Increased thalamic inhibition in the absence seizure prone DBA/2J mouse

Genetic background plays a significant role in producing variable seizure outcomes in patients and animal models. The neurobiological mechanism underlying this heterogeneity is not clear. Here we compare GABAergic synaptic properties within the thalamocortical circuit of two commonly used inbred mice strains, the C57B/6 and spike-and-wave discharge (SWD) prone DBA/2J. Differences between the strains occur in amplitude, kinetics, and frequency of miniature inhibitory postsynaptic currents (mIPSCs) in a region-specific manner. The biggest difference in synaptic inhibition was seen in the thalamus where DBA/2J mice showed a doubling of mIPSC frequency when compared to C57B/6. EEG analysis revealed higher power in the 6-12 Hz band during non-rapid eye movement sleep in DBA/2J mice. Increased susceptibility of the DBA2/J strain to develop SWDs and increase in the 6-12 Hz EEG power may be due to a hypersynchronous ventrobasal thalamus as a consequence of increased GABAergic input.