Desynchronization of fast-spiking interneurons reduces β-band oscillations and imbalance in firing in the dopamine-depleted striatum

Sriraman Damodaran; John R Cressman; Zbigniew Jedrzejewski-Szmek; Kim T Blackwell

doi:10.1523/JNEUROSCI.3490-14.2015

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Desynchronization of fast-spiking interneurons reduces β-band oscillations and imbalance in firing in the dopamine-depleted striatum

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Desynchronization of fast-spiking interneurons reduces β-band oscillations and imbalance in firing in the dopamine-depleted striatum

Sriraman Damodaran, John R Cressman, Zbigniew Jedrzejewski-Szmek and Kim T Blackwell

The Journal of neuroscience, Vol.35(3), pp.1149-1159

01/21/2015

DOI: 10.1523/JNEUROSCI.3490-14.2015

PMCID: PMC4300321

PMID: 25609629

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Abstract

Oscillations in the β-band (8-30 Hz) that emerge in the output nuclei of the basal ganglia during Parkinson's disease, along with an imbalanced activation of the direct and indirect pathways, have been linked to the hypokinetic motor output associated with the disease. Although dopamine depletion causes a change in cellular and network properties in the striatum, it is unclear whether abnormal activity measured in the globus pallidus and substantia nigra pars reticulata is caused by abnormal striatal activity. Here we use a computational network model of medium spiny neurons (MSNs)-fast-spiking interneurons (FSIs), based on data from several mammalian species, and find that robust β-band oscillations and imbalanced firing emerge from implementation of changes to cellular and circuit properties caused by dopamine depletion. These changes include a reduction in connections between MSNs, a doubling of FSI inhibition to D2 MSNs, an increase in D2 MSN dendritic excitability, and a reduction in D2 MSN somatic excitability. The model reveals that the reduced decorrelation between MSNs attributable to weakened lateral inhibition enables the strong influence of synchronous FSIs on MSN firing and oscillations. Weakened lateral inhibition also produces an increased sensitivity of MSN output to cortical correlation, a condition relevant to the parkinsonian striatum. The oscillations of FSIs, in turn, are strongly modulated by fast electrical transmission between FSIs through gap junctions. These results suggest that pharmaceuticals that desynchronize FSI activity may provide a novel treatment for the enhanced β-band oscillations, imbalanced firing, and motor dysfunction in Parkinson's disease.

Action Potentials - physiology

Beta Rhythm - physiology

Computer Simulation

Corpus Striatum - metabolism

Corpus Striatum - physiopathology

Dopamine - metabolism

Interneurons - physiology

Models, Neurological

Neurons - physiology

Parkinson Disease - metabolism

Parkinson Disease - physiopathology

Details

Title: Subtitle: Desynchronization of fast-spiking interneurons reduces β-band oscillations and imbalance in firing in the dopamine-depleted striatum
Creators: Sriraman Damodaran - George Mason University
John R Cressman - George Mason University
Zbigniew Jedrzejewski-Szmek - George Mason University
Kim T Blackwell - George Mason University
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.35(3), pp.1149-1159
DOI: 10.1523/JNEUROSCI.3490-14.2015
PMID: 25609629
PMCID: PMC4300321
NLM abbreviation: J Neurosci
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: R01AA-16022 / NIAAA NIH HHS R01 AA016022 / NIAAA NIH HHS
Language: English
Date published: 01/21/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
Record Identifier: 9984446282902771

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