The utilisation of operant delayed matching and non-matching to position for probing cognitive flexibility and working memory in mouse models of Huntington's disease

Abstract

HighlightsWe compared delayed matching and non-matching to position (DMTP and DNMTP) tasks in two different operant apparatus, the 9-hole operant apparatus configuration and the Skinner-like operant apparatus configuration.We determined that the DMTP and DNMTP operant tasks produce more efficient, robust and reliable results in the Skinner-like operant apparatus configuration.We therefore used the Skinner-like operant apparatus configuration to test DMTP and DNMTP tasks in the HdhQ111 mouse model of HD.We tested the DMTP and DNMTP tasks in the HdhQ111 knock-in mouse model of HD which revealed significant deficits in task acquisition and reversal learning in comparison to wildtype animals.

Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+model of Huntington’s disease

“…Recent work with q175 HD knock-in mice suggests they present subtle motivational alterations detected using mixed fixed-/progressive-ratio operant tasks 43 . Similarly, reduced executive function has been observed in Htt Q111/+ mice using delayed nonmatch to sample tasks 42 . The data presented here ( Figure 6) suggest that 9 month old Htt Q111/+ mice do not have enhanced anxiety or depression-like behaviors, but do show motivational deficits, most notably a reduced performance on a fixed-ratio 1 task, despite normal hedonic drive for sweet stimuli at this time point.…”

A Longitudinal Operant Assessment of Cognitive and Behavioural Changes in the HdhQ111 Mouse Model of Huntington’s Disease

“…Cognitive and behavioural changes such as these have been shown to significantly affect the daily activities of people living with HD, often reducing independence, causing isolation, increasing disability and reducing quality of life [ 10 – 12 ]. A range of knock-in mouse models of HD, have demonstrated cognitive and behavioural changes, these include specific deficits in; motivation, attention, extra dimensional set-shifting, working memory and reversal learning [ 13 – 26 ]. Therefore, cognitive and behavioural changes are a core early symptom of HD, that are present in many of the HD mouse lines.…”

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

“…Further, fornix lesions have been found to result in delay-dependent impairments [39,40], while lesions to the prefrontal cortex and hippocampus have been found to produce a general drop in success rate [28,29]. The latter kind of phenotype was also found in a recent study of the performance of an HD knock-in mouse in a slightly different version of the test [41]. As noted though, these phenotypes do not appear to be directly comparable to the apparent biphasic curves found in the current study.…”