Memory exerts a powerful influence over behavior. The ability of past experiences to guide future actions suggests there is an internal representation of those experiences stored in the brain. The term “engram” was introduced by Richard Semon to describe the neurobiological basis of memory storage. More concretely, engrams are defined as “the enduring offline physical and/or chemical changes that were elicited by learning and underlie the newly formed memory associations” (Josselyn and Tonegawa, 2020). They are thought to be activated during initial learning experiences and reactivated upon subsequent exposure to stimuli present during encoding to enable memory retrieval.
Fear conditioning is a powerful paradigm for studying in rodent models the behavioral expression of memory, including the existence and influence of engrams. In fear conditioning, a neutral cue becomes associated with an aversive stimulus over repeated pairings, such that the previously neutral cue starts to elicit the expression of stereotyped freezing behavior. This expression of fear via freezing provides a behavioral read-out, or index, of memory retrieval that is easily measurable.
Recent technical developments have enabled researchers to identify engrams and elucidate their mechanistic role in producing freezing responses. The existence of engram cells was shown by using fluorescent proteins to separately tag neurons active during fear conditioning, and those reactivated during freezing, i.e., fear memory retrieval (Reijmers et al., 2007). Engram cells were defined as neurons expressing both fluorescent markers. Using similar techniques, researchers can express light-gated ion channels specifically in engram populations. This enables them to test the causal role of engram cell activity on memory retrieval, by manipulating the activity of these cells while monitoring behavior. After fear conditioning, inactivating engram cells when the animal is in the fear-eliciting context disrupts freezing (Han et al., 2009), whereas optically stimulating these engram cells in …
Correspondence should be addressed to Chloé Guillaume at cg829{at}cam.ac.uk.
