Summary of the Vestibular Laboratory's interests
Our major objectives are:
1) To study the cellular determinants of the response dynamics of the
horizontal semicircular canal. We have chosen toadfish as a model system. Our
view is that the semicircular canals of the vestibular system were highly
evolved several hundreds of million years ago when the vertebrates first
appeared. Bode plots that describe the afferent response dynamics are highly
similar across the vertebrate phyla. Variations between species are likely due
to the different lifestyles experienced by these animals rather than to
fundamental differences in labyrinthine mechanisms. We employ a variety of
techniques in our investigations. These include mathematical modelling, patch
clamp study of isolated hair cells, intracellular recording of receptor
potentials from hair cells in-situ, and extra- and intracellular recording of
primary afferents during experiments designed to understand the contributions
of pressure, endolymph flow, and cupular mechanics to canal responses. We have
recently developed a video microscope to monitor hair cell stereociliary
movement during adequate stimulation in intact preparations.
2) To study the neural substratum responsible for motor learning or
plasticity. We use the vestibulo-ocular reflex as a model system. Experiments
are performed in alert behaving, and anesthetized squirrel monkeys. We employ
intracellular and extracellular recording, and make use of neuroanatomical
techniques for marking single neurons. We employ 2 X and/or 0.5 X lenses in
conjunction with rotation in alert animals to either raise or lower the gain
of the reflex. Reflex gain begins to change in about 30 minutes and is 60%
complete in about six hours. We are able to follow the changes in the
responses of single neurons during the learning and correlate these changes
with the learned behavior. We utilize substances such as muscimole to
inactivate parts of the learning circuit to study the effects of this
temporary ablation. We often record "downstream" from the site of inactivation
to see the effects of removing a part of the circuitry on single cells. With
this and other methods, we have been able to dissect components of the signal
flow through the system and are arriving at a theory of learning to account
for the observed behavior. We are presently configuring a mathematical model
of the learning.
3) To study the neural control and generation of ocular gaze. We have a long
term interest in the control and generation of saccadic eye movements. The
superior colliculus encodes impending eye movement in a vectorial reference
frame that moves with the eyes (retinotopic). The extraocular motoneurons and
immediately prenuclear burst neurons encode eye movements in a metric
reference frame. We are interested in how the brain makes the transformation
from vectorial to metric coordinates. We utilize extracellular recording of
neurons in relation to gaze in alert animals to understand this system.
However, our major tool is the intraaxonal injection of neurons in the circuit
with anatomical tracer substances. We first characterize the firing patterns
of neurons, then inject them, and subsequently study their axonal morphology
to determine their connectivity. This leads to an understanding of the neural
circuits involved and will ultimately provide a model of the function of the
system.
4) To determine the operation and action of the efferent vestibular and
auditory systems. Experiments are performed at both the cellular and
behavioral levels in toadfish. We think that the key to understanding the
function and purpose of CNS efferent control is to relate the activation of
the efferent system to the behavior of the animal in natural or quasi-natural
settings. Our recent work suggests that the organism utilizes the efferent
system to tune the octavolateralis periphery to emphasize certain behaviorally
relevant aspects of incoming sensory information. It is not surprising that an
organism can turn its attention to certain important aspects of its sensory
environment, but it seems noteworthy that the brain is employed to tune
peripheral receptors to accomplish this goal. (cf Tricas and Highstein, 1990,
91, and Highstein's review article, 1991).