Cognitive trajectories in longitudinally trained 3xTg-AD mice

Area of Science:

• Neuroscience
• Cognitive Science
• Animal Models of Disease

Background:

• Preclinical Alzheimer's disease (AD) research often uses cognitively naive animal models.
• Cross-sectional designs may not capture lifespan cognitive changes or human heterogeneity.

Purpose of the Study:

• To investigate the effects of longitudinal cognitive training on cognitive capacities in a well-characterized AD mouse model (3xTg).
• To assess cognitive performance and anxiety-like behaviors across different ages.

Main Methods:

• 3xTg and wild-type mice (n=20) underwent daily Go-No-Go (GNG) operant task training from 3 to 9 months old.
• Cognitive performance (GNG task), anxiety-like behaviors, and long-term recognition memory were assessed at 3, 6, and 9 months.

Main Results:

• GNG training generally improved performance with age across genotypes.
• 3xTg mice showed transient deficits in inhibitory control and signal detection at 3 months, which diminished by 9 months.
• At 9 months, 3xTg mice had comparable long-term recognition memory and anxiety-like behaviors to wild-type mice.

Conclusions:

• Longitudinal cognitive training can normalize cognitive capacities in 3xTg mice, making them comparable to wild-type counterparts.
• This suggests potential functional compensation mechanisms in AD genetic mutation carriers.
• Cognitive training may be a valuable tool for preclinical AD research.