Impacted spike frequency adaptation associated with reduction of KCNQ2/3 exacerbates seizure activity in temporal lobe epilepsy.

Numerous epilepsy-related genes have been identified in recent decades by unbiased genome-wide screens. However, the available druggable targets for temporal lobe epilepsy (TLE) remain limited. Furthermore, a substantial pool of candidate genes potentially applicable to TLE therapy awaits further validation. In this study, we reveal the significant role of KCNQ2 and KCNQ3, two M-type potassium channel genes, in the onset of seizures in TLE. Our investigation began with a quantitative analysis of two publicly available TLE patient databases to establish a correlation between seizure onset and the downregulated expression of KCNQ2/3. We then replicated these pathological changes in a pilocarpine seizure mouse model and observed a decrease in spike frequency adaptation due to the affected M-currents in dentate gyrus granule neurons. In addition, we performed a small-scale simulation of the dentate gyrus network and confirmed that the impaired spike frequency adaptation of granule cells facilitated epileptiform activity throughout the network. This, in turn, resulted in prolonged seizure duration and reduced interictal intervals. Our findings shed light on an underlying mechanism contributing to ictogenesis in the TLE hippocampus and suggest a promising target for the development of antiepileptic drugs.

[Effects of olfactory deprivation on action potential and ankyrin-G expression in glutamatergic neurons in the barrel cortex of mice].

OBJECTIVE: To investigate effect of upregulated touch sensation induced by olfactory deprivation on action potentials and ankyrin-G expression in the glutamatergic neurons in the barrel cortex of mice. METHODS: Chloroform (40 µL) was dropped into the unilateral nasal cavity to induce olfactory deprivation in 40 C57 mice (12 days old), whose glutamatergic neurons were genetically labeled with yellow fluorescent protein (YFP). Behavioral experiments were carried out to assess the effects of olfactory deprivation on whisker tactile of the mice. The action potentials of the glutamatergic neurons in the barrel cortex on the side with or without chloroform treatment (olfactory deprivation group and control group, respectively) were recorded by patch-clamp electrophysiological recording, and ankyrin-G expression in the proximal axonal segment of the neurons was detected with immunohistochemistry. RESULTS: Compared with those on the control side, the inter-spike intervals of the barrel glutamatergic neurons were significantly decreased and the absolute refractory periods were significantly shortened on the side with olfactory deprivation (P < 0.01); the expression of ankyrin-G was also significantly increased in the proximal axonal segment of the glutamatergic neurons in the barrel cortex on the side with olfactory deprivation (P < 0.01). CONCLUSIONS: Olfaction deprivation induces up-regulation of touch sensation in mice possibly as a result of functional enhancement of the glutamatergic neurons and increased ankyrin-G expression in the barrel cortex.