Figure 1: The key role of p75NTR in the generation of DGy GNs. In this cheme, a neuro-trophin (BDNF or NGF) in the DGy SGZ activates cilial p75NTR, the signals from which stimulate progenitor cell proliferation and the generation of rapidly proliferating TA precursor neurons. After several rounds of proliferation, the TA precursor neurons stop proliferating and signals 6 from the cilial SSTR3 and BDNF•TrkB complexes stimulate them to mature, enter the granule cell layer and serve transiently as intensive long-term potentiation (LTP)- generating, super-sensitive encoders of novel multi-modal inputs flowing along the perforant pathway from the entorhinal cortex. Normally, half or more of the newborn cells may die without reaching the granule cell layer. But NGF produced in the DGy from proNGF by tPA-generated plasmin forms NGF•Trk A complexes that stimulate BFCSNs to make Ach and release it in the hippocampus, which promotes newborn neurons survival and thus neurogenesis and memory formation. Eventually, the successful neurons lose their hyper-responsiveness and become loaded with old ‘memories’, retire, and are replaced with new recorders.
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