Activation of lateral septum dorsal GABAergic neurons alleviates epilepsy in mice

Temporal lobe epilepsy (TLE) represents a common neurological disorder characterized by seizures arising from imbalances between neuronal excitation and inhibition (E-I). Correction of such imbalances has been shown to influence epileptogenesis. The hippocampal CA3 region possesses a high density of kainate receptors (KARs), implicated in the induction of epileptic seizures, and contains a high density of pyramidal neurons. Moreover, the lateral septum dorsal (LSD) is densely populated with GABAergic neurons. These two neuronal populations are closely interconnected. Thus, investigating neural circuits associated with CA3 is essential for understanding the mechanisms underlying TLE. This study aimed to examine the functional interactions between the LSD and CA3 neural circuits, explore the correlation between TLE and calcium dynamics in LSD-GABAergic and CA3 pyramidal neurons, and evaluate the effect of optogenetic activation of LSD-GABAergic neurons on seizure suppression. We identified bidirectional projections between the LSD and CA3, with direct projections from LSD-GABAergic neurons to CA3 pyramidal neurons. Notably, alterations in neuronal calcium signaling were correlated with the severity of TLE, and optogenetic activation of LSD-GABAergic neurons significantly attenuated seizure phenotypes in mice.