Tongue maturation deficits in a mouse model of Down syndrome

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PROJECT SUMMARY / ABSTRACT Atypical and delayed oromotor development is a well-known clinical aspect of Down syndrome (DS) and contributes to devastating challenges in speech, feeding, and swallowing. These challenges can affect the majority of individuals with DS, with profound consequences for quality of life and health. The tongue and brainstem are both complex systems that undergo rapid changes during early postnatal development and are critical for speech and swallowing. However, the central and peripheral changes occurring in early childhood that permit postnatal expansion in movement and function of the tongue are poorly understood in typical development and in DS. Because early childhood is a time of rapid development during which the neuromuscular system is plastic, altered tongue activity during this time may also alter the postnatal maturation of the tongue neuromuscular system. However, the impact of altered lingual activity on intrinsic tongue and brainstem maturation in early post-natal development has rarely been studied and is therefore unknown. We hypothesize that DS is associated with developmental delays in maturation of the tongue neuromuscular system. The proposed work is highly significant in using mouse models to advance understanding of a developmental disorder in which atypical tongue function contributes to compromise of speech intelligibility and health. Aim 1 will generate normative data for the study of tongue and brainstem maturation with reference to three consecutive early postnatal ages and will determine how DS impacts lingual development. This will be achieved through behavioral, immunofluorescence, and gene expression studies of tongue muscles and brainstem in the Ts65Dn mouse model of DS in comparison to typical sibling controls. Aim 2 will determine whether lingual activity levels after weaning impact maturation of the tongue neuromuscular system. This aim will be achieved through analysis of tongue and brainstem before weaning and after 2 weeks of an ecologically valid post-weaning condition in which all mice naturally refrain from licking due to a liquid consistency modification. This aim will clarify the extent to which shifts in tongue activity imposed by environmental modifications elicit changes in postnatal maturation of the tongue and brainstem in Ts65Dn mice and in typical sibling controls. Collectively, these aims will further the science underlying both typical and delayed lingual maturation. This work will also shed light on basic biological implications of feeding interventions used with children with DS that alter oromotor activity. As such, this work will provide basic knowledge for future efforts to develop biologically based approaches for successful resolution of pediatric oromotor disorders. These goals will establish an experimental framework to advance biologically informed treatments for developmental speech, feeding, and swallowing disorders.