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Neurobiol Aging. 2017 Dec;60:44-56. doi: 10.1016/j.neurobiolaging.2017.07.005. Epub 2017 Jul 20.

Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein.

Author information

1
Institute of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK. Electronic address: F.tamagnini@reading.ac.uk.
2
Institute of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Exeter, UK.
3
King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.

Abstract

The accumulation of cleaved tau fragments in the brain is associated with several tauopathies. For this reason, we recently developed a transgenic mouse that selectively accumulates a C-Terminal 35 kDa human tau fragment (Tau35). These animals develop progressive motor and spatial memory impairment, paralleled by increased hippocampal glycogen synthase kinase 3β activity. In this neurophysiological study, we focused on the CA1 subfield of the hippocampus, a brain area involved in memory encoding. The accumulation of Tau35 results in a significant increase of short-term facilitation of the synaptic response in the theta frequency range (10 Hz), without affecting basal synaptic transmission and long-term synaptic plasticity. Tau35 expression also alters the intrinsic excitability of CA1 pyramidal neurons. Thus, Tau35 presence is associated with increased and decreased excitability at hyperpolarized and depolarized potentials, respectively. These observations are paralleled by a hyperpolarization of the voltage-sensitivity of noninactivating K+ currents. Further investigation is needed to assess the causal link between such functional alterations and the cognitive and motor impairments previously observed in this model.

KEYWORDS:

Alzheimer's disease; Dementia; Hippocampus; Membrane electrical properties; Neuronal excitability; Progressive supranuclear palsy; Synaptic plasticity; Tauopathy

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