The Effects of NMDA Subunit Composition on Calcium Influx and Spike Timing-Dependent Plasticity in Striatal Medium Spiny Neurons

Rebekah Evans; Teresa Morera-Herreras; Yihui Cui; Kai Du; Tom Sheehan; Jeanette Hellgren Kotaleski; Laurent Venance; Kim Blackwell

doi:10.1371/journal.pcbi.1002493

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The Effects of NMDA Subunit Composition on Calcium Influx and Spike Timing-Dependent Plasticity in Striatal Medium Spiny Neurons

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The Effects of NMDA Subunit Composition on Calcium Influx and Spike Timing-Dependent Plasticity in Striatal Medium Spiny Neurons

Rebekah Evans, Teresa Morera-Herreras, Yihui Cui, Kai Du, Tom Sheehan, Jeanette Hellgren Kotaleski, Laurent Venance and Kim Blackwell

PLoS computational biology, Vol.8(4), pp.e1002493-e1002493

04/01/2012

DOI: 10.1371/journal.pcbi.1002493

PMCID: PMC3334887

PMID: 22536151

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Abstract

Calcium through NMDA receptors (NMDARs) is necessary for the long-term potentiation (LTP) of synaptic strength; however, NMDARs differ in several properties that can influence the amount of calcium influx into the spine. These properties, such as sensitivity to magnesium block and conductance decay kinetics, change the receptor's response to spike timing dependent plasticity (STDP) protocols, and thereby shape synaptic integration and information processing. This study investigates the role of GluN2 subunit differences on spine calcium concentration during several STDP protocols in a model of a striatal medium spiny projection neuron (MSPN). The multi-compartment, multi-channel model exhibits firing frequency, spike width, and latency to first spike similar to current clamp data from mouse dorsal striatum MSPN. We find that NMDAR-mediated calcium is dependent on GluN2 subunit type, action potential timing, duration of somatic depolarization, and number of action potentials. Furthermore, the model demonstrates that in MSPNs, GluN2A and GluN2B control which STDP intervals allow for substantial calcium elevation in spines. The model predicts that blocking GluN2B subunits would modulate the range of intervals that cause long term potentiation. We confirmed this prediction experimentally, demonstrating that blocking GluN2B in the striatum, narrows the range of STDP intervals that cause long term potentiation. This ability of the GluN2 subunit to modulate the shape of the STDP curve could underlie the role that GluN2 subunits play in learning and development.

Life Sciences

Neurobiology

Neurons and Cognition

Details

Title: Subtitle: The Effects of NMDA Subunit Composition on Calcium Influx and Spike Timing-Dependent Plasticity in Striatal Medium Spiny Neurons
Creators: Rebekah Evans - George Mason University
Teresa Morera-Herreras - Centre Interdisciplinaire de Recherche en Biologie
Yihui Cui - Centre Interdisciplinaire de Recherche en Biologie
Kai Du - Karolinska Institutet
Tom Sheehan - George Mason University
Jeanette Hellgren Kotaleski - Karolinska Institutet
Laurent Venance - Centre Interdisciplinaire de Recherche en Biologie
Kim Blackwell - George Mason University
Resource Type: Journal article
Publication Details: PLoS computational biology, Vol.8(4), pp.e1002493-e1002493
DOI: 10.1371/journal.pcbi.1002493
PMID: 22536151
PMCID: PMC3334887
NLM abbreviation: PLoS Comput Biol
ISSN: 1553-734X
eISSN: 1553-7358
Publisher: Public Library of Science
Language: English
Date published: 04/01/2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
Record Identifier: 9984446399202771

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