GABA_A receptors (GABA_ARs) form the major inhibitory system in the CNS. Many pathological disorders result from an imbalance in excitation and inhibition, for example, the heterozygous γ2 knockout displays increased anxiety-like behavior (Crestani et al., 1999). Furthermore, several mutations in GABA_AR subunit genes (α1, δ and γ2) are associated with the presentation of seizures in families with inherited epilepsies (reviewed by Mizielinska et al., 2006). GABA_ARs that are assembled from a combination of the different subunits (19 subunit genes plus splice variants) exhibit distinct pharmacological profiles and contribute to different aspects of the behavioural responses to benzodiazepines (reviewed by Wafford et al., 2004). The dynamic trafficking of excitatory receptors is pivotal in the formation of learning and memory. This study utilizes individually tagged wild type and mutant subunits in combination with in vitro neuronal models of epilepsy and ischaemia to analyze the dynamic movement of GABA_AR subunits. The use of pH-sensitive fluorophores permits visualization of endocytosis by the quenching of fluorescence on internalization into acidic vesicles. Previous findings have shown a down-regulation of the γ2-subunit after one hour of epileptiform activity using immunohistological techniques (Blair et al., 2004). Our approach is to monitor the actual time course of subunit trafficking following the onset of seizure-like activity and ischaemia.