Abstract
Synaptogenesis and the role of dendritic protrusions in this process are well studied in glutamatergic synapses. Much less is known about the formation of GABAergic synapses, which are located predominantly on the dendritic shaft. We used genetically labeled interneurons in mature hippocampal slice cultures and two-photon laser-scanning microscopy to examine contact formation between GABAergic axons and the dendrites of CA1 pyramidal cells. Dendritic protrusions distinguished and selected between glutamatergic and GABAergic boutons. In contrast with contacts with glutamatergic boutons, which can be long lasting, the contacts of dendritic protrusions with GABAergic boutons were always short lived. Similarly, the contacts made by GABAergic axonal protrusions were always transient. New putative GABAergic synapses were formed exclusively by new boutons appearing at pre-existing axon-dendrite crossings without the involvement of any dendritic or axonal protrusions. These findings imply that fundamentally different mechanisms underlie the generation of GABAergic and glutamatergic synapses.
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Acknowledgements
We would like to thank G. Szábo for kindly providing the GAD65-GFP mice, U.V. Nägerl for help with the experimental setup and comments on the manuscript, N. Stöhr and C. Huber for technical assistance, and T. Mrsic-Flögel, C. Lohmann and V. Stein for critical reading of the manuscript. This work was supported by the Max Planck Gesellschaft, the Alexander von Humboldt Stiftung, a Marie Curie Intra-European fellowship (C.J.W.) and the Boehringer Ingelheim Fonds (N.B.).
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C.J.W. designed and conducted the experiments and analyzed the data. N.B. carried out the experiments on glutamatergic boutons. C.J.W. and T.B. conceived the project and wrote the manuscript.
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Wierenga, C., Becker, N. & Bonhoeffer, T. GABAergic synapses are formed without the involvement of dendritic protrusions. Nat Neurosci 11, 1044–1052 (2008). https://doi.org/10.1038/nn.2180
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DOI: https://doi.org/10.1038/nn.2180
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