Kazuhiro Yamakawa and his team at the RIKEN Center for Brain Science (CBS) in Japan has shown that absence epilepsy can be triggered by impaired communication between two brain regions: the cortex and the striatum.
The researchers took STXBP1 and SCN2A genes created mice with one normal gene and one mutated gene -- a condition called haplodeficiency, which is different from a complete knockout. They showed that Spike Wave Discharges (SWD) can be blocked by drugs than inhibit neurons from exciting each other. The scientists injected a neuronal inhibitor into several brain regions hoping to find which ones were related to the seizures. They found three regions: somatosensory cortex, the thalamus, and a part of the striatum beneath the cortex.
It is generally believed that the thalamus and the somatosensory cortex are the primary sources for absence seizures. However Yamakawa and his group's experiments indicate that the critical trigger for absence seizures lie in the striatum.
After finding that injecting a neuron-exciting drug only into the striatal region of the model mice reliably induced SWDs, they created mice with mutations limited to only neurons in the somatosensory cortex that were connected to the striatum. These mice showed the same SWDs, meaning that absence seizures were triggered by faulty signals arriving in the striatum. An additional experiment showed that the problem arose because transmission specifically to fast-spiking interneurons in the striatum was too weak.
These findings potentially represent a paradigm shift for epilepsy research
Hiroyuki Miyamoto, Tetsuya Tatsukawa, Atsushi Shimohata, Tetsushi Yamagata, Toshimitsu Suzuki, Kenji Amano, Emi Mazaki, Matthieu Raveau, Ikuo Ogiwara, Atsuko Oba-Asaka, Takao K. Hensch, Shigeyoshi Itohara, Kenji Sakimura, Kenta Kobayashi, Kazuto Kobayashi, Kazuhiro Yamakawa. Impaired cortico-striatal excitatory transmission triggers epilepsy. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-09954-9