Motivational Impairment is Accompanied by Corticoaccumbal Dysfunction in the BACHD-Tg5 Rat Model of Huntington's Disease.
Huntington’s disease
corticostriatal
motivation
nucleus accumbens
prefrontal cortex
Journal
Cerebral cortex (New York, N.Y. : 1991)
ISSN: 1460-2199
Titre abrégé: Cereb Cortex
Pays: United States
ID NLM: 9110718
Informations de publication
Date de publication:
17 12 2019
17 12 2019
Historique:
received:
09
06
2018
revised:
19
12
2018
accepted:
14
01
2019
pubmed:
13
2
2019
medline:
21
10
2020
entrez:
13
2
2019
Statut:
ppublish
Résumé
Neuropsychiatric symptoms, such as avolition, apathy, and anhedonia, precede the onset of debilitating motor symptoms in Huntington's disease (HD), and their development may give insight into early disease progression and treatment. However, the neuronal and circuit mechanisms of premanifest HD pathophysiology are not well-understood. Here, using a transgenic rat model expressing the full-length human mutant HD gene, we find early and profound deficits in reward motivation in the absence of gross motor abnormalities. These deficits are accompanied by significant and progressive dysfunction in corticostriatal processing and communication among brain areas critical for reward-driven behavior. Together, our results define early corticostriatal dysfunction as a possible pathogenic contributor to psychiatric disturbances and may help identify potential pharmacotherapeutic targets for the treatment of HD.
Identifiants
pubmed: 30753343
pii: 5308441
doi: 10.1093/cercor/bhz009
pmc: PMC7150618
doi:
Substances chimiques
HTT protein, human
0
Huntingtin Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4763-4774Subventions
Organisme : NIDA NIH HHS
ID : F32 DA043967
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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