Pathological tau disrupts ongoing network activity

Area of Science:

• Neuroscience
• Pathology

Background:

• Pathological tau accumulation causes neurodegeneration in tauopathies, including Alzheimer's disease.
• While tau's cellular effects are known, its impact on intact neocortical network function is unclear.

Purpose of the Study:

• To investigate the effects of pathological tau on neocortical network activity in a mouse model of tauopathy.

Main Methods:

• In vivo intracellular and extracellular recordings of neocortical pyramidal cells in rTg4510 mice.
• Analysis of neuronal activity during different arousal states before significant cell death.

Main Results:

• Transgenic mice exhibited slower membrane potential oscillations during sleep and anesthesia.
• Neuronal firing rates were reduced, with altered firing patterns including longer latencies and inter-spike intervals.
• Pathological tau altered state transitions and Down states in membrane potentials.

Conclusions:

• Pathological tau, even in a fraction of neurons, significantly alters neocortical network activity.
• These network-level changes precede widespread cell death and may contribute to cognitive decline in tauopathies.