Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic mice

Area of Science:

• Neuroscience
• Pathology
• Genetics

Background:

• Neurofibrillary tangles (NFTs), composed of tau protein aggregates, are a hallmark of Alzheimer's disease (AD) and familial frontotemporal dementia (FTDP-17).
• Transgenic mouse models expressing the FTDP-17-associated P301L tau mutation replicate NFT formation in brain regions affected in AD, such as the hippocampus and amygdala.

Purpose of the Study:

• To investigate the cognitive and behavioral effects of tau pathology in P301L transgenic mice, focusing on hippocampus-dependent functions.
• To assess spatial memory and exploratory behavior in P301L mice at different ages to understand the progression of tau-related deficits.

Main Methods:

• Behavioral testing of P301L transgenic mice and control littermates.
• Assessment of spatial reference and working memory using the Morris water maze and Y-maze.
• Evaluation of exploratory behavior and anxiety using the open field and elevated O-maze.

Main Results:

• P301L mice exhibited intact spatial working memory but significant impairment in spatial reference memory at 6 and 11 months of age.
• A modest disinhibition of exploratory behavior was observed at 6 months, becoming more pronounced with age.
• Previous amygdala-specific tests showed increased exploratory behavior and accelerated extinction of conditioned taste aversion.

Conclusions:

• Tau pathology in P301L mice leads to specific deficits in spatial reference memory, suggesting hippocampal dysfunction.
• The observed behavioral disinhibition and memory impairments in P301L mice provide a valuable model for studying tauopathies like AD and FTDP-17.
• These findings underscore the critical role of tau protein aggregation in cognitive decline and behavioral changes associated with neurodegenerative diseases.