title: Pathological tau disrupts ongoing network activity.
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 in vivo 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.
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900 Ramat Gan, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Menkes-Caspi
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900 Ramat Gan, Israel.
authors.forename: Hagar G
authors.initials: HG
authors.lastname: Yamin
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900 Ramat Gan, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Kellner
authors.affiliation: Centre for Cognitive and Neural Systems and Euan MacDonald Centre for Motorneurone Disease Research, University of Edinburgh, Edinburgh, EH8 9XD, UK.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Spires-Jones
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900 Ramat Gan, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Cohen
authors.affiliation: Gonda Brain Research Center, Bar-Ilan University, 52900 Ramat Gan, Israel; MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA. Electronic address: sterned@mail.biu.ac.il.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stern
mesh_terms: D000200:Action Potentials; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019579:Neocortex / Q000378:metabolism / Q000503:physiopathology*; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology*; D024801:Tauopathies / Q000378:metabolism / Q000503:physiopathology*; D016875:tau Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016875:tau Proteins