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Signaling Pathways Involved in Striatal Synaptic Plasticity are Sensitive to Temporal Pattern and Exhibit Spatial Specificity

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dc.contributor.author Kim, BoHung
dc.contributor.author Hawes, Sarah L.
dc.contributor.author Gillani, Fawad
dc.contributor.author Wallace, Lane J.
dc.contributor.author Blackwell, Kim T.
dc.date.accessioned 2014-09-15T17:48:03Z
dc.date.available 2014-09-15T17:48:03Z
dc.date.issued 2013-03-14
dc.identifier.citation Kim B, Hawes SL, Gillani F, Wallace LJ, Blackwell KT (2013) Signaling Pathways Involved in Striatal Synaptic Plasticity are Sensitive to Temporal Pattern and Exhibit Spatial Specificity. PLoS Comput Biol 9(3): e1002953. doi:10.1371/journal.pcbi.1002953 en_US
dc.identifier.other doi:10.1371/journal.pcbi.1002953
dc.identifier.uri https://hdl.handle.net/1920/8818
dc.description.abstract The basal ganglia is a brain region critically involved in reinforcement learning and motor control. Synaptic plasticity in the striatum of the basal ganglia is a cellular mechanism implicated in learning and neuronal information processing. Therefore, understanding how different spatio-temporal patterns of synaptic input select for different types of plasticity is key to understanding learning mechanisms. In striatal medium spiny projection neurons (MSPN), both long term potentiation (LTP) and long term depression (LTD) require an elevation in intracellular calcium concentration; however, it is unknown how the post-synaptic neuron discriminates between different patterns of calcium influx. Using computer modeling, we investigate the hypothesis that temporal pattern of stimulation can select for either endocannabinoid production (for LTD) or protein kinase C (PKC) activation (for LTP) in striatal MSPNs. We implement a stochastic model of the post-synaptic signaling pathways in a dendrite with one or more diffusionally coupled spines. The model is validated by comparison to experiments measuring endocannabinoid-dependent depolarization induced suppression of inhibition. Using the validated model, simulations demonstrate that theta burst stimulation, which produces LTP, increases the activation of PKC as compared to 20 Hz stimulation, which produces LTD. The model prediction that PKC activation is required for theta burst LTP is confirmed experimentally. Using the ratio of PKC to endocannabinoid production as an index of plasticity direction, model simulations demonstrate that LTP exhibits spine level spatial specificity, whereas LTD is more diffuse. These results suggest that spatio-temporal control of striatal information processing employs these Gq coupled pathways.
dc.description.sponsorship This work was supported by ONR grant MURI N00014-10-1-0198 and through the joint NIH-NSF CRCNS program through NIAAA grant RO1AA-16022. Publication of this article was funded in part by the George Mason University Libraries Open Access Publishing Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.rights Attribution 3.0 United States *
dc.rights.uri http://creativecommons.org/licenses/by/3.0/us/ *
dc.subject calcium signaling en_US
dc.subject depolarization en_US
dc.subject glutamate en_US
dc.subject biochemical simulations en_US
dc.subject neuronal dendrites en_US
dc.subject simulation and modeling en_US
dc.subject synaptic plasticity en_US
dc.subject voltage-gated calcium channels en_US
dc.title Signaling Pathways Involved in Striatal Synaptic Plasticity are Sensitive to Temporal Pattern and Exhibit Spatial Specificity en_US
dc.type Article en_US


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