Impaired speed encoding and grid cell periodicity in a mouse model of tauopathy.

Dementia is associated with severe spatial memory deficits which arise from dysfunction in hippocampal and parahippocampal circuits. For spatially sensitive neurons, such as grid cells, to faithfully represent the environment these circuits require precise encoding of direction and velocity information. Here, we have probed the firing rate coding properties of neurons in medial entorhinal cortex (MEC) in a mouse model of tauopathy. We find that grid cell firing patterns are largely absent in rTg4510 mice, while head-direction tuning remains largely intact. Conversely, neural representation of running speed information was significantly disturbed, with smaller proportions of MEC cells having firing rates correlated with locomotion in rTg4510 mice. Additionally, the power of local field potential oscillations in the theta and gamma frequency bands, which in wild-type mice are tightly linked to running speed, was invariant in rTg4510 mice during locomotion. These deficits in locomotor speed encoding likely severely impact path integration systems in dementia.