BRAIN-DERIVED NEUROTROPHIC FACTOR ENHANCES LONG-TERM POTENTIATION IN RAT VISUAL-CORTEX

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), me mbers of the nerve growth factor (NGF) gene family, have been suggeste d to play a role in experience-dependent modification of neural networ ks in the developing nervous system. In this study we addressed the qu estion of whether these neurotrophins are involved in long-term potent iation (LTP) in developing visual cortex. We recorded layer II/III fie ld potentials and whole-cell currents evoked by test stimulation of la yer IV at 0.1 Hz in visual cortical slices prepared from young rats (p ost natal day 15-25) and observed effects of BDNF, NT-3, and NGF on th ese responses. Then we analyzed the effects of these neurotrophins on LTP induced by tetanic (Theta-burst type) stimulation of layer IV. We found that BDNF at 200 ng/ml potentiated field potentials and EPSCs in most cases and that this potentiation lasted after cessation of the B DNF application. At the concentration of 20 ng/ml, BDNF did not show s uch an effect, but it enhanced the magnitude of expressed LTP. On the other hand, NT-3 and NGF had none of these effects. Immunohistochemica l staining of slices with antibody against BDNF showed that exogenous BDNF penetrated into the whole slice within similar to 5 min of its ap plication. The actions of BDNF were blocked by preincubation of slices with TrkB-IgG fusion protein, a BDNF scavenger, or coapplication of K 252a, an inhibitor for receptor tyrosine kinases. TrkB-IgG or K252a it self completely blocked LTP, suggesting that endogenous BDNF or anothe r TrkB ligand plays a role in LTP in the developing visual cortex.