The long-range goal of this research is to understand the cellular and molecular mechanisms that mediate the normal performance and adaptive plasticity of the vestibulo-ocular reflex (VOR). The VOR prevents blurred vision during self-motion by producing eye movements that precisely compensate for motion of the head. Neuronal mechanisms of plasticity enable the VOR to perform accurately in the face of development, trauma, and disease. Although the roles of particular classes of neurons to signal transformations and plasticity have been identified, little is understood about how cellular mechanisms contribute to the day-to-day performance and adaptive capabilities of the VOR. The objective of the proposed research is to elucidate how cerebellar activity influences signalling and plasticity in distinct classes of vestibular nucleus neurons. The central hypothesis is that central vestibular and cerebellar synapses onto vestibular nucleus neurons exhibit activity-dependent plasticity. The proposed research will use a brainstem slice preparation to examine the short and long term synaptic dynamics onto cerebellar target neurons, which mediate cerebellar influences on signaling and plasticity in the VOR. Distinct classes of cerebellar target neurons will be identified by their axonal projections and patterns of cerebellar synaptic cell terminals. The influence of vestibular nerve, commissural, and cerebellar synaptic activity will be examined in cerebellar target neurons and in other identified vestibular nucleus neurons. These studies will provide foundations for targeted investigations of the molecular mechanisms that underlie vestibulo-ocular reflex plasticity as well as for pharmacological treatments of cerebellar disorders and of oculomotor disorders that cause nystagmus.

Public Health Relevance

The goal of this project is to identify cellular mechanisms of eye movement performance and plasticity, with a particular focus on cerebellar influence over the vestibulo-ocular reflex, which is critical for stabilizing images on the retina during self-motion. Cellular mechanistic analyses of vestibular and cerebellar control of eye movements are essential for developing therapeutic treatments both for cerebellar disorders including ataxias and neurodegenerative diseases as well as for devastating disorders of eye movements including nystagmus and consequent oscillopsia.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Araj, Houmam H
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Salk Institute for Biological Studies
La Jolla
United States
Zip Code
Nelson, Alexandra B; Faulstich, Michael; Moghadam, Setareh et al. (2017) BK Channels Are Required for Multisensory Plasticity in the Oculomotor System. Neuron 93:211-220
Kodama, Takashi; du Lac, Sascha (2016) Adaptive Acceleration of Visually Evoked Smooth Eye Movements in Mice. J Neurosci 36:6836-49
Ehmsen, Jeffrey T; Liu, Yong; Wang, Yue et al. (2016) The astrocytic transporter SLC7A10 (Asc-1) mediates glycinergic inhibition of spinal cord motor neurons. Sci Rep 6:35592
McElvain, Lauren E; Faulstich, Michael; Jeanne, James M et al. (2015) Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses. Neuron 85:1132-44
Kodama, Takashi; Guerrero, Shiloh; Shin, Minyoung et al. (2012) Neuronal classification and marker gene identification via single-cell expression profiling of brainstem vestibular neurons subserving cerebellar learning. J Neurosci 32:7819-31
Kolkman, Kristine E; McElvain, Lauren E; du Lac, Sascha (2011) Diverse precerebellar neurons share similar intrinsic excitability. J Neurosci 31:16665-74
Shin, Minyoung; Moghadam, Setareh H; Sekirnjak, Chris et al. (2011) Multiple types of cerebellar target neurons and their circuitry in the vestibulo-ocular reflex. J Neurosci 31:10776-86
van Welie, Ingrid; du Lac, Sascha (2011) Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons. J Neurophysiol 105:1651-9
Kolkman, Kristine E; Moghadam, Setareh H; du Lac, Sascha (2011) Intrinsic physiology of identified neurons in the prepositus hypoglossi and medial vestibular nuclei. J Vestib Res 21:33-47
Gittis, Aryn H; Moghadam, Setareh H; du Lac, Sascha (2010) Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents. J Neurophysiol 104:1625-34

Showing the most recent 10 out of 27 publications