Effects of altered tau expression on dentate granule cell excitability in mice

Ryan A. Cloyd, John Koren, Jose F. Abisambra, Bret N. Smith

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Tauopathies, including Alzheimer's disease, are characterized by progressive accumulation of hyperphosphorylated and pathologic tau protein in association with onset of cognitive and behavioral impairment. Tau pathology is also associated with increased susceptibility to seizures and epilepsy, with tau−/− mice showing seizure resistance in some epilepsy models. To better understand how tau pathology is related to neuronal excitability, we performed whole-cell patch-clamp electrophysiology in dentate gyrus granule cells of tau−/− and human-tau expressing, htau mice. The htau mouse is unique from other transgenic tau models in that the endogenous murine tau gene has been and replaced with readily phosphorylated human tau. We assessed several measures of neuronal excitability, including evoked action potential frequency and excitatory synaptic responses in dentate granule cells from tau−/−, htau, and non-transgenic control mice at 1.5, 4, and 9 months of age. Compared to age matched controls, dentate granule cells from both tau−/− and htau mice had a lower peak frequency of evoked action potentials and greater paired pulse facilitation, suggesting reduced neuronal excitability. Our results suggest that neuronal excitability is more strongly influenced by the absence of functional tau than by the presence of pathologic tau. These results also suggest that tau's effect on neuronal excitability is more complex than previously understood.

Original languageEnglish
Article number113766
JournalExperimental Neurology
Volume343
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
This work was funded by National Institutes on Health [ NINDS 1R01NS092552 , NINDS 5R01NS091329 , NCATS TL1TR001997 , and NIGMS 1T32GM118292 ] and the Department of Defense [ W81XWH-15-1-0551 ].

Publisher Copyright:
© 2021

Keywords

  • Dentate granule cell
  • EPSC
  • Hippocampus
  • Microtubule associated protein tau
  • Tau
  • Tauopathy
  • htau

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Fingerprint

Dive into the research topics of 'Effects of altered tau expression on dentate granule cell excitability in mice'. Together they form a unique fingerprint.

Cite this