Simulation of the capacity and precision of working memory in the hypodopaminergic state

RELEVANCE to schizophrenia

T. Okimura, S. Tanaka, Takaki Maeda, M. Kato, Masaru Mimura

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Working memory (WM) impairment has received attention as a behavioral characteristic of schizophrenia. Neurobiological studies have led to the hypothesis that a deficit in dopamine transmission through D1 receptors in the prefrontal cortex (PFC) is associated with WM impairment in schizophrenia. However, empirical approaches that aim to clarify the nature of the impairment and its underlying mechanism are difficult to enact, especially in unmedicated patients. By contrast, computational approaches using biologically plausible models have formed a powerful theoretical framework for the study of WM impairment in schizophrenia. This article attempts to directly connect neurobiological findings to the neuropsychological behaviors present in patients with schizophrenia. Using a biologically plausible prefrontal cortical circuit model, we simulated sustained activity during a simultaneous, multi-target WM task. We subsequently analyzed how dopaminergic modulation via D1 receptor activation alters the capacity and precision of WM and investigated the underlying mechanism. Hypodopaminergic modulation resulted in imprecision and a reduced capacity in WM primarily due to decreased N-methyl-. d-aspartate (NMDA) conductance. Increasing NMDA conductance ameliorated both impairments. These results account for the mechanism that underlies WM impairments in schizophrenia and provide a theoretical basis for combination therapy with antipsychotic drugs and drugs that enhance NMDA receptor function, which is expected to be effective for the treatment of WM impairments in these patients.

Original languageEnglish
Pages (from-to)80-89
Number of pages10
JournalNeuroscience
Volume295
DOIs
Publication statusPublished - 2015 Jun 4

Fingerprint

Short-Term Memory
Schizophrenia
N-Methylaspartate
Prefrontal Cortex
N-Methyl-D-Aspartate Receptors
Aspartic Acid
Antipsychotic Agents
Dopamine
Theoretical Models
Therapeutics
Pharmaceutical Preparations

Keywords

  • Computational
  • Dopamine
  • N-methyl-d-aspartate
  • Persistent activity
  • Prefrontal cortex
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Simulation of the capacity and precision of working memory in the hypodopaminergic state : RELEVANCE to schizophrenia. / Okimura, T.; Tanaka, S.; Maeda, Takaki; Kato, M.; Mimura, Masaru.

In: Neuroscience, Vol. 295, 04.06.2015, p. 80-89.

Research output: Contribution to journalArticle

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