Mechanisms underlying action of neurotrophic factors on postsynaptic glutamate and GABA receptors

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Previously we found that brain-derived neurotrophic factor (BDNF) is released from presynaptic sites in an activity-dependent manner and acts on postsynaptic neurons. In this study we attempted to see whether actions of BDNF are different between glutamatergic excitatory synapses and GABAergic inhibitory synapses, and further to elucidate mechanisms underlying such actions. We obtained the following results.1.Using mixed neuron culture preparations obtained from green fluorescence protein (GFP) mice and BDNF knockout mice, we explored what actions presynaptic BDNF exerts on postsynaptic neurons. We found that presynaptic BDNF promotes dendritic development of postsynaptic GABAergic neurons.2.Actions of exogenous BDNF on GABAergic synapses were investigated in solitary GABAergic neurons cultured on glial microisland to completely exclude possible involvement of excitatory synapses from the observed effects of BDNF. We found that BDNF increased the number of active GABAergic synapses.3.Roles of endogenous BDNF in development of glutamatergic synapses were investigated in barrel cortex of BDNF knockout and wild type mice. We found that silent synapses, which consist only of NMDA receptors, are abnormally increased in BDNF knockout mice, and this is rescued by exogenously applied BDNF.4.Actions of exogenous BDNF on excitatory synapses on GABAergic neurons were not studied previously. We addressed this issue by using GAD67-GFP knock-in mice, in which GABAergic neurons are easily identified. We found that BDNF acutely depressed function of excitatory synapses to GABAergic neurons.