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Author Notes:

Corresponding Author: 950 Atlantic Drive NW, Department of Biomedical Engineering, Atlanta, GA 30332-2000, Tel: 404-385-4761, Fax: 404-894-4243, zhen.qi@gatech.edu

Z.Q., F.T., and E.O.V. designed the study; Z.Q. and G.P.Y. performed the computational research and analyzed the results; Z.Q. and E.O.V. wrote the paper; F.T., O.P., and A.A.G. provided expertise and feedback.

All authors critically reviewed the content and approved the final version for publication.

Any opinions, findings, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsoring institutions.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This work was supported in part by grants from the National Institutes of Health (P01-ES016731, GWM, PI; R01HL095479) and an endowment from the Georgia Research Alliance (EOV, PI).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Biophysics
  • Interaction matrix
  • Mesoscopic model
  • Mobile
  • Neurotransmitter
  • Schizophrenia
  • Systems biology
  • Working memory deficit
  • SUBTHALAMIC NUCLEUS ACTIVITY
  • PRIMATE PREFRONTAL CORTEX
  • VENTRAL TEGMENTAL AREA
  • IN-VIVO
  • BASAL GANGLIA
  • RAT-BRAIN
  • NEUROTRANSMITTER INTERACTIONS
  • GLUTAMATERGIC TRANSMISSION
  • NETWORK CONNECTIVITY
  • INHIBITORY NEURONS

A heuristic model for working memory deficit in schizophrenia

Tools:

Journal Title:

Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids

Volume:

Volume 1860, Number 11, Part B

Publisher:

, Pages 2696-2705

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background The life of schizophrenia patients is severely affected by deficits in working memory. In various brain regions, the reciprocal interactions between excitatory glutamatergic neurons and inhibitory GABAergic neurons are crucial. Other neurotransmitters, in particular dopamine, serotonin, acetylcholine, and norepinephrine, modulate the local balance between glutamate and GABA and therefore regulate the function of brain regions. Persistent alterations in the balances between the neurotransmitters can result in working memory deficits. Methods Here we present a heuristic computational model that accounts for interactions among neurotransmitters across various brain regions. The model is based on the concept of a neurochemical interaction matrix at the biochemical level and combines this matrix with a mobile model representing physiological dynamic balances among neurotransmitter systems associated with working memory. Results The comparison of clinical and simulation results demonstrates that the model output is qualitatively very consistent with the available data. In addition, the model captured how perturbations migrated through different neurotransmitters and brain regions. Results showed that chronic administration of ketamine can cause a variety of imbalances, and application of an antagonist of the D 2 receptor in PFC can also induce imbalances but in a very different manner. Conclusions The heuristic computational model permits a variety of assessments of genetic, biochemical, and pharmacological perturbations and serves as an intuitive tool for explaining clinical and biological observations. General significance The heuristic model is more intuitive than biophysically detailed models. It can serve as an important tool for interdisciplinary communication and even for psychiatric education of patients and relatives.

Copyright information:

© 2016 Elsevier B.V. All rights reserved.

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