GABAA receptors constitutively enter and exit synapses by lateral diffusion in the plane of the neuronal membrane. They are trapped at synapses through their interactions with @entity68601 , the main scaffolding protein at inhibitory post-synaptic densities. Previous work has shown that the synaptic accumulation and diffusion dynamics of GABAARs are controlled via excitatory synaptic activity. However, it remains unknown whether @entity22099 activity can itself impact the surface trafficking of the receptors. Here we report the effects of @entity22099 agonists, antagonists and allosteric modulators on the receptor's surface dynamics. Using immunocytochemistry and single particle tracking experiments on @entity19 hippocampal neurons, we show that the agonist @entity6341 decreases @entity22099 and @entity68601 levels at synapses and accelerates the receptor's lateral diffusion within 30-120min of treatment. In contrast, the @entity22099 antagonist @entity8772 increased @entity22099 amounts and slowed down @entity22099 diffusion at synapses. The response to @entity22099 activation or inhibition appears to be an adaptative regulation of GABAergic synapses. Surprisingly, the positive allosteric modulator @entity3175 abolished the regulation induced by @entity6341 , and this effect was observed on a1, a2, a5 and y2 @entity22099 subunits. Altogether these results indicate that @entity3175 stabilizes synaptic GABAARs and thus prevents the agonist-induced regulation of @entity22099 levels at synapses. This occurred independently of neuronal activity and intracellular @entity460 and involved @entity22099 - @entity68601 interactions, suggesting that the changes in @entity22099 diffusion depend on conformational changes of the receptor. Our study provides a new molecular mechanism involved in the adaptative response to changes in @entity22099 activity and @entity1245 treatments.

XXXX -dependent stabilization of GABAA receptors at synapses.

@entity6341 :: ('MESH:D009118', 'Chemical') :: ['muscimol'] @entity3175 :: ('MESH:D003975', 'Chemical') :: ['diazepam'] @entity68601 :: ('268566(Tax:10090)', 'Gene') :: ['gephyrin'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity1245 :: ('MESH:D001569', 'Chemical') :: ['benzodiazepine'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity8772 :: ('MESH:C049853', 'Chemical') :: ['gabazine'] @entity22099 :: ('14406(Tax:10090)', 'Gene') :: ['GABAAR']
@entity1245 :: (MESH:D001569,Chemical) :: ['Benzodiazepine']
