Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses.
The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs) work together with the synaptic adhesion molecule neuroligin 2 (NL2) to regulate synapse formation in different subcellular compartments. We investigated mice (...
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056311&type=printable |
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| author | Elena Frola Annarita Patrizi Thomas Goetz Lucian Medrihan Enrica Maria Petrini Andrea Barberis Peer Wulff William Wisden Marco Sassoè-Pognetto |
| author_facet | Elena Frola Annarita Patrizi Thomas Goetz Lucian Medrihan Enrica Maria Petrini Andrea Barberis Peer Wulff William Wisden Marco Sassoè-Pognetto |
| author_sort | Elena Frola |
| collection | DOAJ |
| description | The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs) work together with the synaptic adhesion molecule neuroligin 2 (NL2) to regulate synapse formation in different subcellular compartments. We investigated mice ("γ2 knockdown mice") with an engineered allele of the GABAAR γ2 subunit gene which produced a mosaic expression of synaptic GABAARs in neighboring neurons, causing a strong imbalance in synaptic inhibition. Deletion of the γ2 subunit did not abolish synapse formation or the targeting of NL2 to distinct types of perisomatic and axo-dendritic contacts. Thus synaptic localization of NL2 does not require synaptic GABAARs. However, loss of the γ2 subunit caused a selective decrease in the number of axo-dendritic synapses on cerebellar Purkinje cells and cortical pyramidal neurons, whereas perisomatic synapses were not significantly affected. Notably, γ2-positive cells had increased axo-dendritic innervation compared with both γ2-negative and wild-type counterparts. Moreover heterologous synapses on spines, that are found after total deletion of GABAARs from all Purkinje cells, were rare in cerebella of γ2 knockdown mice. These findings reveal a selective role of γ2 subunit-containing GABAARs in regulating synapse development in distinct subcellular compartments, and support the hypothesis that the refinement of axo-dendritic synapses is regulated by activity-dependent competition between neighboring neurons. |
| format | Article |
| id | doaj-art-863f60dbe04849b7a10bb3bb81ff1382 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-863f60dbe04849b7a10bb3bb81ff13822025-08-20T03:25:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5631110.1371/journal.pone.0056311Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses.Elena FrolaAnnarita PatriziThomas GoetzLucian MedrihanEnrica Maria PetriniAndrea BarberisPeer WulffWilliam WisdenMarco Sassoè-PognettoThe neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABAA receptors (GABAARs) work together with the synaptic adhesion molecule neuroligin 2 (NL2) to regulate synapse formation in different subcellular compartments. We investigated mice ("γ2 knockdown mice") with an engineered allele of the GABAAR γ2 subunit gene which produced a mosaic expression of synaptic GABAARs in neighboring neurons, causing a strong imbalance in synaptic inhibition. Deletion of the γ2 subunit did not abolish synapse formation or the targeting of NL2 to distinct types of perisomatic and axo-dendritic contacts. Thus synaptic localization of NL2 does not require synaptic GABAARs. However, loss of the γ2 subunit caused a selective decrease in the number of axo-dendritic synapses on cerebellar Purkinje cells and cortical pyramidal neurons, whereas perisomatic synapses were not significantly affected. Notably, γ2-positive cells had increased axo-dendritic innervation compared with both γ2-negative and wild-type counterparts. Moreover heterologous synapses on spines, that are found after total deletion of GABAARs from all Purkinje cells, were rare in cerebella of γ2 knockdown mice. These findings reveal a selective role of γ2 subunit-containing GABAARs in regulating synapse development in distinct subcellular compartments, and support the hypothesis that the refinement of axo-dendritic synapses is regulated by activity-dependent competition between neighboring neurons.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056311&type=printable |
| spellingShingle | Elena Frola Annarita Patrizi Thomas Goetz Lucian Medrihan Enrica Maria Petrini Andrea Barberis Peer Wulff William Wisden Marco Sassoè-Pognetto Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses. PLoS ONE |
| title | Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses. |
| title_full | Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses. |
| title_fullStr | Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses. |
| title_full_unstemmed | Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses. |
| title_short | Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses. |
| title_sort | synaptic competition sculpts the development of gabaergic axo dendritic but not perisomatic synapses |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0056311&type=printable |
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