Parvalbumin neurons in the anterior nucleus of thalamus control absence seizures

Abstract

ObjectiveAnterior nucleus of thalamus (ANT) has been widely accepted as a potential therapeutic target for drug‐resistant epilepsy. Although increased volume of the ANT was also reported in patients with absence epilepsy, the relationship between the ANT and absence epilepsy has been barely illustrated.MethodsUsing chemogenetics, we evaluated the effect of ANT parvalbumin (PV) neurons on pentylenetetrazole (PTZ)‐induced absence seizures in mice.ResultsWe 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.SignificanceOur 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.

Suppression of piriform cortex alters brain-wide dynamics and alleviates seizures in temporal lobe epilepsy

“…To our knowledge, this is the first report showing that activation of APC PV interneurons, hence suppressing APC activity, alleviates seizure activities in TLE. Our work corroborates and extends on the literature showing that PV neurons contributes to seizure symptoms 34–37 . As APC has extensive connection in the limbic circuitry, further work is warranted to precisely determine how APC output connections can initiate or propagate seizures and whether these manipulations induce side effects or not.…”

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

“…Animal models have played a significant role in understanding the mechanisms and treatment of human epilepsies [ 131 ]. Indeed, both acute pharmacological animal models [ 132 ] and chronic animal models [ 133 ] used in the study of absence epilepsy to gain a better understanding of the condition and to test potential treatments; AY-9944 and MAM-AY are indeed animal models used to study atypical absence seizures [ 134 ], and they are valuable tools for researchers working to understand the mechanisms underlying atypical absence seizures and explore potential treatments. The investigation of infantile spasms in animal models is recent and intriguing [ 135 , 136 ].…”