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.