Modulation of GABAergic transmission by activity via postsynaptic Ca2+-dependent regulation of KCC2 function.
摘要:
Activity-induced modification of GABAergic transmission contributes to the plasticity of neural circuits. In the present work we found that prolonged postsynaptic spiking of hippocampal neurons led to a shift in the reversal potential of GABA-induced Cl − currents (E Cl) toward positive levels in a duration- and frequency-dependent manner. This effect was abolished by blocking cytosolic Ca 2+ elevation and mimicked by releasing Ca 2+ from internal stores. Activity- and Ca 2+-induced E Cl shifts were larger in mature neurons, which express the K-Cl cotransporter KCC2 at high levels, and inhibition of KCC2 occluded the shifts. Overexpression of KCC2 in young cultured neurons, which express lower levels of KCC2 and have a more positive E Cl, resulted in hyperpolarized E Cl similar to that of mature cells. Importantly, these young KCC2-expressing neurons became responsive to neuronal spiking and Ca 2+ elevation by showing positive E Cl shifts. Thus, repetitive postsynaptic spiking reduces the inhibitory action of GABA through a Ca 2+-dependent downregulation of KCC2 function.
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DOI:
10.1016/j.neuron.2005.10.025
被引量:
年份:
2005






























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