Gone or Misplaced?: Investigation of Memory Engrams Across Development

Abstract

All humans experience amnesia. While about 30% of adults who live to be over 65 will suffer from dementia, 100% of the human population experiences infantile amnesia, which is the loss of memories formed in early childhood (before 2 4 years). Although behavioural neuroscientists have already demonstrated that rodents display infantile amnesia, little is known about the basic neurobiology of infantile amnesia and further its effect on memory engrams. This thesis probes the question of how memories are stored in the brain throughout development by integrating recently developed engram labelling technology with rodent models of infantile amnesia. This thesis aims to characterize infantile amnesia in the mouse using multiple behavioural paradigms. It develops a genetic strategy for labelling infant engram cells in a persistent way that can be maintained across the lifespan. It then uses this strategy as a platform to optogenetically interrogate the functionality of infant engram cells in adulthood. It investigates the degree of information content that is retained after infantile amnesia for various kinds of memory. The mechanisms underlying infantile amnesia are investigated and potential methodologies for the permanent reinstatement of infant engrams are probed. Lastly, approaches for preventing infantile amnesia are explored by inducing immunological brain states that may allow infant memories to survive IA.