Forebrain-specific loss of synaptic GABAA receptors results in altered neuronal excitability and synaptic plasticity in mice
| Autor: | Yannis Kalaidzidis, Stephan W. Schwarzacher, Hong-Xing Chen, Peter Jedlicka, Heba Kalbouneh, Gregory A. O'Sullivan, Jochen Kuhse, Ralph Nawrotzki, Angelo Ippolito, Heinrich Betz, Joachim Kirsch, Thomas Deller |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Long-Term Potentiation Inhibitory postsynaptic potential Cell Line 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Prosencephalon Synaptic augmentation Metaplasticity Animals Molecular Biology Neuronal memory allocation Neurons Gephyrin biology Membrane Proteins Long-term potentiation Cell Biology Synaptic Potentials Receptors GABA-A Mice Inbred C57BL 030104 developmental biology Synaptic fatigue Synaptic plasticity Dentate Gyrus Synapses biology.protein Carrier Proteins Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecular and cellular neurosciences. 72 |
| ISSN: | 1095-9327 |
| Popis: | Mutations that result in the defective trafficking of γ2 subunit containing GABAA receptors (γ2-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 γ2-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 γ2-GABAAR cluster number at dendritic sites but also the decrease in γ2-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 γ2-GABAAR clustering for synaptic inhibition. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect