Normal and Abnormal Sharp Wave Ripples in the Hippocampal-Entorhinal Cortex System: Implications for Memory Consolidation, Alzheimer's Disease, and Temporal Lobe Epilepsy

Zhi-Hang Zhen,Jun-Li Zhen,Jian Fu,He-Ming Li,Mo-Ran Guo,Guo-Jun Tan,Ou-Yang Guo

doi:10.3389/fnagi.2021.683483

Abstract

The appearance of hippocampal sharp wave ripples (SWRs) is an electrophysiological biomarker for episodic memory encoding and behavioral planning. Disturbed SWRs are considered a sign of neural network dysfunction that may provide insights into the structural connectivity changes associated with cognitive impairment in early-stage Alzheimer's disease (AD) and temporal lobe epilepsy (TLE). SWRs originating from hippocampus have been extensively studied during spatial navigation in rodents, and more recent studies have investigated SWRs in the hippocampal-entorhinal cortex (HPC-EC) system during a variety of other memory-guided behaviors. Understanding how SWR disruption impairs memory function, especially episodic memory, could aid in the development of more efficacious therapeutics for AD and TLE. In this review, we first provide an overview of the reciprocal association between AD and TLE, and then focus on the functions of HPC-EC system SWRs in episodic memory consolidation. It is posited that these waveforms reflect rapid network interactions among excitatory projection neurons and local interneurons and that these waves may contribute to synaptic plasticity underlying memory consolidation. Further, SWRs appear altered or ectopic in AD and TLE. These waveforms may thus provide clues to understanding disease pathogenesis and may even serve as biomarkers for early-stage disease progression and treatment response.

Highlights

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of deposits containing β-amyloid protein and neurofibrillary tangles in brain gray matter concomitant with progressive cognitive decline, which usually starts with deficits in episodic memory
Coherence Analysis of hippocampal-entorhinal cortex (HPC-EC) System lobe epilepsy (TLE), as epileptic seizures are often present in AD patients and amyloid plaques were first described in epileptic patients (Nicastro et al, 2016; Zarea et al, 2016), suggesting shared risk factors and pathomechanisms
It is believed that ensemble formation is mediated in part by use-dependent synaptic plasticity, such as NMDA receptor (NMDAR)-dependent longterm potentiation (LTP), initiated by oscillatory brain activity and regulated by a variety of neuromodulators such as brain-derived neurotrophic factor (BDNF), dopamine, and acetylcholine (ACh)

Summary

Introduction

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of deposits containing β-amyloid protein (amyloid plaques) and neurofibrillary tangles in brain gray matter concomitant with progressive cognitive decline, which usually starts with deficits in episodic memory. Hippocampal theta oscillations alone are capable of linking and segregating the firing of neuronal assemblies (for review, see Hanslmayr and Staudigl, 2014), we present evidence that SWRs are essential for synaptoplastic processes, network reorganization, and signaling among brain structures involved in memory consolidation.

Results

Conclusion