Mapping the prefrontal cortex : structure, activity, function

<p dir="ltr">The mouse prefrontal cortex (PFC) is an umbrella term for rostrally located neocortical brain regions. The PFC serves a fundamental role in computing and integrating signals underlying the generation of purposeful, goal-directed actions. Despite increasing knowledge about the molecular, morphological, and physiological diversity of PFC networks, our current knowledge about the exact mechanisms of prefrontal action remains limited.</p><p dir="ltr">In the present thesis, we aimed at filling this knowledge gap by creating detailed maps of the PFC based on different structural and functional criteria agnostic to preconceived borders of PFC subregions. As mapping the PFC requires adequate methods, we developed two research tools that enable researchers to map the brain. The DMC-Behavior Platform allows for rigid and standardized training of head-fixed mice on auditory detection and decision-making tasks, while DMC- BrainMap is a software for mapping of anatomical features to reference spaces in different model organisms.</p><p dir="ltr">We subsequently created maps of the PFC based on structural and functional criteria including the anatomical organization of prefrontal top-down projections and spontaneous as well as task-related prefrontal activity patterns. We found that the mappings of the respective features do not adhere to preconceived delineations of PFC subregions, but are organized in spatially cohesive modules transcending PFC subregion borders, or in networks distributed across the entire PFC.</p><p dir="ltr">These findings challenge the notion that brain regions constitute the fundamental organization unit of the PFC to which functional labels can be assigned, and warrant a careful re-examination of existing findings concerning the structural and functional organization of the PFC. Conversely, a data-driven research approach, as exemplified in this thesis, harbors the potential to elucidate previously uncharted organizational principles of the PFC, with the prospect of understanding PFC function in health and disease.</p><h3>List of scientific papers</h3><p dir="ltr">I. DMC-Behavior Platform: An Open-Source Framework for Auditory-Guided Perceptual Decision-Making in Head-Fixed Mice. <b>Jung, F.</b>, Cao, X., Heymans, L., Carlén, M. eNeuro, 2025 Apr 10;12(4):ENEURO.0457-24.2025. <a href="https://doi.org/10.1523/ENEURO.0457-24.2025" rel="noreferrer" target="_blank">https://doi.org/10.1523/ENEURO.0457-24.2025</a><br><br></p><p dir="ltr">II. DMC-BrainMap - an open-source, end-to-end tool for multi- feature brain mapping across species. <b>Jung, F.</b>, Cao, X., Heymans, L., Carlén, M. bioRxiv (preprint), 2025. <a href="https://doi.org/10.1101/2025.02.19.639009" rel="noreferrer" target="_blank">https://doi.org/10.1101/2025.02.19.639009</a></p><p dir="ltr">III. Mouse prefrontal cortex displays region- and cell-type-specific projections to sensory cortices. <b>Jung, F.</b>, Heymans, L., Cao, X., Carlén, M. [Manuscript]</p><p dir="ltr">IV. A Prefrontal Cortex Map based on Single Neuron Activity. Le Merre, P., Heining, K., Slashcheva, M., <b>Jung, F.</b>, Moysiadou, E., Guyon, N., Yahya, R., Park, H., Wernstal, F., Carlén, M. bioRxiv (preprint), 2024. <a href="https://doi.org/10.1101/2024.11.06.622308" rel="noreferrer" target="_blank">https://doi.org/10.1101/2024.11.06.622308</a></p><p dir="ltr">V. Esr1+ hypothalamic-habenula neurons shape aversive states. Calvigioni, D., Fuzik, J.,Le Merre, P., Slashcheva, M., <b>Jung, F.</b>, Ortiz, C., Lentini, A., Csillag, V., Graziano, M., Nikolakopoulou, I., Weglage, M., Lazaridis, I., Kim, H., Lenzi, I., Park, H., Reinius, B., Carlén, M., Meletis, K. Nature Neuroscience, 2023 Jul;26(7):1245-1255. <a href="https://doi.org/10.1038/s41593-023-01367-8" rel="noreferrer" target="_blank">https://doi.org/10.1038/s41593-023-01367-8</a><br></p>