Journal article
Synchronized firing of fast-spiking interneurons is critical to maintain balanced firing between direct and indirect pathway neurons of the striatum
Journal of neurophysiology, Vol.111(4), pp.836-848
02/15/2014
DOI: 10.1152/jn.00382.2013
PMCID: PMC3921391
PMID: 24304860
Abstract
The inhibitory circuits of the striatum are known to be critical for motor function, yet their contributions to Parkinsonian motor deficits are not clear. Altered firing in the globus pallidus suggests that striatal medium spiny neurons (MSN) of the direct (D1 MSN) and indirect pathway (D2 MSN) are imbalanced during dopamine depletion. Both MSN classes receive inhibitory input from each other and from inhibitory interneurons within the striatum, specifically the fast-spiking interneurons (FSI). To investigate the role of inhibition in maintaining striatal balance, we developed a biologically-realistic striatal network model consisting of multicompartmental neuron models: 500 D1 MSNs, 500 D2 MSNs and 49 FSIs. The D1 and D2 MSN models are differentiated based on published experiments of individual channel modulations by dopamine, with D2 MSNs being more excitable than D1 MSNs. Despite this difference in response to current injection, in the network D1 and D2 MSNs fire at similar frequencies in response to excitatory synaptic input. Simulations further reveal that inhibition from FSIs connected by gap junctions is critical to produce balanced firing. Although gap junctions produce only a small increase in synchronization between FSIs, removing these connections resulted in significant firing differences between D1 and D2 MSNs, and balanced firing was restored by providing synchronized cortical input to the FSIs. Together these findings suggest that desynchronization of FSI firing is sufficient to alter balanced firing between D1 and D2 MSNs.
Details
- Title: Subtitle
- Synchronized firing of fast-spiking interneurons is critical to maintain balanced firing between direct and indirect pathway neurons of the striatum
- Creators
- Sriraman Damodaran - George Mason UniversityRebekah C. Evans - George Mason UniversityKim T. Blackwell - George Mason University
- Resource Type
- Journal article
- Publication Details
- Journal of neurophysiology, Vol.111(4), pp.836-848
- DOI
- 10.1152/jn.00382.2013
- PMID
- 24304860
- PMCID
- PMC3921391
- NLM abbreviation
- J Neurophysiol
- ISSN
- 0022-3077
- eISSN
- 1522-1598
- Publisher
- Amer Physiological Soc
- Number of pages
- 13
- Grant note
- 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) N00014-10-1-0198 / Office of Naval Research Grant Multidisciplinary University Research Initiative
- Language
- English
- Date published
- 02/15/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute
- Record Identifier
- 9984446437302771
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