Studying the Function of Long-Range Projecting VIP-Expressing Neurons in the Facial Motor Nucleus

Abstract

The vestibular system is critical for regulating balance and postural maintenance in many vertebrates. The medial vestibular nuclei (MVN) in the brainstem are known to serve as a hub for receiving and relaying sensory information that is important for vestibular function. While considerable research has been dedicated to understanding how MVN regulate gaze stabilization and spatial orientation/perception, little is known about its connections with other brainstem nuclei that play critical roles for fine-tuning posture and balance. In this thesis, we identified a population of vasoactive intestinal peptide (VIP)-expressing neurons in the facial motor nucleus (FMN) of the brainstem that provide long-range inputs to MVN. Lower motoneurons in FMN have been shown to mediate specific orofacial and vibrissal muscle movements, but these FMN^VIP neurons have never been described. We employed advanced viral tracing methods, in vivo fiber photometry, and cell-type specific ablation and chemogenetic manipulations to study whether and how FMN^VIP neurons contribute to vestibular-mediated balance maintenance. Ablation or acute silencing of FMN^VIP neurons altered the animals' balance performance without affecting their gaze stabilization. Intriguingly, we found that these FMN^VIP neurons are cholinergic, rather than glutamatergic or GABAergic, and using anterograde monosynaptic labeling, we further identified that the major postsynaptic targets of FMN^VIP neurons are the GABAergic neurons in MVN. In vivo Ca²⁺ imaging of FMN^VIP neurons and ACh sensor recordings in MVN demonstrated that FMN^VIP neurons are activated only when the animal's balance is challenged, and they release ACh to modulate MVN neuronal activity and fine-tune body posture for balance maintenance. Lastly, cell-type specific rabies tracing revealed that the major input regions to FMN^VIP neurons arise from the reticular formation, a phylogenetically old brain structure that is known to regulate balance. Altogether, the work from this thesis unveils a new brainstem circuit pathway that bridge the reticular with vestibular nuclei to regulate balance and postural maintenance.