Alterations in hippocampal learning, memory and synaptic plasticity in different mutant tau mouse lines

摘要

Hyperphosphorylation of microtubulin-associated protein tau results in neurofibrillary tangles in central neurones, which may relate to the onset of memory impairment in Alzheimer’s disease (AD). We have compared several mutant tau mouse lines (from strains established by Bue´e et al. & Mandelkow et al.) to investigate whether AD-like tau neuropathology leads to impairments in hippocampus-dependent learning and memory and hippocampal synaptic plasticity. In all of the mutant tau lines used here, hyperphosphorylated tau was found throughout the central nervous system, but especially in limbic structures. These neuropathological alterations were accompanied by distinctly impaired learning and memory in various hippocampus-dependent complex tasks. These impairments could, however, be reversed by switching off the mutant tau transgene in inducible models. Furthermore, we observed impaired long-term depression of hippocampal synaptic transmission in tau mutant brain slices using a novel synaptic plasticity paradigm. These experiments indicate that mutant tau mice can be used to study the neural and behavioural effects of tau pathology and possible treatment.