Persistent Firing Neurons in the Medial Septum Drive Arousal and Locomotion

The medial septum and diagonal band of Broca (MSDB) serve as a central hub in an ascending brainstem pathway that conveys sensory and motor signals to the limbic system. However, the cellular and circuit mechanisms underlying these functions remain unclear. Here, we show that transient optogenetic activation of MSDB VGluT2⁺ neurons initiates a structured arousal sequence -beginning with facial movements, followed by pupil dilation and locomotion. Neuropixels recordings reveal persistent MSDB neuronal activity that strongly correlates with arousal-related behaviors. We demonstrate that persistent firing (PF) is an intrinsic property of a subset of MSDB neurons, independent of ongoing synaptic input. PF neurons, along with putative GABAergic theta-bursting neurons activity, reliably predicted behavioral initiation. These findings suggest that PF neurons orchestrate the transition from preparatory movements to full behavioral engagement, thus bridging sensory input with locomotor arousal and supporting state transitions in the limbic system.