Attenuated heterogeneity of hippocampal neuron subsets in response to novelty induced by amyloid-β.

Abstract

Alzheimer's disease (AD) patients exhibited episodic memory impairments including location-object recognition in a spatial environment, which was also presented in animal models with amyloid-β (Aβ) accumulation. A potential cellular mechanism was the unstable representation of spatial information and lack of discrimination ability of novel stimulus in the hippocampal place cells. However, how the firing characteristics of different hippocampal subsets responding to diverse spatial information were interrupted by Aβ accumulation remains unclear. In this study, we observed impaired novel object-location recognition in Aβ-treated Long-Evans rats, with larger receptive fields of place cells in hippocampal CA1, compared with those in the saline-treated group. We identified two subsets of place cells coding object information (ObjCell) and global environment (EnvCell) during the task, with firing heterogeneity in response to introduced novel information. ObjCells displayed a dynamic representation responding to the introduction of novel information, while EnvCells exhibited a stable representation to support the recognition of the familiar environment. However, the dynamic firing patterns of these two subsets of cells were disrupted to present attenuated heterogeneity under Aβ accumulation. The impaired spatial representation novelty information could be due to the disturbed gamma modulation of neural activities. Taken together, these findings provide new evidence for novelty recognition impairments of AD rats with spatial representation dysfunctions of hippocampal subsets.