Yakusheva Lab

Overview

Health problems associated with motor control and balance are the most common neurological disorders affecting the world population today. Our research is aimed to understanding motor control and balance in the normal and diseased brain, with the ultimate goal of paving the way towards finding cures and therapies for rehabilitation.

The goal of our research is to study the role of the vestibulo-cerebellum in motor control, balance and spatial navigation. The vestibulo-cerebellum is a region of the cerebellar cortex that comprises the floccular lobe and the posterior vermis. Currently, our lab is testing the hypothesis that the floccular lobe computes a forward model (predictive model) of the eye movement from vestibular and efferent copy information, and that the posterior vermis computes an estimate of our heading (translation) and orientation in space from semicircular canals and otolith information. Our experimental techniques include single unit recordings, pharmacology, behavioral neuroscience, mouse neurogenetics, histochemistry and computational modeling.

Research Projects

A leading hypothesis on cerebellar cortex function states that the cerebellar cortex generates predictions of the consequences of our movement (also called forward models) that are used for fine motor control and balance. We are currently testing this hypothesis in the two lobes that comprise the vestibulo-cerebellum: The floccular lobe and the posterior vermis (Nodulus and ventral Uvula). Our experimental techniques include single unit recordings, pharmacology, behavioral neuroscience, mouse neurogenetics, histochemistry and computational modeling.

The flocculus lobe

The most characteristic clinical manifestation of damage in the floccular lobe is the presence of downbeat nystagmus and the inability, or difficulty, in adapting the gain of the vestibulo-ocular reflex (e.g. during Meniere’s disease). We and others have shown that the floccular lobe combines vestibular and efferent copy information to generate appropriate commands that stabilize gaze during movements of the head and movements the object of interest. We have also shown that lesions in the floccular lode prevent the central nervous system from learning new associations between head movements and compensatory eye movements. Thus, the floccular node is necessary for normal pursuit behavior and to control the output of the vestibulo-ocular reflex (VOR). Our lab’s current research focuses on testing the hypothesis that the cerebellar flocculus computes an adaptable forward model of the eye movement from vestibular and efferent copy information. We are very interested in the role that cerebellar cortex interneurons play in these computations.

The posterior vermis

The posterior vermis plays an essential role in balance control and spatial navigation. Our general hypothesis is that this structure uses information from the vestibular organs (semicircular canals and otoliths) to generate an estimate of our heading (translation) and orientation (tilt and roll) in space. We have previously published data supporting this view. We studied the information carried by input elements (mossy and climbing fibers) and by output elements (Purkinje cells) to the structure. Currently, we are using a mechanistic approach to study posterior vermis function. We are investigating the specific computations carried out by local circuit neurons in the posterior vermis as well as specific synapses.