The broad long-term goals of the application are two-fold: to define the neuron classes in the chick medial vestibular nucleus (MVN) which project axons to the oculomotor, trochlear or abducens nucleus, and to place these neuron classes within a topographic map of the MVN. The MVN contains second-order neurons participating in the three-neuron vestibular reflex pathways controlling posture, balance and eye movements. These neurons show a high degree of plasticity in response to changing visual images and in response to injury and disease. From this, MVN neurons have become an important focus for experiments to understand the role of brain plasticity in the recovery of function after injury or disease. Like most vertebrate vestibular nuclei, the MVN contains neurons with different morphologies and functions whose responses are analyzed most often as a collective group. The unique plastic responses of individual MVN neuron classes is overlooked presently in studies of plasticity and recovery of function after injury or disease. The present experiments represent the first step in profiling MVN neuron classes and their topography in the nucleus. This information may provide the foundation for a breakthrough in understanding the roles which MVN neuron classes play in brain plasticity and vestibular compensation in future experiments. Two main hypotheses drive these projects: (1) MVN neurons can be subdivided into distinct neuron classes by relating their morphology, inputs, and outputs, and (2) MVN neuron classes cluster together within specific MVN regions. The morphology of MVN neurons will be characterized and correlated with whole-cell patch-clamp recordings performed at a key developmental age, embryonic day 13 (E13). At E13, chick vestibular nucleus neurons have acquired many definitive features which are retained in young postnatal animals. Studies of synaptic inputs will include spontaneous synaptic activity and responses to vestibular-nerve stimulation. Studies of outputs will include action potential waveform and firing pattern, and tracing the axon pathways to their target nuclei. Six criteria will be used for profiling MVN neuron classes: (1) neuron cell body size and shape; (2) number of primary dendrites, dendritic orientation and branching pattern; (3) axonal pathway and termination in target nuclei; (4) spike waveform and firing pattern; (5) spontaneous synaptic activity; (6) responses to vestibular-nerve stimulation. Finally, structurally and functionally-defined neuron classes will be placed in a three-dimensional map of the chick MVN. As the basic mechanisms involved in vestibular reflex function are better understood, more effective therapies may be devised to treat vestibular disorders resulting from disease, injury and aging. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DC008715-02
Application #
7422412
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Cyr, Janet
Project Start
2007-05-01
Project End
2009-08-31
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$29,863
Indirect Cost
Name
George Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
043990498
City
Washington
State
DC
Country
United States
Zip Code
20052