Dual role of the mesencephalic locomotor region in modulating visually evoked escape response

Locomotion initiation and speed control are dependent on activity in the Mesencephalic Locomotor Region (MLR). In mammals the MLR is constituted of glutamatergic neurons in the pedunculopontine nucleus (PPN) and cuneiform nucleus (CnF) that act together to control locomotion speed. To further understand their contribution in the context of sensory evoked locomotor behaviour, we asked how visually evoked locomotor escape responses in mice are modulated by MLR. To evoke natural escape we used innate looming responses. Using chemogenetic inhibition of targeted Vglut2+ glutamatergic neurons in PPN or CnF, our results show a weakened looming response when either CnF or PPN was inhibited. Specifically, inhibition of Vglut2+ CnF neurons reduced the probability of evoking escape locomotion and reduced the speed of locomotion when evoked, while inhibition of Vglut2+ PPN neurons primarily reduced the speed of the evoked escape locomotion with no effect on the probability of evoking the response. Further, escapes similar to visually evoked responses were also evoked by optogenetic activation of retrogradely labelled Vglut2+ superior collicular projections to CnF in the presence. Together, these results point towards a dual role of MLR with Vglut2+ CnF neurons important for setting the threshold for evoking the visually evoked response while PPN and CnF are corporate to determine the speed of the escape locomotion when executed. Our data support previous anatomical connections between the superior colliculus and PPN and CnF glutamatergic neurons.This work was supported by:Novo Nordisk Laureate Program (NNF15OC0014186) and the Lundbeck Foundation (R345-2020-1769).