The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons
The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons
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DOI：
10.1113/jphysiol.2003.038935
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发表时间：
2003-05-01
影响因子：
5.5
通讯作者：
Nabekura, J
中科院分区：
文献类型：
--
作者：
Mizoguchi, Y;Ishibashi, H;Nabekura, J
在海马发育过程中，GABA的作用由去极化向超极化转变，脑源性神经营养因子（BDNF）在GABA能传递中起重要作用。我们证明BDNF（20 ng ml（-1））快速可逆地增强海马CA 1区锥体神经元突触后GABA（A）受体介导的电流（增强80.5 +/-14.3%，n = 10），这些神经元分离自出生后6天（P）的大鼠，使用制霉菌素穿孔膜片阻尼记录。这种增强作用是由细胞内Ca 2+升高引起的，其响应于Trk B受体酪氨酸激酶和磷脂酶C-γ的活化而发生。BDNF对P10大鼠海马CA 1区锥体神经元GABAA反应的调节更为多样（从增强到抑制），在P14时，BDNF诱导了持久的抑制。此外，Ca ~（2+）/钙调素依赖性蛋白激酶2在增强BDNF对GABAA反应的作用中起重要作用，但在抑制作用中不起作用。这些结果表明，在细胞内信号通路的变化可能有助于发展的BDNF对抑制系统的行动转变。
During the development of the hippocampus, the action of GABA shifts from depolarizing to hyperpolarizing, and brain-derived neurotrophic factor (BDNF) has important roles in GABAergic transmission. We demonstrate that BDNF (20 ng ml(-1)) rapidly and reversibly potentiates postsynaptic GABA(A) receptor-mediated currents (by 80.5 +/- 14.3 %, n = 10) in hippocampal CA1 pyramidal neurons isolated from postnatal day (P)6 rats, using nystatin-perforated patch-damp recordings. This potentiation is caused by an elevation of intracellular Ca2+ that occurs in response to the activation of Trk B receptor tyrosine kinase and phospholipase C-gamma. The modulation of the GABAA responses by BDNF in hippocampal CAI pyramidal neurons isolated from P10 rats was more diverse (from potentiating to inhibitory), and at P14, BDNF induced a long-lasting inhibition. In addition, Ca2+/calmodulin-dependent protein kinase 2 plays important roles in the potentiating, but not in the inhibitory effect, of BDNF on the GABAA responses. These results suggest that changes in the intracellular signalling pathway could contribute to the developmental shift of the actions of BDNF on inhibitory systems.