A longitudinal operant assessment of cognitive and behavioural changes in the HdhQ111 mouse model of Huntington's Disease

Yhnell, Emma ORCID: https://orcid.org/0000-0003-3960-5181, Dunnett, Stephen ORCID: https://orcid.org/0000-0003-1826-1578 and Brooks, Simon ORCID: https://orcid.org/0000-0001-9853-6177 2016. A longitudinal operant assessment of cognitive and behavioural changes in the HdhQ111 mouse model of Huntington's Disease. PLoS ONE 11 (10) , e0164072. 10.1371/journal.pone.0164072

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Abstract

Huntington’s disease (HD) is characterised by motor symptoms which are often preceded by cognitive and behavioural changes, that can significantly contribute to disease burden for people living with HD. Numerous knock-in mouse models of HD are currently available for scientific research. However, before their use, they must be behaviourally characterised to determine their suitability in recapitulating the symptoms of the human condition. Thus, we sought to longitudinally characterise the nature, severity and time course of cognitive and behavioural changes observed in HdhQ111 heterozygous knock-in mice.To determine changes in cognition and behaviour an extensive battery of operant tests including: fixed ratio, progressive ratio, the five choice serial reaction time task and the serial implicit learning task, were applied longitudinally to HdhQ111 and wild type mice. The operant test battery was conducted at 6, 12 and 18 months of age. Significant deficits were observed in HdhQ111 animals in comparison to wild type animals in all operant tests indicating altered cognition (attentional and executive function) and motivation. However, the cognitive and behavioural deficits observed were not shown to be progressive over time in the longitudinal testing paradigm that was utilised. The results therefore demonstrate that the HdhQ111 mouse model of HD reflects some features of the cognitive and behavioural changes shown in the human condition of HD. Although, the cognitive and behavioural deficits demonstrated were not shown to be progressive over time.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Uncontrolled Keywords:	Animal behavior; Learning; Nose; Mouse models; Animal cognition; Huntington disease; Behavior
Publisher:	Public Library of Science
ISSN:	1932-6203
Funders:	MRC
Date of First Compliant Deposit:	5 October 2016
Date of Acceptance:	19 September 2016
Last Modified:	11 Oct 2023 19:35
URI:	https://orca.cardiff.ac.uk/id/eprint/95130

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