Suckling, Feeding, and Swallowing: Behaviors, Circuits, and Targets for Neurodevelopmental Pathology

Abstract

<jats:p> All mammals must suckle and swallow at birth, and subsequently chew and swallow solid foods, for optimal growth and health. These initially innate behaviors depend critically upon coordinated development of the mouth, tongue, pharynx, and larynx as well as the cranial nerves that control these structures. Disrupted suckling, feeding, and swallowing from birth onward—perinatal dysphagia—is often associated with several neurodevelopmental disorders that subsequently alter complex behaviors. Apparently, a broad range of neurodevelopmental pathologic mechanisms also target oropharyngeal and cranial nerve differentiation. These aberrant mechanisms, including altered patterning, progenitor specification, and neurite growth, prefigure dysphagia and may then compromise circuits for additional behavioral capacities. Thus, perinatal dysphagia may be an early indicator of disrupted genetic and developmental programs that compromise neural circuits and yield a broad range of behavioral deficits in neurodevelopmental disorders. </jats:p>

Aberrant early growth of individual trigeminal sensory and motor axons in a series of mouse genetic models of 22q11.2 deletion syndrome

“…Distal md fascicles divide into progressively smaller fascicles as this CN V branch extends ventrolaterally into Ba1B. As shown previously ( 3 , 6 , 8 ) in LgDel +/− embryos ( Fig. 1B1 ) with a deletion of 28 contiguous 22q11.2 gene orthologues parallel to the minimal critical 22q11.2 deletion in humans ( 4 ), RA-regulated gene expression expands into r2–3 ( Fig.…”

“…We previously defined a partially penetrant gross CN V phenotype in LgDel +/− E10.5 embryos that is apparently related to an expansion of RA-dependent gene expression seen in the anterior hindbrain at E9.5 ( 6 , 8 ). To improve the resolution of these previous analyses, we used immunofluorescent anti-βIII-tubulin labeling ( 3 ) as well as confocal microscopy in whole E10.5 embryos to better resolve the organization and trajectories of peripheral CN V axon fascicles. We note that the changes we summarize here for each genotype are also seen, albeit less clearly, in multiple additional samples of chromogenically labeled, conventionally imaged whole embryo preparations ( 3 , 6 , 8 ; Supplementary Material, Fig.…”

“…We showed previously that LgDel +/− pups have many features of dysphagia—S/F/S disruptions—seen in infants and toddlers with 22q11DS ( 5 , 6 ). The anatomical and behavioral changes are accompanied by additional changes in CNgV and craniofacial differentiation ( 3 , 57 ), as well as physiological and cellular changes in cranial motor neurons ( 58 ). We have identified an extremely early divergence in the developmental program that specifies optimal CN V differentiation.…”

“…Second, detecting changes in initial differentiation of individual neurons remain elusive—especially in early to mid-gestation embryos due to their small size and rapid rate of growth. We addressed these challenges by identifying early divergence of axon growth in a key component—the trigeminal nerve of the developing neural circuit for a well-defined innate behavior, suckling, feeding and swallowing ( 3 ) in the genomically accurate LgDel +/− mouse model of DiGeorge/22q11.2 Deletion Syndrome ( 1 , 4 ), which in humans includes a high frequency of clinically significant disruptions of S/F/S from birth onward ( 3 , 5 ).…”

Variations in maternal vitamin A intake modifies phenotypes in a mouse model of 22q11.2 deletion syndrome

“…Feeding and swallowing requires coordination of the oral cavity, pharynx and esophagus to move a liquid or solid bolus toward the stomach (Maynard, Zohn, Moody, & LaMantia, 2020). Coordination of swallowing requires successive recruitment and then subsequent inhibition of sensory and motor branches of cranial nerves that connect more than 25 oral, facial, and pharyngeal muscles with swallowing centers in the hindbrain (Matsuo & Palmer, 2008).…”