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

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,...

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Autores principales: Tamagnini, Francesco, Walsh, Darren A., Brown, Jon T., Bondulich, Marie K., Hanger, Diane P., Randall, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654728/
https://www.ncbi.nlm.nih.gov/pubmed/28917666
http://dx.doi.org/10.1016/j.neurobiolaging.2017.07.005
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author Tamagnini, Francesco
Walsh, Darren A.
Brown, Jon T.
Bondulich, Marie K.
Hanger, Diane P.
Randall, Andrew D.
author_facet Tamagnini, Francesco
Walsh, Darren A.
Brown, Jon T.
Bondulich, Marie K.
Hanger, Diane P.
Randall, Andrew D.
author_sort Tamagnini, Francesco
collection PubMed
description 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.
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spelling pubmed-56547282017-12-01 Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein Tamagnini, Francesco Walsh, Darren A. Brown, Jon T. Bondulich, Marie K. Hanger, Diane P. Randall, Andrew D. Neurobiol Aging Article 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. Elsevier 2017-12 /pmc/articles/PMC5654728/ /pubmed/28917666 http://dx.doi.org/10.1016/j.neurobiolaging.2017.07.005 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tamagnini, Francesco
Walsh, Darren A.
Brown, Jon T.
Bondulich, Marie K.
Hanger, Diane P.
Randall, Andrew D.
Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein
title Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein
title_full Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein
title_fullStr Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein
title_full_unstemmed Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein
title_short Hippocampal neurophysiology is modified by a disease-associated C-terminal fragment of tau protein
title_sort hippocampal neurophysiology is modified by a disease-associated c-terminal fragment of tau protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654728/
https://www.ncbi.nlm.nih.gov/pubmed/28917666
http://dx.doi.org/10.1016/j.neurobiolaging.2017.07.005
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