Stability and change in the memory system during rest ISTA Thesis Bollmann, Lars Memory Hippocampus Consolidation ddc:573 Acquiring, retaining, and retrieving information over a wide range of timescales are crucial functions of the brain. The successful processing of memories affects many aspects of our lives and enables us and many other organisms to operate in a complex environment and to interact with it. In this context, the hippocampus and functionally connected brain areas, such as the prefrontal cortex, are central and have been subject to intensive research in the past decades. Storage of memories is believed to rely on distributed neural activity within these neural circuits. Additionally, neural memory traces of recent experience are reinstated during periods of rest or sleep. These reactivations are thought to play an outstanding role in the consolidation of memories and potentially facilitate the transfer of information from the hippocampus to cortical areas for long-term storage and integration into existing knowledge. However, there is growing evidence that memory-related neural representations in the hippocampus are not as stable as initially thought and that they change even in the absence of learning. It has been suggested that these changes reflect the accumulation of experience, but the influence of interspersed consolidation periods has not been considered. Previous studies have analyzed consolidation periods by detecting activity that strongly resembled neural activity during the acquisition of memory. Besides being often limited to only non-rapid eye movement (NREM) sleep, the used approaches were not capable of tracking changes in neural representations over extended temporal periods. More fluid representations do not only challenge our understanding of how information is stored, but they also affect the transfer of information between brain areas during the consolidation process. For this thesis, I investigated the evolution of memory-related activity during sleep periods expected to be involved in consolidation in the hippocampus and between the hippocampus and prefrontal cortex. I found that reactivated activity in the hippocampus gradually transformed during prolonged periods of sleep and inactivity. In the beginning, neural activity strongly resembled acquisition activity, whereas, with the progression of time, it became more similar to the subsequent recall activity. NREM periods drove this process, while rapid-eye movement (REM) periods showed a resetting effect. This reactivation drift was due to firing rate changes of a subset of cells and mirrored the representational changes from the acquisition to the recall. A stable subset of cells withstood the drift and maintained their activity. Therefore, my results indicate that memory-related representations undergo spontaneous modifications during consolidation periods and that these changes are predictive of representational drift. Furthermore, I found that the amount of change in the neural activity during subsequent sleep periods was biased by prior behavioral performance. Observed changes in the hippocampus and the prefrontal cortex were synchronized and increased after poor performance, highlighting a potential role in the exchange of information. Low-variance vii periods with distinct, more stable activity from a subset of cells significantly contributed to the heightened synchrony between both areas. Hence, interleaved phases of more stable neural activity could facilitate the information transfer between brain areas. In conclusion, my investigations underline the fluidity of memory-related representations and assign a prominent role to sleep reactivation periods in their evolution. In addition, I identified a potential mechanism of stable activity phases that might facilitate the synchronization across hippocampal-prefrontal activity despite ongoing changes. Reconciling and integrating findings from both spontaneous and behaviorally-related representational changes in functionally related brain areas will help to broaden our understanding of how knowledge is stored, maintained, updated, and transferred between brain areas. Institute of Science and Technology Austria 2024 info:eu-repo/semantics/doctoralThesis doc-type:doctoralThesis text http://purl.org/coar/resource_type/c_db06 https://research-explorer.ista.ac.at/record/17346 https://research-explorer.ista.ac.at/download/17346/17359 Bollmann L. Stability and change in the memory system during rest. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17346">10.15479/at:ista:17346</a> eng info:eu-repo/semantics/altIdentifier/doi/10.15479/at:ista:17346 info:eu-repo/semantics/altIdentifier/issn/2663-337X info:eu-repo/semantics/openAccess