Supratrigeminal bilaterally projecting neurons maintain basal tone and enable bilateral phasic activation of jaw-closing muscles

Abstract

Anatomical studies have identified brainstem neurons that project bilaterally to left and right oromotor pools, which could potentially mediate bilateral muscle coordination. We use retrograde lentiviruses combined with a split-intein-mediated split-Cre-recombinase system in mice to isolate, characterize, and manipulate a population of neurons projecting to both the left and right jaw-closing trigeminal motoneurons.Wefind that these bilaterally projecting premotor neurons (BPNs) reside primarily in the supratrigeminal nucleus (SupV) and the parvicellular and intermediate reticular regions dorsal to the facial motor nucleus. These BPNs also project to multiple midbrain and brainstem targets implicated in orofacial sensorimotor control, and consist of a mix of glutamatergic, GABAergic, and glycinergic neurons, which can drive both excitatory and inhibitory inputs to trigeminal motoneurons when optogenetically activated in slice. Silencing BPNs with tetanus toxin light chain (TeNT) increases bilateral masseter activation during chewing, an effect driven by the expression ofTeNTinSupVBPNs. Acute unilateral optogenetic inhibition ofSupVBPNsidentifies a group of tonically active neurons that function to lower masseter muscle tone, whereas unilateral optogenetic activation of SupV BPNs is sufficient to induce bilateral masseter activation both during resting state and during chewing. These results provide evidence for SupV BPNs in tonically modulating jawclosing muscle tone and in mediating bilateral jaw closing.