School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany; Max Planck Research Group NeuroCode, Max Planck Institute for Human Development, Berlin, Germany
Livia Autore
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Melbourne, Australia; Child & Brain Development Program, Canadian Institute for Advanced Research (CIFAR), Toronto, Canada
Memories are stored as ensembles of engram neurons and their successful recall involves the reactivation of these cellular networks. However, significant gaps remain in connecting these cell ensembles with the process of forgetting. Here, we utilized a mouse model of object memory and investigated the conditions in which a memory could be preserved, retrieved, or forgotten. Direct modulation of engram activity via optogenetic stimulation or inhibition either facilitated or prevented the recall of an object memory. In addition, through behavioral and pharmacological interventions, we successfully prevented or accelerated forgetting of an object memory. Finally, we showed that these results can be explained by a computational model in which engrams that are subjectively less relevant for adaptive behavior are more likely to be forgotten. Together, these findings suggest that forgetting may be an adaptive form of engram plasticity which allows engrams to switch from an accessible state to an inaccessible state.
