| First Author | O'Sullivan GA | Year | 2016 |
| Journal | Mol Cell Neurosci | Volume | 72 |
| Pages | 101-13 | PubMed ID | 26829712 |
| Mgi Jnum | J:231924 | Mgi Id | MGI:5775506 |
| Doi | 10.1016/j.mcn.2016.01.010 | Citation | O'Sullivan GA, et al. (2016) Forebrain-specific loss of synaptic GABAA receptors results in altered neuronal excitability and synaptic plasticity in mice. Mol Cell Neurosci 72:101-13 |
| abstractText | Mutations that result in the defective trafficking of gamma2 subunit containing GABAA receptors (gamma2-GABAARs) are known to reduce synaptic inhibition. Whether perturbed clustering of non-mutated GABAARs similarly reduces synaptic inhibition in vivo is less clear. In this study we provide evidence that the loss of postsynaptic gamma2-GABAARs upon postnatal ablation of gephyrin, the major scaffolding protein of inhibitory postsynapses, from mature principal neurons within the forebrain results in reduced induction of long-term potentiation (LTP) and impaired network excitability within the hippocampal dentate gyrus. The preferential reduction in not only synaptic gamma2-GABAAR cluster number at dendritic sites but also the decrease in gamma2-GABAAR density within individual clusters at dendritic inhibitory synapses suggests that distal synapses are more sensitive to the loss of gephyrin expression than proximal synapses. The fact that these mice display behavioural features of anxiety and epilepsy emphasises the importance of postsynaptic gamma2-GABAAR clustering for synaptic inhibition. |
