Pacing Hippocampal Sharp-Wave Ripples With Weak Electric Stimulation.

Huiyi Jiang,Jianyoung Wu,Adam Caccavano,Shicheng Liu,Katherine Conant,Xinling Geng,Stefano Vicini

doi:10.3389/fnins.2018.00164

Abstract

Sharp-wave ripples (SWRs) are spontaneous neuronal population events that occur in the hippocampus during sleep and quiet restfulness, and are thought to play a critical role in the consolidation of episodic memory. SWRs occur at a rate of 30–200 events per minute. Their overall abundance may, however, be reduced with aging and neurodegenerative disease. Here we report that the abundance of SWR within murine hippocampal slices can be increased by paced administration of a weak electrical stimulus, especially when the spontaneously occurring rate is low or compromised. Resultant SWRs have large variations in amplitude and ripple patterns, which are morphologically indistinguishable from those of spontaneous SWRs, despite identical stimulus parameters which presumably activate the same CA3 neurons surrounding the electrode. The stimulus intensity for reliably pacing SWRs is weaker than that required for inducing detectable evoked field potentials in CA1. Moreover, repetitive ~1 Hz stimuli with low intensity can reliably evoke thousands of SWRs without detectable LTD or “habituation.” Our results suggest that weak stimuli may facilitate the spontaneous emergence of SWRs without significantly altering their characteristics. Pacing SWRs with weak electric stimuli could potentially be useful for restoring their abundance in the damaged hippocampus.

Highlights

Sharp-wave ripples (SWRs) are spontaneous neuronal population events that occur in the hippocampus during sleep and quiet restfulness (John and Lynn, 1979; O’keefe and Nadel, 1979; Buzsáki et al, 1983; Axmacher et al, 2008; Buzsáki, 2015)
In this report we explore to increase the abundance of SWRs by “pacing”, i.e., to initiate SWR events by low intensity electrical shocks given at a rate similar to the spontaneously occurring rate
We address three questions using our in vitro model: (1) Can low intensity stimuli reliably increase the abundance of SWRs? (2) Can weak stimuli reliably evoke SWRs, without long term depression (LTD) or other habituation effects that may follow from stimulation that is of low frequency or intensity? (3) Can highly diverse SWRs be initiated given that the external stimulus is repeatedly delivered in proximity to the same neurons? Our results show promising answers

Summary

Introduction

Sharp-wave ripples (SWRs) are spontaneous neuronal population events that occur in the hippocampus during sleep and quiet restfulness (John and Lynn, 1979; O’keefe and Nadel, 1979; Buzsáki et al, 1983; Axmacher et al, 2008; Buzsáki, 2015). An experience, such as field exploration, is registered in the hippocampus as sequential activations of neuronal assemblies (aka “place cell assemblies”). This reactivation is likely to represent a key component of the “two-step” hypothesis of memory consolidation (Buzsáki, 1989)

Methods

Results

Conclusion