Medial septal (MS) glutamatergic neurons expressing type 2 vesicular glutamate transporter (VGluT2) are active during theta oscillation and locomotor activity. Optogenetic activation of these neurons at theta frequencies (4-12 Hz) entrains hippocampal theta oscillation and sustains locomotion outlasting the stimulus duration. However, the specific cellular and circuit mechanisms responsible for initiating and sustaining MS VGluT2-driven persistent locomotion and associated hippocampal theta oscillations remain unclear. To address these questions, we optogenetically targeted glutamatergic neurons and monitored MS circuit activity using Neuropixels probes, while simultaneously recording hippocampal local field potential. We compared circuit activity recorded during optically evoked versus voluntary running epochs, and analyzed the network characteristics underlying successful run initiations. By applying cellular classification approaches, we uncovered the detailed contribution of the recorded optically tagged VGluT2 neurons and non-optotagged, putative GABAergic and cholinergic identified MS cell types to locomotion onset and maintenance. We discovered persistent active MS neurons which activity lasted seconds beyond stimulation offset and correlated with locomotion and theta durations. To further test the influence of the network on persistent firing of MS neurons, we used MS slice preparation with a multi-electrode array system and elicited persistent firing in vitro. Notably, this phenomenon was modulated, but not diminished by the application of synaptic blockers. Altogether, our results indicate that the intrinsic excitability of MS VGluT2 neurons drives persistent activity, which, in turn, contributes to the maintenance of prolonged locomotion and indirectly drives hippocampal theta rhythm.