rTg4510 Tauopathy Mice Exhibit Non-Spatial Memory Deficits Prevented by Doxycycline Treatment.

Area of Science:

• Neuroscience
• Neurodegenerative Diseases
• Behavioral Science

Background:

• Hyperphosphorylated tau and neurofibrillary tangles are key in tauopathies like Alzheimer's disease (AD).
• The rTg4510 mouse model exhibits tauopathy without amyloid-β, aiding tau-driven neurodegeneration research.
• Prior studies noted spatial and object-recognition memory deficits in rTg4510 mice, preventable by doxycycline (DOX).

Purpose of the Study:

• To investigate if non-spatial hippocampal learning, particularly temporal associative learning, is affected in rTg4510 mice.
• To assess the impact of mutant human tau (P301L) expression on hippocampus-dependent learning.
• To determine if DOX-mediated suppression of tau expression can prevent these learning deficits.

Main Methods:

• Six-month-old rTg4510 mice with/without DOX treatment were assessed.
• Spontaneous home cage activity was measured to control for motor confounds.
• Hippocampus-dependent non-spatial learning was tested via trace eyeblink conditioning and contextual fear conditioning.

Main Results:

• rTg4510 mice without DOX showed impaired trace eyeblink conditioning acquisition and subtle temporal processing deficits.
• Contextual fear conditioning deficits were milder, with intact general motor function.
• Two months of DOX treatment prevented learning impairments, linking them to tau overexpression.

Conclusions:

• rTg4510 mice display deficits in non-spatial temporal associative learning, complementing spatial and object-recognition impairments.
• Trace eyeblink conditioning is a sensitive assay for tau-related hippocampal dysfunction.
• DOX treatment's efficacy suggests its potential as a biomarker for tau-targeted therapies.