A medullary centre for lapping in mice

Abstract

It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mice. These neuronal groups, IRtPhox2b and Peri5Atoh1, are marked by expression of the pan-autonomic homeobox gene Phox2b and are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve. They are premotor to all jaw-opening and tongue muscles. Stimulation of either, in awake animals, opens the jaw, while IRtPhox2b alone also protracts the tongue. Moreover, stationary stimulation of IRtPhox2b entrains a rhythmic alternation of tongue protraction and retraction, synchronized with jaw opening and closing, that mimics lapping. Finally, fiber photometric recordings show that IRtPhox2b is active during volitional lapping. Our study identifies one of the subcortical nuclei underpinning a stereotyped feeding behavior.

Molecular ontology of the parabrachial nucleus

“…It is not yet clear whether the functional role of Phox2b ‐expressing KF neurons diverges from that of Phox2b ‐expressing supratrigeminal neurons or the contiguous “dA3” population of Phox2b ‐expressing interneurons in the hindbrain reticular formation (Gray, 2013; Hernandez‐Miranda et al., 2017; Kang et al., 2007). Many supratrigeminal neurons send output to cranial motor neurons that pattern movements like chewing, licking, and swallowing (Dempsey et al., 2021; Takatoh et al., 2021; Travers & Norgren, 1983), and in mice, the Phox2b distribution overlaps the locations of neurons labeled by viral retrograde tracing from motor neurons that control orofacial movements (Takatoh et al., 2021). In contrast, very few Phox2b ‐expressing neurons project axons to autonomic and respiratory premotor neurons in the ventrolateral medulla in rats (Kang et al., 2007).…”

Prox2+ and Runx3+ neurons regulate esophageal motility

“…To define the synaptic connectivity of Prox2+/Runx3+ vagal neurons to second order sensory neurons in the nucleus of the solitary tract, we labeled their synapses with SynaptophysinGFP using Prox2/Runx3 SypGFP ( Prox2 FlpO ;Phox2b Cre ;R26 FTLG mice (Dempsey et al, 2021); see Figure 2H for a schema of the FTLG allele). This approach revealed many GFP+ synaptic boutons on Phox2b+ neurons in the nucleus of the solitary tract (NTS) (Figure 2H).…”

“…Ai65 (#021875), Ai80 (#025109), VGlut2 Cre (#016963) mice were obtained from the Jackson Laboratory (Daigle et al ., 2018; Madisen et al, 2015; Vong et al, 2011). Phox2b Cre (D’Autreaux et al ., 2011), and R26 FTLG (Dempsey et al ., 2021) mice were provided by Jean-François Brunet (Institut de Biologie de l’ENS, Paris, France). The Tau ds-DTR (Britz et al ., 2015) mice were a kind gift from Martyn Goulding (Salk Institute).…”

“…Phox2b Cre (D'Autreaux et al, 2011), and R26 FTLG (Dempsey et al, 2021) mice were provided by Jean-François Brunet (Institut de Biologie de l'ENS, Paris, France). The Tau ds-DTR (Britz et al, 2015) mice were a kind gift from Martyn Goulding (Salk Institute).…”

Mafa-dependent GABAergic activity promotes mouse neonatal apneas

“…In the peri12, a fraction of them are premotor neurons to the geniohyoid, a muscle whose activity during resting breathing remains controversial 67 , 68 but that activates during inspiratory-resistive breathing and during airway occlusion possibly through active eccentric contraction to regulate the position of the hyoid bone and increase upper airway size and stability 69 . Airway obstruction is unlikely caused by defective contraction of the sole geniohyoid muscle, further tracing experiments are required to check whether the same geniohyoid (through axonal collateralization 70 ) or other Mafa + inhibitory, premotor neurons lie upstream hypoglossal motoneurons innervating the genioglossus muscle, the other main pharyngeal opener muscle (reviewed in Ref. 15 ), that also locate for part in the peri12 area 71 , 72 .…”