Role of brain-derived neurotrophic factor (BDNF) in learning and memory

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We investigated cellular mechanisms by which brain-derived neurotrophic factor (BDNF) facilitates learning and memory. Our findings indicated that (1) Spatial memory formation in an 8-arm radial arm maze is associated with an increase in the mRNA levels of BDNF and its receptor TrkB phosphorylation in the hippocampus. (2) Continuous intracerebroventricular infusion of antisense BDNF oligonucleotide inhibited the processes of spatial memory acquisition as well as memory retention and/or retrival. (3) Activation of PI3-K/Akt signaling pathway and new protein synthesis is associated with BDNF-dependent learning and memory. (4) Interaction between BDNF/TrkB signaling and NMDA receptors via a src-family tyrosine kinase Fyn is also important for spatial memory formation.These results suggest that BDNF plays a crucial role in spatial memory formation and maintenance by activating new protein synthesis and NMDA receptors in the hippocampus, via TrkB/PI3-K/Akt and TrkB/Fyn/NR2B signaling pathways, respectively.Furthermore, we obtained some data regarding neural mechanism of spatial memory : (1)The CA3 region of the hippocampus is obligatory for spatial memory formation in the radial arm maze. (2) The activation of PKA/CREB signaling pathway in the hippocampus plays an important role in spatial memory formation in the radial arm maze. (3) A novel learning and memory task using an 8-arm radial arm maze was developed and characterized. (4) Direct infusion of p-amyloid or okadaic acid into the brain induces learning and memory impairment.