Abstract
The number of postsynaptic gamma-aminobutyric acid type A (GABAA) 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 GABAA receptors, through the activation of Trk B receptor tyrosine kinases. We also demonstrated that BDNF rapidly induced a sustained potentiation of GABAA 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-gamma. In addition, intracellular Ca2+ was important for the potentiation of GABAA 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 GABAA receptors in visual cortical pyramidal neurons. These results suggest that BDNF could alter the number of cell surface GABAA receptors in a region-specific manner.
Highlights
The number of postsynaptic ␥-aminobutyric acid type A (GABAA) receptors is a fundamental determinant of the variability of inhibitory synaptic responses in the central nervous system
The selective increase in mean miniature inhibitory postsynaptic (mIPSC) amplitude without effects on mIPSC time courses supports the idea that brain-derived neurotrophic factor (BDNF) rapidly induces an increase in the total number of cell surface functional GABAA receptors in visual cortical pyramidal neurons
Trk receptor tyrosine kinases [40, 41] to the BDNF-treated cells, blocked the elevation of [3H]SR-95531 binding. These results suggest that BDNF induced a rapid increase in the total number of cell surface GABAA receptors in rat visual cortex, through the activation of Trk B receptor tyrosine kinases
Summary
The number of postsynaptic ␥-aminobutyric acid type A (GABAA) receptors is a fundamental determinant of the variability of inhibitory synaptic responses in the central nervous system. 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 GABAA receptors in visual cortical pyramidal neurons. These results suggest that BDNF could alter the number of cell surface GABAA receptors in a region-specific manner. The elevation of intracellular Ca2ϩ levels, leading to the activation of protein kinases or phosphatases, either potentiates [3,4,5] or suppresses (6 – 8) the postsynaptic GABAA receptor responses These complex results suggest that region-specific phosphorylation or dephosphorylation processes regulate GABAergic function in a cell-specific manner. In hippocampus of postnatal day (P) 14 rat, BDNF acutely inhibits postsynaptic GABAA responses by elevating intracellular Ca2ϩ levels via the activation of Trk B receptor tyrosine kinase and subsequent phospholipase C (PLC) ␥ phosphorylation [13, 14], but at P6, BDNF reversibly potentiates postsynaptic GABAA responses [14]
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