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Early impairment of thalamocortical circuit activity and coherence in a mouse model of Huntington's disease

Title
Early impairment of thalamocortical circuit activity and coherence in a mouse model of Huntington's disease
Authors
Shobe, Justin L.Donzis, Elissa J.Lee, KwangChopra, SamikshaMasmanidis, Sotiris C.Cepeda, CarlosLevine, Michael S.
DGIST Authors
Shobe, Justin L.; Donzis, Elissa J.; Lee, Kwang; Chopra, Samiksha; Masmanidis, Sotiris C.; Cepeda, Carlos; Levine, Michael S.
Issue Date
2021-09
Citation
Neurobiology of Disease, 157, 105447
Type
Article
Author Keywords
Cortical interneuronsHuntington&aposs diseaseMotor cortexQ175 miceThalamocortical projection
Keywords
NERVE-CELL LOSSPROJECTION NEURONSDIFFERENTIAL LOSSPARKINSONSNUCLEUSSYSTEMSCORTEX
ISSN
0969-9961
Abstract
Huntington's disease (HD) is a progressive, fatal neurodegenerative disorder characterized by motor, cognitive, and psychiatric disturbances. There is no known cure for HD, but its progressive nature allows for early therapeutic intervention. Currently, much of the research has focused on the striatum, however, there is evidence suggesting that disruption of thalamocortical circuits could underlie some of the early symptoms of HD. Loss of both cortical pyramidal neurons (CPNs) and thalamic neurons occurs in HD patients, and cognitive, somatosensory, and attention deficits precede motor abnormalities. However, the role of thalamocortical pathways in HD progression has been understudied. Here, we measured single unit activity and local field potentials (LFPs) from electrode arrays implanted in the thalamus and primary motor cortex of 4–5 month-old male and female Q175 mice. We assessed neuronal activity under baseline conditions as well as during presentation of rewards delivered via actuation of an audible solenoid valve. HD mice showed a significantly delayed licking response to the reward stimulus. At the same time, neuronal activation to the reward was delayed in thalamic neurons, CPNs and fast-spiking cortical interneurons (FSIs) of HD mice. In addition, thalamocortical coherence increased at lower frequencies in HD relative to wildtype mice. Together, these data provide evidence that impaired cortical and thalamic responses to reward stimuli, and impaired thalamocortical coherence, may play an important early role in motor, cognitive, and learning deficits in HD patients. ⓒ 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
URI
http://hdl.handle.net/20.500.11750/13872
DOI
10.1016/j.nbd.2021.105447
Publisher
Academic Press
Related Researcher
  • Author Lee, Kwang Neural Dynamics Laboratory
  • Research Interests 신경회로, 신경기록, 신경조절, 신경 모델링, 뇌-기계 인터페이스
Files:
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Collection:
Department of Brain SciencesNeural Dynamics Laboratory1. Journal Articles


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