Cortico-Striatal Cross-Frequency Coupling and Gamma Genesis Disruptions in Huntington's Disease Mouse and Computational Models.

Authors:
Sebastien Naze
Sebastien Naze
Aix Marseille Universite
France
James Humble
James Humble
Center for Health System Improvement
Pengsheng Zheng
Pengsheng Zheng
Institute of Systems Engineering
China
Scott Barton
Scott Barton
Indiana University
Claudia Rangel-Barajas
Claudia Rangel-Barajas
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN)
Mexico
George V Rebec
George V Rebec
Indiana University
Bloomington | United States

eNeuro 2018 Nov-Dec;5(6). Epub 2018 Dec 21.

T.J. Watson IBM Research Center, Yorktown Heights, NY 10598.

Abnormal gamma band power across cortex and striatum is an important phenotype of Huntington's disease (HD) in both patients and animal models, but neither the origin nor the functional relevance of this phenotype is well understood. Here, we analyzed local field potential (LFP) activity in freely behaving, symptomatic R6/2 and Q175 mouse models and corresponding wild-type (WT) controls. We focused on periods of quiet rest, which show strong γ activity in HD mice. Simultaneous recording from motor cortex and its target area in dorsal striatum in the R6/2 model revealed exaggerated functional coupling over that observed in WT between the phase of delta frequencies (1-4 Hz) in cortex and striatum and striatal amplitude modulation of low γ frequencies (25-55 Hz; i.e., phase-amplitude coupling, PAC), but no evidence that abnormal cortical activity alone can account for the increase in striatal γ power. Both HD mouse models had stronger coupling of γ amplitude to δ phase and more unimodal phase distributions than their WT counterparts. To assess the possible role of striatal fast-spiking interneurons (FSIs) in these phenomena, we developed a computational model based on additional striatal recordings from Q175 mice. Changes in peak γ frequency and power ratio were readily reproduced by our computational model, accounting for several experimental findings reported in the literature. Our results suggest that HD is characterized by both a reorganization of cortico-striatal drive and specific population changes related to intrastriatal synaptic coupling.

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http://dx.doi.org/10.1523/ENEURO.0210-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325534PMC
March 2019
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