Parvalbumin neurons in the anterior nucleus of thalamus control absence seizures.

Abstract

Anterior nucleus of thalamus (ANT) has been widely accepted as a potential therapeutic target for drug-resistant epilepsy. Although atrophy of the ANT was also reported in patients with absence epilepsy, the relationship between the ANT and absence epilepsy has been barely illustrated. Using chemogenetics, we evaluated the effect of ANT parvalbumin (PV) neurons on pentylenetetrazole (PTZ)-induced absence seizures in mice. We found that intraperitoneal injection of PTZ (30 mg/kg) can stably induce absence-like seizures characterized by bilaterally synchronous spike-wave discharges (SWDs). Selective activation of PV neurons in the ANT by chemogenetics could aggravate the severity of absence seizures, whereas selective inhibition of that cannot reverse this condition and even promote absence seizures as well. Moreover, chemogenetic inhibition of ANT PV neurons without administration of PTZ was also sufficient to generate SWDs. Analysis of background EEG showed that chemogenetic activation or inhibition of ANT PV neurons could both significantly increase the EEG power of delta oscillation in the frontal cortex, which might mediate the pro-seizure effect of ANT PV neurons. Our findings indicated that either activation or inhibition of ANT PV neurons might disturb the intrinsic delta rhythms in the cortex and worsen absence seizures, which highlighted the importance of maintaining the activity of ANT PV neurons in absence seizure.