Orchestrated ensemble activities constitute a hippocampal memory engram

Hirotaka Asai,Kaoru Inokuchi,Mina Matsuo,Khaled Ghandour,Yoshito Saitoh,Masaaki Sato,Shingo Soya,Chi Chung Alan Fung,Yasunori Hayashi,Takeshi Sakurai,Masamichi Ohkura,Junichi Nakai,Tomoki Fukai,Makoto Osanai,Takashi Takekawa,Noriaki Ohkawa,Hirofumi Nishizono,Takashi Kitamura,Reiko Okubo-Suzuki

doi:10.1038/s41467-019-10683-2

Abstract

The brain stores and recalls memories through a set of neurons, termed engram cells. However, it is unclear how these cells are organized to constitute a corresponding memory trace. We established a unique imaging system that combines Ca2+ imaging and engram identification to extract the characteristics of engram activity by visualizing and discriminating between engram and non-engram cells. Here, we show that engram cells detected in the hippocampus display higher repetitive activity than non-engram cells during novel context learning. The total activity pattern of the engram cells during learning is stable across post-learning memory processing. Within a single engram population, we detected several sub-ensembles composed of neurons collectively activated during learning. Some sub-ensembles preferentially reappear during post-learning sleep, and these replayed sub-ensembles are more likely to be reactivated during retrieval. These results indicate that sub-ensembles represent distinct pieces of information, which are then orchestrated to constitute an entire memory.

Highlights

The brain stores and recalls memories through a set of neurons, termed engram cells
To understand how contextual memories are represented in engram cells, we first confirmed that cells labelled with c-fos during contextual exposure do store the contextual memory
We injected lentivirus (LV)-expressing channelrhodopsin-2 (ChR2) or enhanced yellow fluorescent protein (EYFP) under the control of tetracycline-responsive element (TRE) in c-fos-tTA transgenic mice[5]. This system ensures that only the neurons in the ensemble specific to a certain event will be labelled with ChR2 or EYFP

Summary

Introduction

The brain stores and recalls memories through a set of neurons, termed engram cells. it is unclear how these cells are organized to constitute a corresponding memory trace. Reduced theta power during rapid eye movement (REM) sleep weakens previously acquired hippocampus-dependent memories[15] These findings imply that, during the post-learning period, specific activity in a certain group of cells represents and governs the maintenance of a given memory trace. The orchestration of neural ensembles is likely the counterpart for complex information Recent techniques such as Ca2+ imaging provide an opportunity to observe and track the activity of a large number of neurons simultaneously over long time periods in freely behaving mice[17,18], enabling the functional importance of these assemblies during the post-learning period to be decoded. In contrast to non-engram cells, these ensembles maintain their activity during learning and during post-learning sleep and retrieval sessions

Methods

Results

Conclusion