Project Details
Projekt
The role of microglial cytoskeleton proteins ADF/Cfl1 in learning and memory
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Cognitive, Systems and Behavioural Neurobiology
Cognitive, Systems and Behavioural Neurobiology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 500305540
Microglia are resident macrophages of the central nervous system (CNS), where they act as first immune response to pathogens. Moreover, microglia are highly motile cells that are associated with the regulation of CNS homeostasis and neuronal function. However, how microglia interact with neurons and vice versa in different brain regions is poorly understood. The cytoskeleton proteins “actin depolarizing factor” (ADF) and Cofilin-1 (Cfl1) have been shown to be crucial in neuronal development, function and cell cycle control. In microglia the role of ADF/Cfl1 remains unknown, although microglial scanning of the brain parenchyma with fine processes most likely requires a fast assembly and disassembly of actin filaments. In the hippocampus, a brain region relevant for learning and memory, we recently identified a relationship between motility of fine microglial processes and neuronal activity, as well as synapse stability. It is tempting to speculate that cytoskeleton-dependent fine process motility of microglia relates to neuronal function and even cognition. Therefore, we hypothesize that microglia function strongly depends on the cytoskeleton proteins ADF/cofilin1 and that their functionality is crucial for neuronal networks contributing to learning and memory.We will address this hypothesis by employing state of the art in vivo two-photon microscopy of neurons and microglia in the hippocampus of the behaving animal performing a spatial memory test. In order to decipher the role of ADF/Cfl1 in microglia and its importance for neuronal networks, functional imaging of spatially-tuned place cells and microglia motility will be monitored in awake head-fixed mice with a conditional microglia-specific ADF/Cfl1 knockout. Furthermore, to address how ADF/Cfl1-deficient microglia affect synapse remodeling, we will investigate dendritic spines and adjacent microglia in the hippocampus in vivo on the nanoscopic scale by cutting-edge 2P-STED microscopy. Supported by our preliminary data, we will provide not only novel insights on the role of ADF/Cfl1 in microglia, but also on physiological microglia-neuron interplay with regard to learning and memory.
DFG Programme
Priority Programmes
