Antithetical roles of tau in hippocampal long-term synaptic depression in rats versus mice
4 affiliations
- 1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System
- 2TANZ Centre for Research in Neurodegenerative Diseases, University of Toronto
- 3Neuroscience and Mental Health, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children
- 4The Centre for Phenogenomics
Abstract
Synaptic dysfunction is a primary feature of tauopathies, a group of major neurodegenerative diseases that includes Alzheimer’s disease. However, the normal synaptic functions of tau are poorly understood. Since rats provide advantages over mice for understanding human tau, such as expressing six tau isoforms and showing more robust signs of tau pathology, as well as offering a richer behavioural repertoire, we developed a tau knockout (Mapt KO) rat line. We primarily investigated the impact of tau elimination on long-term synaptic depression (LTD)—a form of synaptic weakening that tau mediates in mice. Low-frequency stimulation of hippocampal Schaffer collateral–CA1 synapses revealed a robust enhancement of LTD in Mapt KO rats relative to WT littermates. In contrast, in interleaved experiments, Mapt KO mice exhibited reduced LTD compared to WT littermates, in line with previous reports. Together, our findings demonstrate a species-dependent role for endogenous tau in regulating hippocampal LTD, promoting it in mice yet constraining it in rats. Therefore, the functions of tau are not necessarily conserved in rodents, underscoring the importance of animal model choice.
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BibTeX
@article{ralph2026antithetical,
title = {{Antithetical roles of tau in hippocampal long-term synaptic depression in rats versus mice}},
author = {Liam T. Ralph and Eric W. Salter and Patrick Tidball and Brian Park and Sun-Lim Choi and Lijia Zhang and Meng Tian and Ashish Kadia and Fuzi Jin and Clarrisa A. Bradley and Paul E. Fraser and Gerold Schmitt-Ulms and Marina Gertsenstein and Lauryl M. J. Nutter and John Georgiou and Graham L. Collingridge},
journal = {Molecular Brain},
year = {2026},
month = oct,
doi = {10.1186/s13041-026-01341-y},
url = {https://doi.org/10.1186/s13041-026-01341-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Antithetical roles of tau in hippocampal long-term synaptic depression in rats versus mice
AU - Liam T. Ralph
AU - Eric W. Salter
AU - Patrick Tidball
AU - Brian Park
AU - Sun-Lim Choi
AU - Lijia Zhang
AU - Meng Tian
AU - Ashish Kadia
AU - Fuzi Jin
AU - Clarrisa A. Bradley
AU - Paul E. Fraser
AU - Gerold Schmitt-Ulms
AU - Marina Gertsenstein
AU - Lauryl M. J. Nutter
AU - John Georgiou
AU - Graham L. Collingridge
PY - 2026
DA - 2026/10/25
JO - Molecular Brain
DO - 10.1186/s13041-026-01341-y
UR - https://doi.org/10.1186/s13041-026-01341-y
AB - Synaptic dysfunction is a primary feature of tauopathies, a group of major neurodegenerative diseases that includes Alzheimer’s disease. However, the normal synaptic functions of tau are poorly understood. Since rats provide advantages over mice for understanding human tau, such as expressing six tau isoforms and showing more robust signs of tau pathology, as well as offering a richer behavioural repertoire, we developed a tau knockout (Mapt KO) rat line. We primarily investigated the impact of tau elimination on long-term synaptic depression (LTD)—a form of synaptic weakening that tau mediates in mice. Low-frequency stimulation of hippocampal Schaffer collateral–CA1 synapses revealed a robust enhancement of LTD in Mapt KO rats relative to WT littermates. In contrast, in interleaved experiments, Mapt KO mice exhibited reduced LTD compared to WT littermates, in line with previous reports. Together, our findings demonstrate a species-dependent role for endogenous tau in regulating hippocampal LTD, promoting it in mice yet constraining it in rats. Therefore, the functions of tau are not necessarily conserved in rodents, underscoring the importance of animal model choice.
SN - 1756-6606
ER -