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GABAB receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses

Nature Neuroscience volume 11, pages 1410–1418 (2008)Cite this article

Abstract

Activity-induced long-term modification of glutamatergic synapses depends on the frequency of synaptic activation. We found that long-term modification of developing rat hippocampal GABAergic synapses that was induced by repetitive coincident pre- and postsynaptic spiking was also frequency dependent. Spiking at 20–50 Hz resulted in synaptic potentiation, whereas spiking at 5 Hz led to synaptic depression. The potentiation was abolished by blocking GABAB receptors (GABABRs), whereas the depression was independent of GABABR activation and could be converted to potentiation by elevating GABABR activity. The potentiation could be attributed to a local postsynaptic increase in Na+/K+/2Cl− co-transporter activity near activated synapses. The activity of postsynaptic Ca2+/calmodulin-dependent protein kinase II was necessary for long-term potentiation of these developing GABAergic synapses and its phosphorylation at Thr286 could be enhanced by activating GABABRs with baclofen. Together with our finding that activation of GABABRs is frequency dependent, these results indicate that postsynaptic GABABR activation mediates frequency-dependent potentiation of developing GABAergic synapses.

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Figure 1: Coincident pre- and postsynaptic spiking potentiates GABAergic synapses.
Figure 2: Activation of both GABAARs and GABABRs is required for LTP induction.
Figure 3: Frequency-dependent activation of GABABR-mediated postsynaptic currents.
Figure 4: Effects of GABABR activation on spiking frequency–dependent plasticity.
Figure 5: Postsynaptic expression of GABAergic synaptic modification.
Figure 6: NKCC1 is required for synaptic potentiation.
Figure 7: Postsynaptic Ca2+ elevation and CaMKII activity are required for synaptic potentiation.

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Acknowledgements

We thank Y. Xiang, W.P. Ge, H. Lu, Q.S. Liu, H.K. Wang, X.W. Cheng, J.M. Jia and X.P. Zhou for technical help and discussion, and Huang Z.J. for comments on the manuscript. This work was supported by grants from the National Basic Research Program of China (2006CB806600 and 2006CB943900). M.-m.P. was supported in part by a grant from the US National Institutes of Health (NS 36999). X.-h.Z. was supported by an International Human Frontier Science Program Career Development Award.

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Authors and Affiliations

  1. Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031, China

    Chun Xu, Man-xia Zhao, Mu-ming Poo & Xiao-hui Zhang

  2. Division of Neurobiology, Department of Molecular & Cell Biology, Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, 221 LSA, 94720, California, USA

    Mu-ming Poo

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  1. Chun Xu
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C.X. designed and conducted electrophysiology recording experiments and wrote the manuscript. M.-x.Z. conducted the western blot experiments. M.-m.P. and X.-h.Z. supervised the project and wrote the manuscript.

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Correspondence to Mu-ming Poo or Xiao-hui Zhang.

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Xu, C., Zhao, Mx., Poo, Mm. et al. GABAB receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses. Nat Neurosci 11, 1410–1418 (2008). https://doi.org/10.1038/nn.2215

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