Neural Circuits Controlling Lacrimation

PROJECT SUMMARY Tear secretion (lacrimation) is an essential mechanism that lubricates our eyes and helps reduce eye irritants and microbial infections. Lacrimal deficiency is associated with many systemic or ocular diseases including primary Sjögren's syndrome, lupus, dry eyes, congenital alacrima, and viral infections. Previous studies have suggested that the superior salivatory nucleus (SSN) controls lacrimation. However, direct molecular and genetic evidence is lacking. We recently identified a highly restricted neuronal population in mouse SSN. Ablation of this neuronal population remarkably reduces lacrimation in mice, suggesting that this neuronal population controls lacrimation. To test this hypothesis, we will first determine the efferent targets and physiological properties of these SSN neurons (Aim 1). Results from these experiments will provide valuable information regarding the encoding and transmission of lacrimal signals. Second, we will investigate the role of these SSN neurons in controlling lacrimation by specific ablation or activation of this neuronal population (Aim 2). Results from these experiments will provide functional evidence for SSN control of lacrimation. Finally, we will test these SSN neurons receive sensory inputs from ocular surface and mediate reflex lacrimation (Aim 3). Results from these experiments will help define previously unrecognized connections between ocular sensory inputs and SSN, offering novel insights into the neural mechanism underlying the reflex lacrimation. In summary, our proposed research will help reveal the neural circuit for lacrimation and provide foundational knowledge for future studies of lacrimation deficiency associated with ocular or systemic diseases.