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Mechanisms underlying dentate gyrus interneuron plasticity and their role in controlling population activity /in vivo/

Subject Area Molecular Biology and Physiology of Neurons and Glial Cells
Term from 2014 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 245861656
 
Despite intensive study in the past on the problem of how information is processed in the brain to enable individual organisms to adapt to their continuously changing environment, little progress has been made on how memory traces emerge in neuronal networks during learning. Current theories suggest that experience-dependent modifications of synaptic weights enable a selected group of neurons to form a new cell association during learning which represents the new memory trace (Buzsáki, 2010). However, how cell associations emerge in space and time and how GABAergic cells may contribute to this process is still largely unknown. We hypothesise that long-lasting plastic changes in the efficacy of glutamatergic transmission onto GABAergic inhibitory cells are essential for this process. We aim to address this fundamental hypothesis at granule cell (GC) output synapses targeting parvalbumin (PV)-expressing perisomatic-inhibitiory interneurons (PVIs) and somatostatin (SOM)-positive dendritic-inhibitory interneurons (SOMIs) in the rodent dentate gyrus (DG). In the last funding period, we gained detailed knowledge on the molecular mechanisms underlying long-lasting plastic changes at GC-PVI terminals (Hainmüller et al., 2014). Here, we aim (1) to determine the main molecular signalling cascades underlying plastic changes at glutamatergic inputs onto DG-SOMIs by using whole-cell recordings in hippocampal slice preparations (Yuan, Meyer et al., 2017). (2) Together with our knowledge on DG’s cellular elements and their inter-connectivity, we will examine the spatial and temporal activity patterns of cell populations in the DG during spatial learning in a virtual-reality using 2-Photon (2P) imaging. (3) Based on our knowledge gained during the 1st funding period on the molecular mechanisms underlying PVI plasticity, we will determine their role in cell assembly formation and behavior by applying optogenetic and molecular interference tools established by our partners. Thus, the here proposed project in the 2nd funding period will provide detailed information on the role of interneuron (IN) plasticity in cell assembly formation and thereby to information processing in the DG.
DFG Programme Research Units
 
 

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