Pathological tau disrupts ongoing network activity

Noa Menkes-Caspi, Hagar G. Yamin, Vered Kellner, Tara L. Spires-Jones, Dana Cohen, Edward A. Stern

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Pathological tau leads to dementia and neurodegeneration in tauopathies, including Alzheimer's disease. It has been shown to disrupt cellular and synaptic functions, yet its effects on the function of the intact neocortical network remain unknown. Using invivo intracellular and extracellular recordings, we measured ongoing activity of neocortical pyramidal cells during various arousal states in the rTg4510 mouse model of tauopathy, prior to significant cell death, when only a fraction of the neurons show pathological tau. In transgenic mice, membrane potential oscillations are slower during slow-wave sleep and under anesthesia. Intracellular recordings revealed that these changes are due to longer Down states and state transitions of membrane potentials. Firing rates of transgenic neurons are reduced, and firing patterns within Up states are altered, with longer latencies and inter-spike intervals. By changing the activity patterns of a subpopulation of affected neurons, pathological tau reduces the activity of the neocortical network.

Original languageEnglish
Pages (from-to)959-966
Number of pages8
JournalNeuron
Volume85
Issue number5
DOIs
StatePublished - 4 Mar 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

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