5.2 What is the neuronal circuit basis of histaminergic system in epilepsy?
According to the electrographic feature, the epileptic seizure is usually composed of a beginning, a middle and an end, which is associated with seizure initiation, propagation, and termination (Bertram, 2013). There are different neural networks involved in each stage (Wang & Chen, 2019). It is well known that the histaminergic fibers widely project in the brain. Histaminergic system participates in particular one period or the whole process is obscured. Given an example, the nucleus of solitary tract shows an promising neuroprotective role in patients with poorly controlled epilepsy (Cakmak, 2006). It has reported that the histaminergic input from TMN to the solitary tract nucleus participating in arterial pressure regulation (Yamanaka, Gouraud, Takagishi, Kohsaka, Maeda & Waki, 2017). Whether the TMN-solitary tract histaminergic projection regulates epilepsy needs validate further.
Interestingly, although histamine and several histamine receptors receive positive response in epileptic seizure, DBS directly on TMN showed a dominant protection accompanying with a prominent increase of histamine release in the frontal cortex after TMN stimulation in PTZ rats (Nishida, Huang, Mikuni, Miura, Urade & Hashimoto, 2007). However, LFS of the TMN had no appreciable effects in PTZ model (Wu et al., 2008). LFS of the TMN accelerated seizure stage and increased the mean afterdischarge duration (ADD) during acquisition but had no anticonvulsive effect in fully kindled, HFS and bilateral lesions of TMN exacerbated the seizure progression in the amygdaloid kindling (Wu et al., 2008). These finding supports that DBS on TMN is not a good therapeutic approach to control seizure. Advanced technologies, such as novel optogenetics (Kim, Adhikari & Deisseroth, 2017), in combination with novel viral tracing system (Nectow & Nestler, 2020; Xu et al., 2020), provide high temporal and spatial specificity to reveal the circuit basis of histaminergic system in epilepsy.