Vestibular Research in Sadeghi Lab

Our aim is to reach a better understanding of vestibular signaling and its modulation following compensation or adaptation. Vestibular pathways are very plastic and recalibrate their responses under normal conditions as well as following vestibular disorders. However, this compensation/ adaptation is not complete and following lesions, deficits can be observed in response to more challenging stimuli, such as high frequency or velocity movements. The ultimate goal of studies in the lab is to find practical ways for enhancing vestibular compensation or adaptation in humans.  This can be specifically useful for patients (e.g., after therapeutic vestibular neurectomy) or in conditions where unusual adaptation is required (e.g., space travel). We start by dissecting the pathway at the cellular level in order to understand the mechanisms involved in synaptic signal transmission in this system and then apply the knowledge gained by these studies to live animals. With this approach in mind, two sets of studies are conducted in the lab. 

 

Using in vitro patch clamp recordings in mice, we study the properties of synapses between hair cells, afferent fibers, and efferents in vestibular end organs in mice.  We use a whole tissue preparation of the cristae of the horizontal and superior canals and study synapses by using the patch clamp technique. The main goal of these studies is to understand how signal transmission is modulated at this level. We study different types of receptors mediating afferent (e.g., glutamate AMPA/ NMDA receptors) and efferent (e.g., acetylcholine receptors) inputs as well as membrane properties of both hair cells and afferents (e.g., role of different potassium channels). Knock out animal models provide one of the sources for further studying the role of these receptors/ channels in vestibular signal transmission.

 

We use in vivo recording from single nerve fibers or as field potentials (VsEP) in mice to study modulation of the activity of vestibular-nerve afferentsbefore and after systemic or local application of drugs that target specific receptors and channels.  

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Finally, we test the effect of such modifications of the sensory organs on behavioral measures, such as the gaze stabilization reflex or vestibulo-ocular reflex (VOR).