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

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dc.contributor.authorKim, BoHung
dc.contributor.authorHawes, Sarah L.
dc.contributor.authorGillani, Fawad
dc.contributor.authorWallace, Lane J.
dc.contributor.authorBlackwell, Kim T.
dc.date.accessioned2014-09-15T17:48:03Z
dc.date.available2014-09-15T17:48:03Z
dc.date.issued2013-03-14
dc.description.abstractThe 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.sponsorshipThis 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.
dc.identifier.citationKim 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
dc.identifier.otherdoi:10.1371/journal.pcbi.1002953
dc.identifier.urihttps://hdl.handle.net/1920/8818
dc.language.isoen_US
dc.publisherPublic Library of Science
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subjectCalcium signaling
dc.subjectDepolarization
dc.subjectGlutamate
dc.subjectBiochemical simulations
dc.subjectNeuronal dendrites
dc.subjectSimulation and modeling
dc.subjectSynaptic plasticity
dc.subjectVoltage-gated calcium channels
dc.titleSignaling Pathways Involved in Striatal Synaptic Plasticity are Sensitive to Temporal Pattern and Exhibit Spatial Specificity
dc.typeArticle

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