Age-Dependent Degradation of Locomotion Encoding in Huntington's Disease R6/2 Model Mice

Hagar G. Yamin, Noa Menkes-Caspi, Edward A. Stern, Dana Cohen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Huntington's disease (HD) is an inherited fatal neurodegenerative disease, leading to neocortical and striatal atrophy. The commonly studied R6/2 HD transgenic mouse model displays progressive motor and cognitive deficits in parallel to major pathological changes in corticostriatal circuitry. Objective: To study how disease progression influences striatal encoding of movement. Methods: We chronically recorded neuronal activity in the dorsal striatum of R6/2 transgenic (Tg) mice and their age-matched nontransgenic littermate controls (WTs) during novel environment exposure, a paradigm which engages locomotion to explore the novel environment. Results: Exploratory locomotion degraded with age in Tg mice as compared to WTs. We encountered fewer putative medium spiny neurons (MSNs) - striatal projection neurons, and more inhibitory interneurons - putative fast spiking interneurons (FSIs) in Tg mice as compared to WTs. MSNs from Tg mice fired less spikes in bursts without changing their firing rate, while FSIs from these mice had a lower firing rate and more of them were task-responsive as compared to WTs. Additionally, MSNs from Tg mice displayed a reduced ability to encode locomotion across age groups, likely associated with their low prevalence in Tg mice, whereas the encoding of locomotion by FSIs from Tg mice was substantially reduced solely in old Tg mice as compared to WTs. Conclusion: Our findings reveal an age-dependent decay in striatal information processing in transgenic mice. We propose that the ability of FSIs to compensate for the loss of MSNs by processes of recruitment and enhanced task-responsiveness diminishes with disease progression, possibly manifested in the displayed age-dependent degradation of exploratory locomotion.

Original languageEnglish
Pages (from-to)391-404
Number of pages14
JournalJournal of Huntington's disease
Volume10
Issue number3
DOIs
StatePublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 - The authors. Published by IOS Press.

Keywords

  • Basal ganglia
  • electrophysiology
  • locomotion
  • neurons

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