Attenuated task-responsive representations of hippocampal place cells induced by amyloid-beta accumulation.

Abstract

Alzheimer's disease (AD) is a typical neurodegenerative disease featuring deficits in spatial memory, which relies on spatial representations by hippocampal place cells. Place cells exhibit task-responsive representation to support memory encoding and retrieval processes. Yet, it remains unclear how this task-responsive spatial representation was interrupted under AD pathologies. Here, we employed a delayed match-to-place spatial memory task with associative and predictive memory processes, during which we electrophysiologically recorded hippocampal place cells with multi-tetrode hyperdrives in rats with i.c.v. amyloid/saline injection. We found that the directional selectivity of place cells coding was maintained in the Amyloid group. The firing stability was higher during predictive memory than during associative memory in both groups. However, the spatial specificity was decreased in the Amyloid group during both associative and predictive memory. Importantly, the place cells in the Amyloid group exhibited attenuated task-responsive representations, i.e. lack of spatial over-representations towards the goal zone and a higher representation of the rest zone, especially during the predictive memory stage. These results raise a hypothesis that the disrupted task-responsive representations of place cells could be an underlying mechanism of spatial memory deficits induced by amyloid proteins.