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Author Notes:

Correspondence: eberhard.voit@bme.gatech.edu

ZQ carried out the modeling, analyses and interpretation of results, and manuscript writing.

GWM participated in the design of the work and help to draft the manuscript.

EOV conceived the study, interpreted results, and wrote the manuscript.

All authors have read and approved the manuscript.

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

Subject:

Research Funding:

This work was supported by a grant from the National Institutes of Health (P01-ES016731, G.W.M. PI) and an endowment from the Georgia Research Alliance (E.O.V).

The internal state of medium spiny neurons varies in response to different input signals

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Journal Title:

BMC Systems Biology

Volume:

Volume 4

Publisher:

, Pages 26-26

Type of Work:

Article | Final Publisher PDF

Abstract:

Background Parkinson's disease, schizophrenia, Huntington's chorea and drug addiction are manifestations of malfunctioning neurons within the striatum region at the base of the human forebrain. A key component of these neurons is the protein DARPP-32, which receives and processes various types of dopamine and glutamate inputs and translates them into specific biochemical, cellular, physiological, and behavioral responses. DARPP-32's unique capacity of faithfully converting distinct neurotransmitter signals into appropriate responses is achieved through a complex phosphorylation-dephosphorylation system that evades intuition and predictability. Results To gain deeper insights into the functioning of the DARPP-32 signal transduction system, we developed a dynamic model that is robust and consistent with available clinical, pharmacological, and biological observations. Upon validation, the model was first used to explore how different input signal scenarios are processed by DARPP-32 and translated into distinct static and dynamic responses. Secondly, a comprehensive perturbation analysis identified the specific role of each component on the system's signal transduction ability. Conclusions Our study investigated the effects of various patterns of neurotransmission on signal integration and interpretation by DARPP-32 and showed that the DARPP-32 system has the capability of discerning surprisingly many neurotransmission scenarios. We also screened out potential mechanisms underlying this capability of the DARPP-32 system. This type of insight deepens our understanding of neuronal signal transduction in normal medium spiny neurons, sheds light on neurological disorders associated with the striatum, and might aid the search for intervention targets in neurological diseases and drug addiction.

Copyright information:

©2010 Qi et al; licensee BioMed Central Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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