Impaired Experience-Dependent Refinement of Place Cells in a Rat Model of Alzheimer's Disease.

Abstract

Hippocampal place cells play an integral role in generating spatial maps. Impaired spatial memory is a characteristic pathology of Alzheimer's disease (AD), yet it remains unclear how AD influences the properties of hippocampal place cells. To record electrophysiological activity in hippocampal CA1 neurons in freely-moving 18-month-old male TgF344-AD and age-matched wild-type (WT) littermates to examine place cell properties. We implanted 32-channel electrode arrays into the CA1 subfield of 18-month-old male WT and TgF344-AD (n = 6/group) rats. Ten days after implantation, single unit activity in an open field arena was recorded across days. The spatial information content, in-field firing rate, and stability of each place cell was compared across groups. Pathology was assessed by immunohistochemical staining, and a deep neural network approach was used to count cell profiles. Aged TgF344-AD rats exhibited hippocampal amyloid-β deposition, and a significant increase in Iba1 immunoreactivity and microglia cell counts. Place cells from WT and TgF344-AD rat showed equivalent spatial information, in-field firing rates, and place field stability when initially exposed to the arena. However, by day 3, the place cells in aged WT rats showed characteristic spatial tuning as evidenced by higher spatial information content, stability, and in-field firing rates, an effect not seen in TgF344-AD rats. These findings support the notion that altered electrophysiological properties of place cells may contribute to the learning and memory deficits observed in AD.