IMPAIRED NEURAL CODE OF SPATIAL INFORMATION IN A MOUSE MODEL OF TAU PATHOLOGY

Abstract

Dementias are associated with severe spatial memory deficits which likely arises due to dysfunction in hippocampal and parahippocampal circuits. These circuits rely on precise encoding of directional and velocity information for spatially-sensitive neurons, such as grid cells in the medial entorhinal cortex (mEC), to faithfully represent the environment. In this study we examined the impact of tau pathology on the spatial coding properties of neurons in the mEC, using a well-studied transgenic mouse model of tauopathy, the rTg4510 mouse. We have used high density silicon probe electrode arrays to examine the local field potential (LFP) and firing rate coding properties of mEC neurons in male rTg4510 mice (7-8 month old), a mouse model of tauopathy which displays severe spatial memory deficits. Grid cell firing patterns were largely absent in rTg4510 mice, suggesting deficiencies in some, or all, of the information required for path integration. Interestingly, we find that head-direction cells, a key component of any path integration system, are largely intact. In contrast, representation of running speed is significantly disturbed in several ways. A significantly smaller proportion of mEC cells from rTg4510 mice display firing rates correlated with locomotion. Of those cells, a much greater proportion are negatively modulated. Finally, we show large scale changes to neuronal oscillations in rTg4510 mice, which in wildtype animals are tightly linked to running speed. Deficits in locomotor speed encoding are likely to severely impact the ability of animals to continuously update positional information and thus disrupt path integration systems in these mice and in dementia patients.