Developmental mechanisms in the formation and function of sensory-motor circuits responsible for suckling and mastication.

Project summary The sensory-motor circuits are specialized neuronal networks that modulate movement. During development, the proper circuit assembly is fundamental in performing coordinated muscle contraction. During early postnatal development, mammals are heavily dependent on the intake of food. To achieve this, they rely on the suckling

ability which transitions into mastication behavior, led by orofacial muscle activity. However, the mechanism of formation, maturation, and transition from suckling to mastication behaviors, fundamental to surviving adulthood, are poorly understood. Importantly, dysfunction in these behaviors may lead to neurodegenerative disease. The

masseter muscle is the main jaw-closing muscle and is the main muscle implicated in maintaining the correct nutrient intake. The mesencephalic trigeminal nucleus (MesV) is a group of primary sensory neurons within the brainstem that innervates the masseter muscle, projecting to the corresponding motor neuron pool. Additionally,

a population of periodontal pressoreceptor somas is also located in the MesV. This particular characteristic could be related to the modulation of the masseter muscle activity by periodontal pressoreceptors activation. I hypothesize that the sensory-motor circuits controlling the masseter muscles during normal development are

modified in an age-dependent manner to transition from suckling to masticatory behavior and that periodontal pressoreceptors participate in muscle activity modulation. This project aims to explore the mechanisms of assembly and modulation of sensory-motor circuits during healthy development of the masseter muscle, and

how dysfunction in these two behaviors impacts the neurodevelopmental neurodegenerative disease, spinal muscular atrophy (SMA). Unraveling the developmental mechanisms of sensory-motor circuit assembly and function is fundamental to our understanding of the mechanisms causing the disease. Using genetic mouse

models, and retrograde tracing, I will map the orofacial sensory-motor circuit formation and maturation in normal development. State of art behavioral assays and electrophysiological pair-recordings, will provide the characterization of sensory-motor circuit activation in an aged-dependent manner. SMA is caused by the deletion

of the Survival Motor Neuron 1 gene, resulting in a deficiency of the SMN protein. SMA is the most important cause of death in infants, and its hallmarks are selective motor neuron death, muscle atrophy, and impairment of muscle movements. In SMA disease, clinical evidence as well as work from animal models show that the

nutrient intake is severely affected. I hypothesize that the masseter sensory-motor circuit is impaired in SMA, resulting in dysfunctional suckling and masticatory behaviors. To understand these mechanisms, I will use a well-established SMA animal model (SMNΔ7 mice), together with immunohistochemistry, and behavioral assays.

In sum, this project will provide important insights into the development and function of orofacial behaviors both during healthy development and under neurodegenerative conditions.