Geon The Role of CRMP2 in Mossy Fiber Sprouting Papers



In the hippocampus, the axons projecting from dentate gyrus (DG) to CA3 are known as mossy fibers. Mossy fiber sprouting refers to the abnormal wiring of mossy fibers. Instead of branching out to neurons in the dentate hilus, mossy fibers connect to the dentate inner molecular layer. Its underlying mechanism remains unclear. This paper shows that the mossy fiber sprouting can be explained by the same principle as the formation of enduring memory (Paper 21). Namely, axon branches will grow toward dendritic filopodia. The initial seizure attack may cause significant loss of mossy cells and generate filopodia on the basal dendrites of dentate granule cells, corresponding to the inner molecular layer. Subsequent neural activities may activate mTOR to produce CRMP2 which plays a central role in axonal branching and outgrowth. In the absence of mossy cells and the presence of abundant filopodia in the inner molecular layer, the mossy fiber branches would make abnormal connections. This mechanism is supported by mounting evidence that activation of mTOR promotes mossy fiber sprouting and the direct evidence that the CRMP2 expression level correlates with the extent of mossy fiber sprouting. It can also explain why BDNF promotes mossy fiber sprouting, but BDNF knockout does not inhibit mossy fiber sprouting.


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