| Title | Neuroligin-2 accelerates GABAergic synapse maturation in cerebellar granule cells. | | Author(s) | Fu Z, Vicini S | | Institution | Department of Psychiatry, Box 3209, Duke University Medical Center, 401I Bryan Research Building, Research Drive, Durham, NC 27710. | | Source | Mol Cell Neurosci 2009 May 19. | | Abstract | Neuroligins (NLGs) are postsynaptic cell adhesion molecules that are thought to function in synaptogenesis. To investigate the role of NLGs on synaptic transmission once the synapse is formed, we transfected neuroligin-2(NLG2) in cultured mouse cerebellar granule cells (CGCs), and recorded GABA(A) (gamma-aminobutyric acid) receptor mediated miniature postsynaptic currents (mISPCs). NLG2 transfected cells had mIPSCs with faster decay than matching GFP expressing controls at young culture ages (days in vitro, DIV 7-8). Down-regulation of NLG2 by the isoform specific shRNA-NLG2 resulted in an opposite effect. We and others have shown that the switch of alpha subunits of GABA(A) Rs from alpha2/3 to alpha1 underlies developmental speeding of the IPSC decay in various CNS regions, including the cerebellum. To assess whether the reduced decay time of mIPSCs by NLG2 is due to the recruitment of more alpha1 containing GABA(A)Rs at the synapses, we examined the prolongation of current decay by the zolpidem, which has been shown to preferentially enhance the activity of alpha1 subunit containing GABA channel. The application of zolpidem resulted in a significantly greater prolongation kinetics of synaptic currents in NLG2 over-expressing cells than control cells, suggesting that NLG2 over-expression accelerates synapse maturation by promoting incorporation of the alpha1 subunit-containing GABA(A)Rs at postsynaptic sites in immature cells. In addition, the effect of NLG2 on the speeding of decay time course of synaptic currents was abolished when we used CGC cultures from alpha1-/- mice. Lastly, to exclude the possibility that the fast decay of mIPSCs induced by NLG2 could be also due to the impacts of NLG2 on the GABA transient in synaptic cleft, we measured the sensitivity of mIPSCs to the fast-off competitive antagonists TPMPA. We found that TPMPA similarly inhibits mIPSCs in control and NLG2 over-expressing CGCs both at young age (DIV8) and old age (DIV14) of cultures. However, we confirm our previous finding of a greater inhibition of mIPSCs in young (DIV8) than more mature (DIV14) cultures. Together, our results suggest that NLG2 does not alter uniquantal GABA release, and the fast decay of mIPSC induced by NLG2 is due to the differential expression of postsynaptic GABA(A) receptor subtypes. Taken all together, we propose that NLG-2 plays important functional role in inhibitory synapse development and maturation. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19463950 |
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