Learning to remember: the development of the neural mechanisms supporting memory processing.

The ability to form and store memories allows organisms to learn from the past and imagine the future: it is a crucial mechanism underlying flexible and adaptive behaviour. The aim of this proposal is to identify the circuit mechanisms underlying our ability to learn and remember, by tracking the ontogenesis of memory processing. Importantly, we are not born with a fully functioning memory system: generally, adults cannot recollect any events from before their third birthday (‘infantile amnesia’). There are several accounts as to the source of this mnemonic deficit, each placing emphasis on impairments of specific processes (encoding, consolidation, retrieval). However, a general weakness in the study of memory ontogeny is the lack of neural data describing the activity of memory-related circuits during development. To directly address this knowledge gap, we propose to study the ontogeny of brain-wide hippocampus-centred memory networks in the rat. We will study to which extent memory expression relies on spatial signalling, delineate the role of sleep in memory consolidation, determine how hippocampal planning-related neuronal activity influences memory processing, understand whether the rapid forgetting observed in development is due to interference, and explore interactions between the hippocampus, pre-frontal and striatal circuits in orchestrating memory emergence. We are best placed to deliver this ambitious experimental plan due to our extensive experience of in vivo recording in developing rats which we will couple with the application of recently emerged technologies (2-photon imaging, high density electrophysiology, chemogenetic manipulation of neural activity). As our studies of the development of hippocampal spatial representations have delivered powerful insights into their adult function, we expect the work outlined here to critically advance our understanding not only of development, but also of healthy memory processing in adulthood.