The impact of autism risk genes on oromotor activities

A common feature in autism spectrum disorder (ASD) is difficulty with speech, absent speech, and/or poor oral motor control. The challenge to produce these seemingly simple behaviors leads to behavioral outbursts of frustration from an inability to communicate and unbalanced nutrition resulting from anxiety associated with eating. These challenges are faced daily and impact mental and physical health of the autistic individual and those providing care. The ineffective execution of these behaviors is typically explained as an inability to learn or socially interact, but this explanation falls short when attempting to account for the innate and subconscious nature in which they are produced by the brainstem. Put another way, we can produce sounds and swallows without learning from others’ cues. Here, the investigators will extend upon earlier research to continue characterizing if changes in the innate brainstem oral-upper airway breathing motor patterning systems are incorrectly hardwired in many autism mouse models for ‘Category 1’ genes. This project builds upon the investigators’ pilot work by extending basic characterization of phonation and swallowing into multiple mouse models for ASD. Innate oro-upper airway motor actions, like phonation and swallowing, are produced by collections of neurons in the brainstem, called ‘central pattern generators’ (CPGs). Since these behaviors use overlapping groups of muscles, like how the larynx is used for both sound production during speech and airway protection during swallows, the brainstem CPGs that encode them also co-mingle. Here, the presumption is that individuals with autism that have oromotor / speech challenges have dysfunction in these overlapping CPGs, and testing this model is the central goal of this project. Recently the investigators identified a novel CPG for neonatal mouse cry vocalizations, and were able to characterize its role in producing the intricate intonation pitch patterns during adult mouse vocalizations and the activities of the underlying breathing and laryngeal muscles that encode them. Additionally, during this time, the researchers established a novel behavioral paradigm to characterize the coordination of the tongue, larynx, and breath that is needed to correctly swallow. Now, they plan to use these two behaviors and measurable muscle motor patterns as a platform to determine if ASD mouse models have generalized oromotor dyscoordination and to establish if the dysfunction originates from atypical brainstem CPGs. This work is relevant to understanding the impact of gene mutations that are causally linked to ASD on the physiology of the brain and body. This project seeks to understand how multiple different genes converge upon the function of the brainstem oromotor pattern generators to alter behaviors like phonation and swallowing. This work has the potential to provide mechanistic insights into some of the most common behavioral features in ASD that, as of now, are solely treated with speech therapy.