Journal article
Signaling Pathways Involved in Striatal Synaptic Plasticity are Sensitive to Temporal Pattern and Exhibit Spatial Specificity
PLoS computational biology, Vol.9(3), pp.e1002953-e1002953
03/01/2013
DOI: 10.1371/journal.pcbi.1002953
PMCID: PMC3597530
PMID: 23516346
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.
Details
- Title: Subtitle
- Signaling Pathways Involved in Striatal Synaptic Plasticity are Sensitive to Temporal Pattern and Exhibit Spatial Specificity
- Creators
- BoHung Kim - George Mason UniversitySarah L. Hawes - George Mason UniversityFawad Gillani - George Mason UniversityLane J. Wallace - The Ohio State UniversityKim T. Blackwell - George Mason University
- Resource Type
- Journal article
- Publication Details
- PLoS computational biology, Vol.9(3), pp.e1002953-e1002953
- DOI
- 10.1371/journal.pcbi.1002953
- PMID
- 23516346
- PMCID
- PMC3597530
- NLM abbreviation
- PLoS Comput Biol
- ISSN
- 1553-734X
- eISSN
- 1553-7358
- Publisher
- Public Library Science
- Number of pages
- 16
- Grant note
- MURI N00014-10-1-0198 / ONR grant RO1AA-16022 / joint NIH-NSF CRCNS program through NIAAA grant R01AA016022 / 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) George Mason University Libraries Open Access Publishing Fund
- Language
- English
- Date published
- 03/01/2013
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
- Record Identifier
- 9984446541102771
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