Distinct Organization and Activation of Brainstem Sensory and Motor Neurons Essential for Suckling, Feeding, and Swallowing

Abstract Body : Abstract:
Suckling, feeding, and swallowing (S/F/S) is an innate, uniquely mammalian behavior that must be in place and fully functional at birth, and then give way to a divergent behavior, ingestion, chewing, and swallowing (I/C/S), at weaning. Despite the centrality of these two behaviors for mammalian survival and maturation, surprisingly little is known about the underlying brainstem circuits for S/F/S or whether they change to accommodate the distinct behavioral demands of I/C/S. In typically nursing infants, nociceptive information relayed via trigeminal nerve (CN V) afferents to the spinal trigeminal nucleus (SpV), and mechanosensory information, relayed via CN V to the principal sensory trigeminal nucleus (PrV) detect S/F/S-related stimuli in the perioral region and anterior oropharynx. Additionally, CN VII, X, and XII provide key motor inputs for successful S/F/S in infants and I/C/S in adults. The organization of the adult mouse brainstem is relatively well defined; however, we recognized that there was no reliable, single atlas that records the basic organization and relative positions of sensory and cranial nerve nuclei during the period of S/F/S. We used a combination of mechanosensory, nociceptive, and motor-neuron selective recombination-dependent or transgenic reporters to generate this resource in P7 and adult WT mice. We are currently validating the identity of sensory relay and cranial motor neurons in S/F/S-related brainstem nuclei whose identity is securely confirmed by our reporters using rapid fluorescent tracers to record what may be transient positions and patterns of innervation. We have also used cFOS immunolabeling in the SpV and PrV, identified securely based upon our new P7 brainstem atlas, of nursing WT pups challenged with graded concentrations of mustard oil, a chemical irritant, applied to perioral skin to quantify nociceptive versus mechanosensory activation. We have shown that cFOS can be used as a sensitive assay to map focal, differential activation of brainstem neurons in response to graded stimuli. In parallel, we are quantifying nociceptive and mechanosensory glutamatergic and GABAeric terminals in the SpV and PrV using a combination of reporter mice and immunolabeling. Together, we are defining a specific and potentially transient organization of brainstem cranial sensory inputs, sensory relay, motor neuron nuclei, and patterns of activity that mediate S/F/S during a brief period of post-natal life in the mouse, and potentially all mammals.