A team led by Associate Professor Li Xuhui and Professor Zhuo Min from Xi'an Jiaotong University (XJTU)'s Frontier Institute of Science and Technology has made notable progress in epilepsy research, focusing on the role of cortical glutamate receptors.

Epilepsy, a neurological disorder affecting 50 million people globally, lacks effective treatments for many patients, with current drugs often having significant side effects.

The team focused on the role of Kainatereceptors (KAR), a type of ionotropic glutamate receptor known to play an essential role in synaptic transmission and plasticity, in epilepsy regulation. Although previous studies have used Kainic acid (KA), a glutamate analog, to induce epileptic seizures, the precise role of KAR in epilepsy remained unclear. Additionally, while the Anteriorcingulatecortex (ACC) and striatum are involved in epilepsy, the involvement of KAR receptors in ACC-striatal projection circuits has not been fully explored.

Using advanced techniques like whole-brain imaging (VISoR), patch-clamp electrophysiology, behavioral studies, pharmacology, opto- and chemogenetics, and calcium imaging, the research team discovered a direct glutamatergic excitatory synaptic transmission between the ACC and striatum. In both in vitro and in vivo epilepsy models, they found that KAR-mediated synaptic transmission was significantly upregulated, with the GluK1 subtype and adenylate cyclase AC1 playing key roles in this process. Inhibition of ACC activity or ACC-striatal projections significantly reduced seizure behaviors in pentylenetetrazol-induced epilepsy models. Furthermore, the administration of GluK1 receptor antagonist UBP310 or AC1 inhibitor NB001 showed notable antiepileptic effects.

The study, recently published in Advanced Science, was led by Li, with Zhuo as the corresponding author.