Deficits in a Simple Visual Go/No-go Discrimination Task in Two Mouse Models of Huntington's Disease

Area of Science:

• Neuroscience
• Genetics
• Cognitive Science

Background:

• Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansion in the HTT gene.
• Cognitive dysfunction, particularly executive function deficits, is a hallmark of HD.
• Early detection of cognitive impairment is crucial for understanding HD progression and testing interventions.

Purpose of the Study:

• To assess executive function deficits in mouse models of Huntington's disease.
• To evaluate a modified Go/No-go successive discrimination task for its sensitivity to early cognitive impairments in HD.
• To determine if observed deficits are related to motor dysfunction or specific executive function impairments.

Main Methods:

• Utilized two mouse models of Huntington's disease: zQ175 KI and R6/2.
• Administered a modified Go/No-go successive discrimination task to assess response control.
• Analyzed performance for deficits in inhibition and attention, distinguishing from motor impairments.

Main Results:

• Both zQ175 KI and R6/2 mouse models exhibited significant and early deficits in the discrimination task.
• Deficits were observed from 28 weeks in zQ175 KI mice and 9 weeks in R6/2 mice.
• The deficits were attributed to impaired behavioral inhibition and attentional processes, not gross motor dysfunction.

Conclusions:

• The modified Go/No-go discrimination assay effectively detects early cognitive deficits in HD mouse models.
• This assay measures deficits in behavioral inhibition and attention, key aspects of executive function disrupted in HD.
• The task provides a valuable platform for preclinical screening and evaluation of potential Huntington's disease therapies.