title: Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses.
abstract: 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.
authors: Department of Neurosciences, University of Turin, and National Institute of Neuroscience-Italy, Torino, Italy.
authors: Elena
authors: E
authors: Frola
authors: Annarita
authors: A
authors: Patrizi
authors: Thomas
authors: T
authors: Goetz
authors: Lucian
authors: L
authors: Medrihan
authors: Enrica Maria
authors: EM
authors: Petrini
authors: Andrea
authors: A
authors: Barberis
authors: Peer
authors: P
authors: Wulff
authors: William
authors: W
authors: Wisden
authors: Marco
authors: M
authors: Sassoè-Pognetto
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D011963:Receptors, GABA-A / Q000172:deficiency / Q000235:genetics; D013569:Synapses / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C546280:Gabrg2 protein, mouse; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C098003:neuroligin 2; D005680:gamma-Aminobutyric Acid