- ASSOCIATE PROFESSOR Neurology, Vesticular/Ocular
- ASSOCIATE PROFESSOR Neuroscience
ResearchSpecific Clinical/Research Interest: Neuronanatomical studies of functionally-defined central and peripheral vestibular system structures
Current Students: College intern: Melissa Magrath
Research Personnel: Drs. Giorgio Martinelli and Victor L. Friedrich Jr.; Research Associate: Dr. Ewa Kukielka
Summary of Research Studies:
Our laboratory utilizes contemporary neuroanatomical approaches to identify the neurobiological bases for disorders of balance, equilibrium and movement. Light, electron, and confocal microscopy are utilized in conjunction with neuronal reconstructions, tract-tracing, immunocytochemistry, fluorescence histochemistry, hybridoma production and neurophysiological studies. Our main projects are summarized below:
(1) Studies of rat and mouse vestibular nuclei seek to identify the morphology, cell biology, synaptology, neurotransmitter, and receptor attributes of neurons involved in functional pathways of the vestibulo-ocular, vestibulo-spinal and vestibulo-autonomic reflexes. We have demonstrated the roles of GABA and the GABAB receptor in neurons related to the velocity storage pathway, as well as the presence of GABAergic vestibular cells that are not involved in this mechanism and which we speculate are classic interneurons. We are currently examining the neurotransmitter phenotype and receptor distributions in neurons involved in vestibulo-spinal and vestibulo-autonomic pathways and functions.
(2) Studies conducted with NASA are being conducted to identify and characterize the morphologic alterations in rat cerebellar Purkinje cells that occur during exposure to altered gravitational environments. We are examining the ultrastructure of the vestibular cerebellum obtained from rats flown on a space shuttle mission, as well as rats exposed to hypergravity stimulation through centrifugation. Results thus far indicate that there are marked qualitative alterations in the neuronal cytoskeleton, synaptology, and ultrastructural organization of the nodulus of rats transiently exposed to micro- and hyper-gravity. The underlying cell biology of these alterations is curently being investigated.
(3) Experiments are being performed to identify the vestibular neurons and circuits that utilize nitric oxide for intercellular signaling, and the relationship between nitric oxide-producing neurons, and GABAergic and glutamatergic vestibular pathways. Our results suggest that several different morphologic types of vestibular neurons utilize nitric oxide. These cells have different ultrastructural features, and have different distributions throughout the individual vestibular nuclei, suggesting that nitric oxide participates in several different functional pathways of the vestibular system.
(4) Studies of the peripheral vestibular system are identifying the ultrastructural organization of functionally characterized circuits in the crista ampullares of the horizontal semicircular canal of the toadfish and the posterior canal of the turtle. This work involves collaboration with investigators at the Marine Biological Laboratories at Woods Hole. Physiologically characterized primary afferent fibers and sensory hair cells are reconstructed and analyzed by multiphoton and electron microscopy. We are pursing the overall hypothesis that differences in hair cell phenotype and postsynaptic receptor populations shape the neural code conveyed to the brain by different classes of primary afferent fibers.
Friedrich VL Jr, Martinelli GR, Prell GD, Holstein GR. Distribution and cellular localization of imidazoleacetic acid-ribotide, an endogenous ligand at imidazol(in)e and adrenergic receptors, in rat brain. J. Chem. Neuroanat 2007; 33(1): 53-64.
Martinelli GR, Friedrich VL Jr, Prell GD, Holstein GR. Vestibular neurons in the rat contain Imidazoleacetic acid-ribotide, a putative neurotransmitter involved in blood pressure regulation. J. comp. Neurol 2007; 501(4): 568-581.
Holstein GR, Rabbitt RD, Martinelli GP, Frederich VL Jr, Boyle RD, Highstein SM. Convergence of excitatory and inhibitory hair cell transmitters shapes vestibular afferent responses. Proc Natl Acad Sci USA 2004 Nov 2; 101(44): 15766-71.
Prell GD, Martinelli GP, Holstein GR, Matulic-Adamic J, Watanabe KA, Chan SL, Morgan NG, Haxhiu MA, Ernsberger P. Imidazoleacetic acid-ribotide: an endogenous ligand that stimulates imidazol(in)e receptors. Proc Natl Acad Sci USA 2004 Sep 14; 101(37): 13677-82.
Martinelli GP, Friedrich VL Jr, Holstein GR. Monoclonal L-citrulline immunostaining identifies nitric oxide production sites within neurons. Neuroscience 2002; 114(1): 111-22.
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Dr. Holstein did not report having any of the following types of financial relationships with industry during 2014 and/or 2015: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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