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Molecular mechanisms underlying striatal synaptic plasticity: relevance chronic alcohol consumption and seeking
George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. lackwell, Kim T..ORCID iD: 0000-0003-4711-2344
KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2019 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 49, no 6, p. 768-783Article in journal (Refereed) Published
Abstract [en]

The striatum, the input structure of the basal ganglia, is a major site learning and memory for goal-directed actions and habit formation. iny projection neurons of the striatum integrate cortical, thalamic, d nigral inputs to learn associations, with cortico-striatal synaptic asticity as a learning mechanism. Signaling molecules implicated in naptic plasticity are altered in alcohol withdrawal, which may ntribute to overly strong learning and increased alcohol seeking and nsumption. To understand how interactions among signaling molecules oduce synaptic plasticity, we implemented a mechanistic model of gnaling pathways activated by dopamine D1 receptors, acetylcholine ceptors, and glutamate. We use our novel, computationally efficient mulator, NeuroRD, to simulate stochastic interactions both within and tween dendritic spines. Dopamine release during theta burst and 20-Hz imulation was extrapolated from fast-scan cyclic voltammetry data llected in mouse striatal slices. Our results show that the combined tivity of several key plasticity molecules correctly predicts the currence of either LTP, LTD, or no plasticity for numerous perimental protocols. To investigate spatial interactions, we imulate two spines, either adjacent or separated on a 20-mu m ndritic segment. Our results show that molecules underlying LTP hibit spatial specificity, whereas 2-arachidonoylglycerol exhibits a atially diffuse elevation. We also implement changes in NMDA ceptors, adenylyl cyclase, and G protein signaling that have been asured following chronic alcohol treatment. Simulations under these nditions suggest that the molecular changes can predict changes in naptic plasticity, thereby accounting for some aspects of alcohol use sorder.

Place, publisher, year, edition, pages
Wiley , 2019. Vol. 49, no 6, p. 768-783
Keywords [en]
basal ganglia, computational model, long-term depression, long-term potentiation, signaling pathways, striatum
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:kth:diva-248357DOI: 10.1111/ejn.13919ISI: 000461876600003PubMedID: 29602186Scopus ID: 2-s2.0-85051146502OAI: oai:DiVA.org:kth-248357DiVA, id: diva2:1302688
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QC 20190405

Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-05Bibliographically approved

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Tewatia, ParulHellgren Kotaleski, Jeanette

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