Behavioral Learning

In our lab we are trying to understand the neural basis of behavior. A fundamental part in this quest is, of course, measuring the actual behavior. In our system that means recording eye movements.

We use an infrared video eye-tracking system to acquire an image of the mouse’s eye. The mouse is restrained but awake in a small tube that is positioned in the center of our stimulation setup (see picture). A miniature video camera is aimed at the mouse’s eye and the image is fed into a computer which tracks motion of the pupil. We provide visual stimuli by rotating the striped drum around the animal and vestibular stimuli by rotating the entire platform. The sample video shows eye movements of a mouse in response to sinusoidal turntable rotations in the light at 0.7 Hz and ± 5 degrees amplitude. Learning in this system is expressed as changes in the eye movements evoked by visual or vestibular stimulation. We test hypotheses about the role of particular cellular mechanisms in learning and memory storage by examining behavior in transgenic mice.

Sample Eye Movement Video
Sample Eye Movement Trace

Slice Physiology

In addition to our behavioral studies in mice, we study neuronal networks involved in the VOR in an in vitro slice preparation. Crucial for the proper function of the VOR are the brainstem vestibular nuclei located in the brainstem. We therefore target vestibular nucleus neurons for electrophysiological recordings with variations of the patch-clamp technique. Whole-cell current clamp recordings are made to characterize the firing patterns of vestibular neurons, while whole-cell and cell-attached patch clamp are used to study voltage-gated ion channels expressed in these neurons. We are particularly interested in how experience modifies both intrinsic firing properties and synaptic transmission. To this end we are exploring new mechanisms of plasticity that may be unique to spontaneously firing neurons. In addition, we examine cellular properties of VOR neurons in brain slices obtained from mice prior to and after different forms of learning.

Use of Biological Fluorophores

The VOR circuit comprises many types of neurons that perform different roles in eye movement behavior and learning. We are developing transgenic mice to identify critical neuronal subpopulations and target them for electrophysiological recordings and biochemical analyses. One such mouse expresses GFP in Purkinje cells of the cerebellum, including their axons and terminals. This L7-tau-GFP mouse (Sekirnjak et al 2003) enables us to identify neurons in the vestibular nucleus that are innervated by Purkinje cells and to study their contribution to behavioral learning.

Dissociated Cell Project

The acutely dissociated cell preparation allows us to isolate specific currents in MVN neurons. We would like to understand how these currents give rise to spontaneous activity and how their properties and expression are changed by experience.

Molecular Biology

Firing rate potentiation is a novel form of plasticity in which synaptic inhibition triggers persistent increases in intrinsic neuronal excitability in spontaneously firing vestibular nucleus neurons (Nelson et al 2003). The mechanism of firing rate potentiation involves decreases in CaMKII activity and reductions in Ca2+-activated K+ currents carried through BK channels. We would like to understand the nature of the interaction between these two molecules and how they are regulated by experience.