Hebbian learning is basis of neuronal plasticity and its effect can best be seen in the induced ocular dominance columns in three eyed frogs where retina ganglion cell axons segregate from each other driven by induced and spontaneous activity. We have developed a new model, the three eared frog model, which allows us to induce vestibular dominance column depending on the orientation and thus stimulation of the grafted ear and have further developed our three- eared model to uncouple linear and angular acceleration and observe the effects on the vestibular-ocular reflex (VOR). In addition, we can use the single pair of Mauthner cells to visualize the segregation of afferents from two ears at the level of a single cell.
Aim1 will combine ear transplantations with various colored fluorescent proteins to image segregation of different semicircular canals in the vestibular nucleus and on Mauthner cell dendrites. In addition, we can observe the effects of motor output by monitoring the VOR in animals with tandem aligned and misaligned semicircular canals.
In Aim 2 this novel model will be utilized to dissect the significance of all activity in this process. Specifically, uing the newly developed CRISPER technique we will delete a gene that has been identified as producing an essential protein for the docking of synaptic vesicles. Without such docking neither spontaneous nor induced activity will be propagated through the nervous system. We will test in specific combinations of the frogs whether the lack of activity in the transplanted ear or in the host or both is particularly important to drive the afferent segregation process. Combined, these two aims will establish that activity is an essential factor for inner ear afferent segregation and will establish the three-eared frog model as a new model to understand those plasticity processes at a cellular level, using the only neuron that can be identified in the vertebrate central nervous system, the Mauthner cell, as an example.

Public Health Relevance

In analogy to three-eyed frogs, we have generated three-eared frogs that demonstrate afferent fiber segregation into vestibular dominance columns. Using this model we will expand mechanisms for plasticity developed in the visual field into the vestibular research. Vestibular plasticity is essential to adjust to differences between ears and changes in vestibular sensation over time, including compensations after vestibular defects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
1R03DC015333-01
Application #
9100314
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Platt, Christopher
Project Start
2016-05-01
Project End
2019-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Iowa
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52246
Glover, Joel C; Elliott, Karen L; Erives, Albert et al. (2018) Wilhelm His' lasting insights into hindbrain and cranial ganglia development and evolution. Dev Biol :
Gordy, Clayton; Straka, Hans; Houston, Douglas W et al. (2018) Transplantation of Ears Provides Insights into Inner Ear Afferent Pathfinding Properties. Dev Neurobiol 78:1064-1080
Fritzsch, Bernd; Elliott, Karen L (2017) Gene, cell, and organ multiplication drives inner ear evolution. Dev Biol 431:3-15
Fritzsch, Bernd; Elliott, Karen L; Glover, Joel C (2017) Gaskell revisited: new insights into spinal autonomics necessitate a revised motor neuron nomenclature. Cell Tissue Res 370:195-209
Fritzsch, Bernd; Elliott, Karen L (2017) Evolution and Development of the Inner Ear Efferent System: Transforming a Motor Neuron Population to Connect to the Most Unusual Motor Protein via Ancient Nicotinic Receptors. Front Cell Neurosci 11:114
Zarei, Kasra; Elliott, Karen L; Zarei, Sanam et al. (2017) A method for detailed movement pattern analysis of tadpole startle response. J Exp Anal Behav 108:113-124
Zarei, Sanam; Zarei, Kasra; Fritzsch, Bernd et al. (2017) Sonic hedgehog antagonists reduce size and alter patterning of the frog inner ear. Dev Neurobiol 77:1385-1400
Elliott, Karen L; Kersigo, Jennifer; Pan, Ning et al. (2017) Spiral Ganglion Neuron Projection Development to the Hindbrain in Mice Lacking Peripheral and/or Central Target Differentiation. Front Neural Circuits 11:25