Universität zu Köln

Zlebnik, Natalie E., Gildish, Iness, Sesia, Thibaut ORCID: 0000-0003-1761-4458, Fitoussi, Aurelie, Cole, Ellen A., Carson, Brian P., Cachope, Roger and Cheer, Joseph F. (2019). Motivational Impairment is Accompanied by Corticoaccumbal Dysfunction in the BACHD-Tg5 Rat Model of Huntington's Disease. Cereb. Cortex, 29 (11). S. 4763 - 4775. CARY: OXFORD UNIV PRESS INC. ISSN 1460-2199

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zlebnik, Natalie E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gildish, Iness UNSPECIFIED UNSPECIFIED UNSPECIFIED Sesia, Thibaut UNSPECIFIED orcid.org/0000-0003-1761-4458 UNSPECIFIED Fitoussi, Aurelie UNSPECIFIED UNSPECIFIED UNSPECIFIED Cole, Ellen A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Carson, Brian P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cachope, Roger UNSPECIFIED UNSPECIFIED UNSPECIFIED Cheer, Joseph F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-128548
DOI:	10.1093/cercor/bhz009
Journal or Publication Title:	Cereb. Cortex
Volume:	29
Number:	11
Page Range:	S. 4763 - 4775
Date:	2019
Publisher:	OXFORD UNIV PRESS INC
Place of Publication:	CARY
ISSN:	1460-2199
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; MOUSE MODEL; FUNCTIONAL CONNECTIVITY; CORTICOSTRIATAL PATHWAY; DEPENDENT ALTERATIONS; MUTANT HUNTINGTIN; VENTRAL STRIATUM; APATHY; ATROPHY Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12854