Modulation of GABAergic transmission by activity via postsynaptic Ca 2+-dependent regulation of KCC2 function

Hubert Fiumelli, Laura Cancedda, Mu Ming Poo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

186 Scopus citations


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 (ECl) toward positive levels in a duration- and frequency-dependent manner. This effect was abolished by blocking cytosolic Ca2+ elevation and mimicked by releasing Ca2+ from internal stores. Activity- and Ca 2+-induced ECl 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 ECl, resulted in hyperpolarized ECl similar to that of mature cells. Importantly, these young KCC2-expressing neurons became responsive to neuronal spiking and Ca2+ elevation by showing positive ECl shifts. Thus, repetitive postsynaptic spiking reduces the inhibitory action of GABA through a Ca2+-dependent downregulation of KCC2 function.

Original languageEnglish (US)
Pages (from-to)773-786
Number of pages14
Issue number5
StatePublished - Dec 8 2005
Externally publishedYes

Bibliographical note

Funding Information:
We thank Hongfeng Gao for his help with the hippocampal cultures. This work was supported by grants from the National Institutes of Health (NS36999). H.F. was supported in part by a fellowship from the Swiss National Science Foundation.

ASJC Scopus subject areas

  • General Neuroscience


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