Atlastin-1 modulates seizure activity and neuronal excitability

Epilepsy is a neurological disease, and the main clinical manifestation is recurrent seizures. The exact etiology of epilepsy and the pathogenesis of the disorder are not yet fully understood. Atlastin-1, a dynamin-like GTPase, interacts with microtubules and is responsible for vesicle formation, both of which are highly associated with the development of epilepsy. Here, we reported that the expression level of atlastin-1 protein was reduced in the temporal neocortex of patients with temporal lobe epilepsy and in the hippocampus and adjacent cortex of a pentylenetetrazol-kindled epileptic mouse model. Cells expressing atlastin-1 coexpressed the inhibitory synaptic marker GAD67 in the temporal cortex and hippocampus of patients with epilepsy and an epileptic mouse model. The lentivirus-mediated overexpression of atlastin-1 protein in the hippocampus of mice suppressed seizure activity in behavioral experiments. Patch-clamp recordings in the Mg²⁺ -free epilepsy cell model showed that atlastin-1 overexpression inhibited neuronal excitability by suppressing the discharge frequency of spontaneous action potentials rather than by changing the passive and active properties of action potentials. Inhibitory synaptic transmission, but not excitatory synaptic currents, increased after atlastin-1 overexpression. These findings suggest that atlastin-1 likely contributes to the occurrence and development of epilepsy through inhibitory synaptic transmission.