Approximately one-third of individuals with chronic epilepsy do not experience adequate effect from antiseizure medications. Given that epilepsy is a heterogeneous condition with diverse causes and potentially underlying mechanisms, more research on the basic mechanisms of seizures and epilepsy is needed. In this paper (1), Han-Tao Li et al. focus on the role of hypocretin/orexin neurons in the lateral hypothalamus (LH) in relation to seizures, utilizing a mouse model of epilepsy. These neurons are known to play a significant role in regulating sleep and wakefulness.
The authors used a mouse model of acute epilepsy and employed advanced neuroscience techniques, including fiber-optic recordings, electrophysiological recordings, deep brain stimulation, and optogenetic activation and silencing of specific types of neurons in their study. Their findings indicate that decreased activity in hypocretin/orexin neurons prior to seizure onset is associated with shorter and less intense seizures, while heightened activity correlates with more severe seizures.
The relationship was further explored through optogenetic silencing of the hypocretin/orexin neurons, which resulted in significant reductions in both the length and intensity of seizures. They also investigated the use of deep brain stimulation (DBS) to replicate these findings; again, suppressing the activity of hypocretin/orexin neurons prior to seizures led to marked decreases in seizure probability, intensity, and duration.
Overall, this study suggests that the lateral hypothalamus may play an important role in epileptic seizures and that this circuit could represent a potential target for epilepsy treatment.
Key Points:
- This study (1) investigates the role of hypocretin/orexin neurons in the lateral hypothalamus during epileptic seizures, using a mouse model of acute epilepsy.
- A notable correlation was identified between the activity of hypocretin/orexin neurons just prior to the onset of seizures and seizure probability, intensity, and duration.
- By using advanced techniques such as optogenetic silencing and deep brain stimulation, the researchers managed to silence the hypocretin/orexin neurons prior to seizures, resulting in a significant decrease in the probability, duration, and intensity of epileptic seizures.
References:
- Li, H. T., Viskaitis, P., Bracey, E., Peleg-Raibstein, D., & Burdakov, D. (2024). Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy. Nature Communications, 15(1), 1249.
Publish on behalf of the Coordinating Panel on Neuroscience/ Translational Neurology