · 2014: 13 · 2013: 12 · 2012: 10
FWCI
6.76
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (MH 44866, R37MH038546, P50MH044866)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
5-HT2A receptor, serotonin, working memory, dorsolateral prefrontal cortex, delay activity, memory field, pyramidal neurons, interneurons, feedforward inhibition, schizophrenia, atypical antipsychotics, alpha-methyl-5-HT, spatial tuning, delayed response task, iontophoresis
MeSH terms
Action Potentials, Animals, Cognition, Fixation, Ocular, Iontophoresis, Ligands, Macaca mulatta, Male, Memory, Short-Term, Neurons, Photic Stimulation, Reaction Time, Receptors, Serotonin, Saccades, Serotonin Antagonists, Serotonin Receptor Agonists, Prefrontal Cortex, Pyramidal Cells, Receptor, Serotonin, 5-HT2A

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