Grant: Project Grant

Forgetting is commonly perceived as a failure of normal memory. Yet, in the last decade it has become increasingly clear that much of everyday forgetting results from dedicated forgetting processes that are built into the brain, which seem necessary for the brain to function normally. We have shown that one of these forgetting processes systematically reduces the strength of connections between neurons over time. This "active decay" process gradually disassembles the neuronal structures supporting memory, leading to memory loss. We now wish to learn more about active decay, which seems responsible for a significant amount of everyday forgetting: (1) It is known that programmed, controlled cell death involves the disassembly of the connections between neurons. We therefore will to test whether the same molecular events that trigger the disassembly of connections during cell death could also be involved in normal, everyday forgetting without causing cell death. (2) We aim to better understand how exactly decay reduces the strength of connections between neurons, and how this process is regulated. (3) Finally, we will explore whether dysfunction of this forgetting process contributes to certain cognitive problems. In autism spectrum disorder, for example, inflexibility in adjusting behavior might reflect a problem in forgetting inadequate responses, which can persist and disrupt normal functioning. We will try to restore normal forgetting in rat strains that carry genetic modifications found in neurodevelopmental intellectual disorders. Better understanding forgetting will provide us with vital knowledge about the normal functioning of the healthy brain. This will also help us understand how dysfunctional forgetting contributes to disorders of the brain in which individuals forget too little or too much, which is the case in some neurodevelopmental disorders, such as autism spectrum disorders, and neurodegenerative disorders, such as Alzheimer's disease.