Periodic Reporting for period 1 - FUS-REPLAY (Tracking and decoding individual memories across the brain from creation to long-term storing)
Reporting period: 2022-04-14 to 2024-04-13
How can we vividly remember so many episodes of our life that, by definition, only happened once? During wakefulness, the hippocampus – a brain structure critical for episodic memory – encodes ‘memory traces’ of our experience. During sleep, it “replays” the very same sequences of neurons that were originally activated during the awake episode. Such reactivations are essential for memory consolidation. Over the years, a growing body of studies have unveiled “on-site” reactivations within the hippocampus, sometimes with a neocortical or subcortical “partner” structure, but the overall activity in the brain during these events remains largely unknown.
This is a major knowledge gap because numerous cortical and subcortical structures strongly influence memory. Observing the key structures and the neural correlates of memory consolidation during sleep can have a significant impact on pathologies where such memory traces are over consolidated in conditions like posttraumatic stress disorders syndrome as for numerous neurogenerative disorders such as Alzheimer’s or Parkinson’s diseases are associated with disrupted memory processes and altered sleep architecture. The scope of this project is thus very broad and its impact far-reaching.
In this project, we aim to use a unique combination of groundbreaking recording and analysis techniques to reveal the whole-brain correlates of hippocampal replay and their dynamics throughout the life of a single memory from its creation to its long-term storage. In particular, the technique of functional ultrasound will enable us to track brain activity with unprecedented resolution during a well-defined behavioral task.
This is a major knowledge gap because numerous cortical and subcortical structures strongly influence memory. Observing the key structures and the neural correlates of memory consolidation during sleep can have a significant impact on pathologies where such memory traces are over consolidated in conditions like posttraumatic stress disorders syndrome as for numerous neurogenerative disorders such as Alzheimer’s or Parkinson’s diseases are associated with disrupted memory processes and altered sleep architecture. The scope of this project is thus very broad and its impact far-reaching.
In this project, we aim to use a unique combination of groundbreaking recording and analysis techniques to reveal the whole-brain correlates of hippocampal replay and their dynamics throughout the life of a single memory from its creation to its long-term storage. In particular, the technique of functional ultrasound will enable us to track brain activity with unprecedented resolution during a well-defined behavioral task.
From the beginning of the project, we have acquired a large dataset of vascular activity over the whole brain (recorded with functional ultrasound imaging) with simultaneous electrophysiological activity in the hippocampus and neighboring structures. These data are the first of their kind and will considerably enhance our understanding of the phenomenon of replay during sleep. In a second set of experiment, we have started decoding the content of this hippocampal replay to disentangle individual memories during sleep base on their resemblance with specific activities recorded during wake.
The dataset produced in the fUS-REPLAY project will be of great interest for the neuroscience community. Not only did we collect brain activity in vast portions of the rodent brain during sleep and wake, but we also characterized the spatiotemporal dynamics of replay with a level of precision that was unachieved before. In particular we are in a unique position to track the transfer of memories from hippocampal to neocortical sites, where they are supposedly more resistant to forgetting. If successful, our project will carry the biological substrates of memory and will raise hope to counter the aberrant mechanisms at play in neurodegenerative models as well as during maladaptive learning such as traumatic events, with a global positive impact for society at large.