A Rapid Increase in the Total Number of Cell Surface Functional GABA _A Receptors Induced by Brain-derived Neurotrophic Factor in Rat Visual Cortex

The number of postsynaptic γ-aminobutyric acid type A (GABA _A) receptors is a fundamental determinant of the variability of inhibitory synaptic responses in the central nervous system. In rat visual cortex, [³H] SR-95531 binding assays revealed that brain-derived neurotrophic factor (BDNF), one of the neurotrophins, induced a rapid increase in the total number of cell surface GABA_A receptors, through the activation of Trk B receptor tyrosine kinases. We also demonstrated that BDNF rapidly induced a sustained potentiation of GABA_A receptor-mediated currents, using nystatin-perforated patch clamp recordings, in visual cortical layer 5 pyramidal neurons freshly isolated from P14 rats. The potentiation was caused by the activation of Trk B receptor tyrosine kinase and phospholipase C-γ. In addition, intracellular Ca²⁺ was important for the potentiation of GABA_A responses induced by BDNF. The selective increase in mean miniature inhibitory postsynaptic (mIPSC) current amplitude without effects on mIPSC time courses supports the idea that BDNF rapidly induces an increase in the total number of cell surface functional GABA _A receptors in visual cortical pyramidal neurons. These results suggest that BDNF could alter the number of cell surface GABA_A receptors in a region-specific manner.