Studies on synaptic engram in hippocampus and amygdala using Dual-eGRASP

Abstract

Our daily experiences are stored in the brain as form of memories and define one person's individuality. It has long been human beings interests, where and how the memory is encoded in our brain. In this acquisition and storage process of memories, structural and physiological changes occur, which is considered as the physical substrates of the memory or the engram. During the memory formation, synapses between neurons undergo plasticity. Neurobiologists have tried to observe these changes in the synapses between engram cells. However, substrate at synapse-level within engram cells remains elusive, because of technical limitations. To distinguish the connections between engram cell and other neurons, I developed and applied dual-eGRASP technique. Using Dual-eGRASP, I could capture the Synaptic engrams in the hippocampus and amygdala, which are the connections between pre- and post-synaptic engram cells among intermingled neuronal ensembles. Tracking the synaptic engram in hippocampus CA3 to CA1 Schaffer-collateral pathway, I found the strength of memory is correlated with density and spine size of synaptic engrams, not depend on number of engram cells. Moreover, in the lateral amygdala (LA), I found that extinction of fear memory reversed the synaptic enhancement induced by fear conditioning. In addition, re-conditioning with same tone and shock recovered the spine size of synaptic engram decreased by fear extinction. These results indicate that the connections between engram cells, synaptic engram, represents the state of memory. These synaptic-level engram approaches will provide information on the question, how the memory is encoded in our brain.