Mechanism of GABA B receptor‐induced BDNF secretion and promotion of GABA A receptor membrane expression

J. Neurochem. (2011) 118 , 533–545. Abstract Recent studies have shown that GABA B receptors play more than a classical inhibitory role and can function as an important synaptic maturation signal early in life. In a previous study, we reported that GABA B receptor activation triggers secretion of brain‐derived neurotrophic factor (BDNF) and promotes the functional maturation of GABAergic synapses in the developing rat hippocampus. To identify the signalling pathway linking GABA B receptor activation to BDNF secretion in these cells, we have now used the phosphorylated form of the cAMP response element‐binding protein as a biological sensor for endogenous BDNF release. In the present study, we show that GABA B receptor‐induced secretion of BDNF relies on the activation of phospholipase C, followed by the formation of diacylglycerol, activation of protein kinase C, and the opening of L‐type voltage‐dependent Ca 2+ channels. We further show that once released by GABA B receptor activation, BDNF increases the membrane expression of β 2/3 ‐containing GABA A receptors in neuronal cultures. These results reveal a novel function of GABA B receptors in regulating the expression of GABA A receptor through BDNF‐tropomyosin‐related kinase B receptor dependent signalling pathway.