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The impact of interneuron plasticity on engram and memory formation in the hippocampus

Subject Area Molecular Biology and Physiology of Neurons and Glial Cells
Term from 2014 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 245861656
 
Principal cells are viewed as the processing units of brain computations. They encode information in their activity patterns and communicate this information to other local or distant principal cells. In addition, principal cells show experience-dependent functional and structural changes in synaptic transmission and connectivity. Such plasticity allows the organism to adapt to new situations and to form memories. Principal cell activity, however, is tightly regulated in time and space by various types of inhibitory GABAergic interneurons. A number of recent studies, including some from our research unit (RU), have shown that contrary to a long standing belief synapses onto interneurons (INs) are also subject to strong plastic changes. This is highly relevant as changes in the connectivity or recruitment of GABAergic inhibitory cells may have profound effects on the temporal and spatial activity patterns of principal cells. During the first funding period of the research unit we were able to demonstrate for the first time that perisomatic-targeting parvalbumin (PV)-expressing INs (PVIs) in the dentate gyrus carry large numbers of dendritic spines, which determine plastic changes in protein expression and which undergo input selective structural plasticity in response to behavioural challenge. We also showed that dendrite-targeting SOMIs in the dentate gyrus are crucial for spatial memory precision and the coordination of engram cells. Importantly, during this period we have developed a number of molecular tools for cell type- and circuit-specific interference with IN plasticity, which we will now apply to probe the functional impact of IN plasticity at the level of neuronal networks and behaving mice. Beyond this we will use immediate early gene imaging to investigate whether hippocampal INs themselves become part of a memory engram.
DFG Programme Research Units
 
 

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