NERVE GROWTH-FACTOR AND BRAIN-DERIVED NEUROTROPHIC FACTOR INCREASE NEUROTRANSMITTER RELEASE IN THE RAT VISUAL-CORTEX

A number of experiments have shown that neurotrophins are involved in the development and plasticity of the visual cortex (Bonhoeffer, T., C urr. Op. Neurobiol., 6, 119, 1996), A possible mechanism underlying th ese effects is the neurotrophin modulation of synaptic transmission. W e investigated whether nerve growth factor (NGF) and brain-derived neu rotrophic factor (BDNF) can modulate the release of neurotransmitter i n the rat visual cotter at the peak of the critical period for plastic ity (P23), The release of glutamate, acetylcholine and gamma-aminobuty ric acid (GABA) from visual cortical synaptosomes was analysed in cont inuous perfusion conditions. We found that NGF enhances the depolariza tion-evoked release of glutamate (approximate to 90%) and acetylcholin e (approximate to 35%) but not that of GABA, By contrast, BDNF enhance s the depolarization-evoked release of all three neurotransmitters inv estigated (approximate to 30%), BDNF and NGF were ineffective on basal release of neurotransmitters. The effect of NGF was not blocked by ch olinergic antagonists atropine and mecamylamine, NGF and BDNF potentia tion of transmitter release was strongly but not completely blocked by K252a, a tyrosine kinase inhibitor. The role of TrkA and p75(NTR) rec eptors was investigated in NGF-induced potentiation of glutamate relea se. Block of NGF binding to p75(NTR) using specific blocking antibodie s (REX-IgG) slightly but significantly reduced the effect of NGF, Acti vation of TrkA in isolation by RTA-IgG, an antibody that specifically activates TrkA, was less effective than activation of both receptors b y NGF, These results show that neurotrophin action on neurotransmitter release was mostly mediated by Trk receptors with p75(NTR) having a l ittle but significant positive role. Antigen blot analysis showed the presence of TrkA, TrkB and p75(NTR) receptors in the visual cortex.