Severity of atypical absence phenotype in GABAB transgenic mice is subunit specific

Overexpression of GABABR1a receptors in mice (R1a+) results in an atypical absence seizure phenotype characterized by 3- to 6-Hz slow spike-and-wave discharges (SSWDs), reduced synaptic plasticity, and cognitive impairment. Here we tested the hypothesis that increased R1 expression causes atypical absence epilepsy and is not subunit specific. GABABR1b receptors were overexpressed in mouse forebrain (R1b+) and confirmed by immunoblot and 3H-CGP54626A autoradiography. The R1b+ mice showed a reduction in hippocampal long-term potentiation and GABAA receptor-mediated inhibitory postsynaptic currents. R1b+ mice manifested an electrographic, pharmacological, and behavioral phenotype consistent with atypical absence seizures, though less robust than R1a+ in terms of SSWD duration and severity of cognitive impairment. These results suggest that abnormal GABABR1b function plays a lesser role in the development of atypical absence epilepsy.