Effects of neurotrophins on the regulation of synaptic molecules and on the synaptic functions

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The aim of this project is the analysis of the action of neurotrophins, especially BDNF (brain-derived neurotrophic factors), on synaptic transmission and the elucidation of its molecular basis. The effects of BDNF is classified into 2 phases (acute or chronic)by its time window and also 2 categories depending on its site of action (pre- or post-synaptic). The results of the project in each categories are as follows.ACUTE ACTIONPre-Synapric : BDNF induced release of excitatory amino acid neurotroansmitters, glutamate and aspartate from cerebellar granule neurons in culture (Brain Res. 1999, Neurosci. Res. 2000). The signaling cascades which leaded to the release was revealed that BDNF-TrkB activation -PLC activation-Ca2+release from intracellular store-Na+ influx-reverse transport of glutamate/glutamate release (JNR.2000)Post-Synaptic : BDNF increased NMDA current and induced phosphorylation of NMBD receptor subunit. Both of them are mediated by Fynkinase, which activated by BDNF (presented at SFN meeting 2000).CHRONIC ACTIONPre-Synaptic : BDNF increased the expression of vesicular acetylcholine transporter and vesicular monoamine transporter2 in basalforebrain cholinergic and midbrain dopaminergic neurons, respectively (papers in preparation).Post-Synaptic : BDNF increased the levels of AMPA receptor subunit proteins and enhanced AMPA current, together with the induction of the some PDZ proteins which interacted with AMPA receptor (paper in preparation).