Structure and function of the efferent vestibular system

The Efferent Vestibular System (EVS) has been an important topic of vestibular research since its description more than 60 years ago. Surprisingly and unlike its auditory counterpart (the olivocochlear efferent system), the exact function of EVS in balance behaviour is still not fully understood. To date, descriptions of the detailed morphology of the EVS in one of the most widely used laboratory model organisms, the mouse have been lacking. Indirect electrophysiological experiments have shown that EVS has a varied and remarkably complex effect on the vestibular sensory neuroepithelium, both excitation and inhibition, depending on the contact site and receptor subtype. In recent years, the synaptic mechanisms at the afferent-efferent synapse have been the focus of research investigating the EVS, and some valuable studies have described the key receptors and proposed signal transduc2on pathways of the ves2bular efferent synapse. However, an important piece of the puzzle is still missing – it is still not known when Efferent Vestibular Nucleus (EVN or ‘group e’) neurons are active. In other words, what would be an adequate stimulus and what conditions are required to generate EVN activity. It has been technically challenging to record EVN activity in vivo, given the small size of the nucleus, its relatively low cell count, and its deep brainstem location. In fact, only two studies were able to record from EVN neurons in demobilized, spinalized animals, and never during freely moving behaviour. The main goal of my PhD research project was to advance our current understanding of the EVS. First, I mapped the detailed anatomy of the central and peripheral EVS in the mouse, which served as a foundation for the electrophysiological and optical experiments. Second, to characterize EVN neuronal activity in vivo during various behavioural conditions, including the induction of motion sickness, to better understand when these neurons are activated or suppressed. In doing so, I present the first in vivo calcium imaging recordings of EVN neurons using brain-implanted miniaturized microscopes.