Modeling Intracellular Signaling Underlying Striatal Function in Health and Disease

Anu G. Nair; Omar Gutierrez-Arenas; Olivia Eriksson; Alexandra Jauhiainen; Kim T. Blackwell; Jeanette H. Kotaleski

doi:10.1016/B978-0-12-397897-4.00013-9

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Modeling Intracellular Signaling Underlying Striatal Function in Health and Disease

Book chapter

Open access

Peer reviewed

Modeling Intracellular Signaling Underlying Striatal Function in Health and Disease

Anu G. Nair, Omar Gutierrez-Arenas, Olivia Eriksson, Alexandra Jauhiainen, Kim T. Blackwell and Jeanette H. Kotaleski

Progress in Molecular Biology and Translational Science, pp.277-304

2014

DOI: 10.1016/B978-0-12-397897-4.00013-9

PMCID: PMC4120139

PMID: 24560149

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https://www.ncbi.nlm.nih.gov/pmc/articles/4120139View

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Abstract

Striatum, which is the input nucleus of the basal ganglia, integrates cortical and thalamic glutamatergic inputs with dopaminergic afferents from the substantia nigra pars compacta. The combination of dopamine and glutamate strongly modulates molecular and cellular properties of striatal neurons and the strength of corticostriatal synapses. These actions are performed via intracellular signaling networks, containing several intertwined feedback loops. Understanding the role of dopamine and other neuromodulators requires the development of quantitative dynamical models for describing the intracellular signaling, in order to provide precise unambiguous descriptions and quantitative predictions. Building such models requires integration of data from multiple data sources containing information regarding the molecular interactions, the strength of these interactions, and the subcellular localization of the molecules. Due to the uncertainty, variability, and sparseness of these data, parameter estimation techniques are critical for inferring or constraining the unknown parameters, and sensitivity analysis evaluates which parameters are most critical for a given observed macroscopic behavior. Here, we briefly review the modeling approaches and tools that have been used to investigate biochemical signaling in the striatum, along with some of the models built around striatum. We also suggest a future direction for the development of such models from the, now becoming abundant, high-throughput data.

DARPP32

Dopamine

Kinetic models

LTP

Medium spiny neurons

Neural data integration

Postsynaptic signaling

Striatum

Synaptic plasticity

Details

Title: Subtitle: Modeling Intracellular Signaling Underlying Striatal Function in Health and Disease
Creators: Anu G. Nair - School of Computer Science and Communication, Royal Institute of Technology, Stockholm, Sweden
Omar Gutierrez-Arenas - School of Computer Science and Communication, Royal Institute of Technology, Stockholm, Sweden
Olivia Eriksson - Stockholm University
Alexandra Jauhiainen - Karolinska Institutet
Kim T. Blackwell - George Mason University
Jeanette H. Kotaleski - School of Computer Science and Communication, Royal Institute of Technology, Stockholm, Sweden
Resource Type: Book chapter
Publication Details: Progress in Molecular Biology and Translational Science, pp.277-304
DOI: 10.1016/B978-0-12-397897-4.00013-9
PMID: 24560149
PMCID: PMC4120139
NLM abbreviation: Prog Mol Biol Transl Sci
eISSN: 1878-0814
ISSN: 1877-1173
Language: English
Date published: 2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
Record Identifier: 9984446437902771

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