Using Scientifica micromanipulators to investigate consequences of Tau pathology on hippocampal pyramidal neurons and network activity in ageing mice

Summary

We wanted to find out how pathological forms of the human Tau protein (pTau) affect neuronal activity and memory. To do this, we examined THY-Tau22 transgenic mice, a popular tauopathy model. We tracked pTau across the lifetime of the mice, tested hippocampal-dependent memory, and recorded network oscillations, single cells, and populations of cells in aged mice.

We observed that in ageing mice, pTau spread from the axons of pyramidal neurons to oligodendrocytes. The oligodendrocytes are a type of glial cell that insulates axons with myelin.

Transgenic mice were impaired in recognising novelty, but had unimpaired spatial working and reference memory. Hippocampal pyramidal neurons, representing memories, exhibit a wide range of firing rates, and in aged transgenic mice there were significantly fewer high-firing rate pyramidal neurons.

Despite the loss of neurons, network oscillations and the activity of pTau-free neurons within pTau hotspots were surprisingly normal. The results support the hypothesis that unaffected subcortical inputs to the hippocampus maintain the network, largely counteracting the high levels of pTau and neurodegeneration.

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