The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABA receptors (GABARs) 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 GABAR γ2 subunit gene which produced a mosaic expression of synaptic GABARs 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 GABARs. 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 GABARs from all Purkinje cells, were rare in cerebella of γ2 knockdown mice. These findings reveal a selective role of γ2 subunit-containing GABARs 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.

Synaptic competition sculpts the development of GABAergic axo-dendritic but not perisomatic synapses.

FROLA, ELENA;PATRIZI, Annarita;SASSOE' POGNETTO, Marco
2013-01-01

Abstract

The neurotransmitter GABA regulates many aspects of inhibitory synapse development. We tested the hypothesis that GABA receptors (GABARs) 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 GABAR γ2 subunit gene which produced a mosaic expression of synaptic GABARs 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 GABARs. 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 GABARs from all Purkinje cells, were rare in cerebella of γ2 knockdown mice. These findings reveal a selective role of γ2 subunit-containing GABARs 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.
2013
8
2
e56311
e56311
GABA-A receptor; neuroligin; Synaptic development; Purkinje cell; Receptor clustering
E. Frola; A. Patrizi; T. Goetz; L. Medrihan; E.M. Petrini; A. Barberis; P. Wulff; W. Wisden; M. Sassoè-Pognetto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/129007
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