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Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that targets the corticostriatal system and results in progressive deterioration of cognitive, emotional, and motor skills. Although cortical and striatal neurons are widely studied in animal models of HD, there is li...
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Formato: | Texto |
Lenguaje: | English |
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Frontiers Research Foundation
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100808/ https://www.ncbi.nlm.nih.gov/pubmed/21629717 http://dx.doi.org/10.3389/fnsys.2011.00026 |
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author | Miller, Benjamin R. Walker, Adam G. Barton, Scott J. Rebec, George V. |
author_facet | Miller, Benjamin R. Walker, Adam G. Barton, Scott J. Rebec, George V. |
author_sort | Miller, Benjamin R. |
collection | PubMed |
description | Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that targets the corticostriatal system and results in progressive deterioration of cognitive, emotional, and motor skills. Although cortical and striatal neurons are widely studied in animal models of HD, there is little information on neuronal function during expression of the HD behavioral phenotype. To address this knowledge gap, we used chronically implanted micro-wire bundles to record extracellular spikes and local field potentials (LFPs) in truncated (R6/1 and R6/2) and full-length (knock-in, KI) mouse models as well as in transgenic HD rats (tgHD rats) behaving in an open-field arena. Spike activity was recorded in the striatum of all models and in prefrontal cortex (PFC) of R6/2 and KI mice, and in primary motor cortex (M1) of R6/2 mice. We also recorded LFP activity in R6/2 striatum. All HD models exhibited altered neuronal activity relative to wild-type (WT) controls. Although there was no consistent effect on firing rate across models and brain areas, burst firing was reduced in striatum, PFC, and M1 of R6/2 mice, and in striatum of KI mice. Consistent with a decline in bursting, the inter-spike-interval coefficient of variation was reduced in all regions of all models, except PFC of KI mice and striatum of tgHD rats. Among simultaneously recorded neuron pairs, correlated firing was reduced in all brain regions of all models, while coincident bursting, which measures the temporal overlap between bursting pairs, was reduced in striatum of all models as well as in M1 of R6/2s. Preliminary analysis of striatal LFPs revealed aberrant behavior-related oscillations in the delta to theta range and in gamma activity. Collectively, our results indicate that disrupted corticostriatal processing occurs across multiple HD models despite differences in the severity of the behavioral phenotype. Efforts aimed at normalizing corticostriatal activity may hold the key to developing new HD therapeutics. |
format | Text |
id | pubmed-3100808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-31008082011-05-31 Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease Miller, Benjamin R. Walker, Adam G. Barton, Scott J. Rebec, George V. Front Syst Neurosci Neuroscience Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that targets the corticostriatal system and results in progressive deterioration of cognitive, emotional, and motor skills. Although cortical and striatal neurons are widely studied in animal models of HD, there is little information on neuronal function during expression of the HD behavioral phenotype. To address this knowledge gap, we used chronically implanted micro-wire bundles to record extracellular spikes and local field potentials (LFPs) in truncated (R6/1 and R6/2) and full-length (knock-in, KI) mouse models as well as in transgenic HD rats (tgHD rats) behaving in an open-field arena. Spike activity was recorded in the striatum of all models and in prefrontal cortex (PFC) of R6/2 and KI mice, and in primary motor cortex (M1) of R6/2 mice. We also recorded LFP activity in R6/2 striatum. All HD models exhibited altered neuronal activity relative to wild-type (WT) controls. Although there was no consistent effect on firing rate across models and brain areas, burst firing was reduced in striatum, PFC, and M1 of R6/2 mice, and in striatum of KI mice. Consistent with a decline in bursting, the inter-spike-interval coefficient of variation was reduced in all regions of all models, except PFC of KI mice and striatum of tgHD rats. Among simultaneously recorded neuron pairs, correlated firing was reduced in all brain regions of all models, while coincident bursting, which measures the temporal overlap between bursting pairs, was reduced in striatum of all models as well as in M1 of R6/2s. Preliminary analysis of striatal LFPs revealed aberrant behavior-related oscillations in the delta to theta range and in gamma activity. Collectively, our results indicate that disrupted corticostriatal processing occurs across multiple HD models despite differences in the severity of the behavioral phenotype. Efforts aimed at normalizing corticostriatal activity may hold the key to developing new HD therapeutics. Frontiers Research Foundation 2011-05-09 /pmc/articles/PMC3100808/ /pubmed/21629717 http://dx.doi.org/10.3389/fnsys.2011.00026 Text en Copyright © 2011 Miller, Walker, Barton and Rebec. http://www.frontiersin.org/licenseagreement This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with. |
spellingShingle | Neuroscience Miller, Benjamin R. Walker, Adam G. Barton, Scott J. Rebec, George V. Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease |
title | Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease |
title_full | Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease |
title_fullStr | Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease |
title_full_unstemmed | Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease |
title_short | Dysregulated Neuronal Activity Patterns Implicate Corticostriatal Circuit Dysfunction in Multiple Rodent Models of Huntington's Disease |
title_sort | dysregulated neuronal activity patterns implicate corticostriatal circuit dysfunction in multiple rodent models of huntington's disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100808/ https://www.ncbi.nlm.nih.gov/pubmed/21629717 http://dx.doi.org/10.3389/fnsys.2011.00026 |
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