Deficit in hippocampal ripples does not preclude spatial memory formation in APP/PS1 mice

Bartosz Jura,Pierre Meyrand,Nathalie Macrez,Tiaza Bem

doi:10.1038/s41598-019-56582-w

Abstract

General theory of declarative memory formation posits a cortical-hippocampal dialog during which hippocampal ripple oscillations support information transfer and long-term consolidation of hippocampus dependent memories. Brain dementia, as Alzheimer disease (AD), is accompanied by memory loss and inability to form new memories. A large body of work has shown variety of mechanisms acting at cellular and molecular levels which can putatively play an important role in the impairment of memory formation. However, far less is known about changes occurring at the network-level activity patterns that support memory processing. Using freely moving APP/PS1 mice, a model of AD, we undertook a study to unravel the alterations of the activity of hippocampal and cortical circuits during generation of ripples in the transgenic and wild-type mice undergoing encoding and consolidation of spatial information. We report that APP/PS1 animals are able to consolidate spatial memory despite a major deficit of hippocampal ripples occurrence rate and learning dependent dynamics. We propose that these impairments may be compensated by an increase of the occurrence of cortical ripples and reorganization of cortical-hippocampal interaction.

Highlights

General theory of declarative memory formation posits a cortical-hippocampal dialog during which hippocampal ripple oscillations support information transfer and long-term consolidation of hippocampus dependent memories
To characterize the effect of amyloid precursor protein (APP)/PS1 modification on spatial memory processing, APP/PS1 and wild-type littermate control (WT) mice were trained during 6 days to navigate in an 8-arm radial maze to learn the spatial position of three arms containing food rewards (Fig. 1a2)
Our results show that APP/PS1 are able to learn spatial reference memory task despite major impairment of hippocampal ripple features compared to their littermate control, suggesting an adaptive reconfiguration of neural circuits involved in spatial memory formation

Summary

Introduction

General theory of declarative memory formation posits a cortical-hippocampal dialog during which hippocampal ripple oscillations support information transfer and long-term consolidation of hippocampus dependent memories. In the intact brain of rodents a large body of work has been focused on memory formation driven by hippocampal ripples, the high frequency network events generated during slow wave sleep (SWS) and consummatory behaviors[7,8,9,10]. Their major function is the transfer of information between hippocampus and cortex while other subcortical structures are silent[11]. In this study we report that APP/PS1 animals are still able to consolidate spatial memory despite a major deficit of hippocampal ripples which may be www.nature.com/scientificreports compensated by an increase of the occurrence of cortical ripples and ripple-to-ripple cortical-hippocampal interaction or by an increased number of trial-and-error events

Methods

Results

Conclusion