Journal article
Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking
The European journal of neuroscience, Vol.49(6), pp.768-783
03/2019
DOI: 10.1111/ejn.13919
PMCID: PMC6165719
PMID: 29602186
Abstract
The striatum, the input structure of the basal ganglia, is a major site of learning and memory for goal-directed actions and habit formation. Spiny projection neurons of the striatum integrate cortical, thalamic, and nigral inputs to learn associations, with cortico-striatal synaptic plasticity as a learning mechanism. Signaling molecules implicated in synaptic plasticity are altered in alcohol withdrawal, which may contribute to overly strong learning and increased alcohol seeking and consumption. To understand how interactions among signaling molecules produce synaptic plasticity, we implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate. We use our novel, computationally efficient simulator, NeuroRD, to simulate stochastic interactions both within and between dendritic spines. Dopamine release during theta burst and 20-Hz stimulation was extrapolated from fast-scan cyclic voltammetry data collected in mouse striatal slices. Our results show that the combined activity of several key plasticity molecules correctly predicts the occurrence of either LTP, LTD, or no plasticity for numerous experimental protocols. To investigate spatial interactions, we stimulate two spines, either adjacent or separated on a 20-mu m dendritic segment. Our results show that molecules underlying LTP exhibit spatial specificity, whereas 2-arachidonoylglycerol exhibits a spatially diffuse elevation. We also implement changes in NMDA receptors, adenylyl cyclase, and G protein signaling that have been measured following chronic alcohol treatment. Simulations under these conditions suggest that the molecular changes can predict changes in synaptic plasticity, thereby accounting for some aspects of alcohol use disorder.
Details
- Title: Subtitle
- Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking
- Creators
- Kim T. Blackwell - George Mason UniversityArmando G. Salinas - National Institute on Alcohol Abuse and AlcoholismParul Tewatia - KTH Royal Institute of TechnologyBrad English - George Mason UniversityJeanette Hellgren Kotaleski - KTH Royal Institute of TechnologyDavid M. Lovinger - National Institute on Alcohol Abuse and Alcoholism
- Resource Type
- Journal article
- Publication Details
- The European journal of neuroscience, Vol.49(6), pp.768-783
- DOI
- 10.1111/ejn.13919
- PMID
- 29602186
- PMCID
- PMC6165719
- NLM abbreviation
- Eur J Neurosci
- ISSN
- 0953-816X
- eISSN
- 1460-9568
- Publisher
- Wiley
- Number of pages
- 16
- Grant note
- 720270 / European Horizon 2020 Framework Programme R01AA16020 / NIH-NSF CRCNS program through NIAAA Swedish e-Science Research Center N00014-13-1-0745 / ONR grant DURIP ZIAAA000416 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) Swedish Research Council
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
- Record Identifier
- 9984446527802771
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