Pathological Tau Disrupts Ongoing Network Activity

• Published in: Neuron (Cambridge, Mass.) Vol. 85; no. 5; pp. 959 - 966
• Main Authors: Menkes-Caspi, Noa, Yamin, Hagar G., Kellner, Vered, Spires-Jones, Tara L., Cohen, Dana, Stern, Edward A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.03.2015; Elsevier Limited
• Subjects: Action Potentials; Age; Alzheimer's disease; Animal cognition; Animals; Apoptosis; Female; Humans; Male; Mice; Mice, Transgenic; Morphology; Neocortex - metabolism; Neocortex - physiopathology; Nerve Net - metabolism; Nerve Net - physiopathology; Neurodegeneration; Neurons; Neuropathology; Rodents; tau Proteins - biosynthesis; tau Proteins - genetics; Tauopathies - metabolism; Tauopathies - physiopathology; Transgenic animals
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.01.025

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. •Pathological tau disrupts the activity of single cells and neocortical networks•Pathological tau alters neocortical neuronal oscillatory patterns•Pathological tau affects firing patterns of neocortical pyramidal cells Menkes-Caspi et al. show that the activity of cortical neurons is reduced in tau-transgenic mice, including in neurons without detectable pathological tau. The pathological effects on a group of neurons are amplified and propagated through the entire cortical network.