Engram Cell Excitability State Determines the Efficacy of Memory Retrieval

Michele Pignatelli; Tomás J Ryan; Dheeraj S Roy; Chanel Lovett; Lillian M Smith; Shruti Muralidhar; Susumu Tonegawa

doi:10.1016/j.neuron.2018.11.029

Engram Cell Excitability State Determines the Efficacy of Memory Retrieval

Neuron. 2019 Jan 16;101(2):274-284.e5. doi: 10.1016/j.neuron.2018.11.029. Epub 2018 Dec 11.

Authors

Michele Pignatelli¹, Tomás J Ryan², Dheeraj S Roy³, Chanel Lovett², Lillian M Smith³, Shruti Muralidhar³, Susumu Tonegawa⁴

Affiliations

¹ RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: pignatel@mit.edu.
² RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴ RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: tonegawa@mit.edu.

PMID: 30551997
DOI: 10.1016/j.neuron.2018.11.029

Abstract

Animals need to optimize the efficacy of memory retrieval to adapt to environmental circumstances for survival. The recent development of memory engram labeling technology allows a precise investigation of the processes associated with the recall of a specific memory. Here, we show that engram cell excitability is transiently increased following memory reactivation. This short-term increase of engram excitability enhances the subsequent retrieval of specific memory content in response to cues and is manifest in the animal's ability to recognize contexts more precisely and more effectively. These results reveal a hitherto unknown transient enhancement of context recognition based on the plasticity of engram cell excitability. They also suggest that recall of a contextual memory is influenced by previous but recent activation of the same engram. The state of excitability of engram cells mediates differential behavioral outcomes upon memory retrieval and may be crucial for survival by promoting adaptive behavior.

Keywords: engram; excitability; hippocampus; inward rectifier potassium channels; memory; memory access; memory retrieval; pattern completion; pattern separation; recognition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anisomycin / pharmacology
Bacterial Proteins / genetics
Channelrhodopsins / genetics
Channelrhodopsins / metabolism
Conditioning, Psychological / physiology
Dentate Gyrus / cytology*
Doxycycline / pharmacology
Freezing Reaction, Cataleptic / drug effects
Freezing Reaction, Cataleptic / physiology
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Imidazoles / pharmacology
Luminescent Proteins / genetics
Membrane Potentials / drug effects
Membrane Potentials / physiology*
Mental Recall / drug effects
Mental Recall / physiology*
Mice
Mice, Transgenic
Microscopy, Confocal
Neurons / drug effects
Neurons / physiology*
Patch-Clamp Techniques
Phenanthrolines / pharmacology
Potassium Channels, Inwardly Rectifying / genetics
Potassium Channels, Inwardly Rectifying / metabolism
Protein Synthesis Inhibitors / pharmacology
Transduction, Genetic

Substances

2-(2-methyl-1H-indol-3-yl)-1H-imidazol(4,5-f)(1,10)phenanthroline
Bacterial Proteins
Channelrhodopsins
Imidazoles
Kir2.1 channel
Luminescent Proteins
Phenanthrolines
Potassium Channels, Inwardly Rectifying
Protein Synthesis Inhibitors
yellow fluorescent protein, Bacteria
Anisomycin
Doxycycline