In the first phase of the project, we have been focused on establishing methods to perform recordings of large populations of neurons in the developing mouse hippocampus, on developing behavioural paradigms that can be learned with similar efficacy by both infant and adult mice, on establishing robust and reliable setups for the artificial stimulation or silencing of targeted populations of neurons, and on developing and streamlining analysis pipelines for the quantitative interrogation of data acquired with the previous techniques. These efforts have been essential for performing the experiments related to the second phase of the project. In the first line of research, we have recorded the activity of a large fraction of the neural network comprising the CA3 area of the hippocampus longitudinally, through stages of development that are associated with distinct learning potential – i.e. with a mouse's ability to learn more and more complex cognitive tasks. These experiments have allowed us to compare changes in the statistics of network activity and connectivity with a developing animal's performance in spatial learning tasks, and dissect the mechanisms by which developmentally-driven network remodelling underpins the increase in cognitive flexibility of a developing animal. In the second line of research, we have mapped the recruitment of neurons characterised by specific developmental trajectories (i.e. neurogenesis) into memory traces at different stages of an animal's life, to reveal a time-dependent change in the circuitry involved in encoding and storage of memories during the development and adulthood. In the third line of research, we have targeted neurons involved in memory formation during infancy for their reactivation later in life and investigated how the activity of neurons associated with memories that are inaccessible for recall in the adult brain would influence learning processes and the behaviour of the animal.
Our experiments indicate that in the adult hippocampus, multiple memory traces form within distinct neuronal subpopulations defined by neurogenesis and functional specialization. The separate recruitment of these subpopulations drives the evolving nature of memories, ultimately determining whether a memory remains open to modification over time. This divergence gradually emerges during development in conjunction with cognitive milestones, such as the capacity to create enduring memories. Finally, we observed that infant memory traces remain intact in the adult brain despite their apparent loss and that their activation is essential for reinstating a forgotten early-life memory.
This research has been repeatedly disseminated at national and international conferences through the years by both the principal investigator and the PhD Students and Postdocs who took part in the work. While one line of research has led to a publication led by PhD student Vilde Aamodt Kveim in 2024 (Kveim et al., Science 2024), the others are currently in preparation for submission to scientific journals.
