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Dr. Colleen Le Prell

Research in the News

Research Program

Facilities

Grants

Publications

Research Program

Our primary area of research to date has focused on central mechanisms that influence the sensitivity of the inner ear. Specifically, we have worked to identify the functional contributions of projections descending from the lateral regions of the auditory brainstem to the inner ear, where they innervate the auditory nerve, and, to a lesser extent, the inner hair cells. Because these lateral olivocochlear (LOC) neurons innervate the ascending projections of the auditory nerve, they are likely to influence spontaneous activity of the auditory neurons, as well as the ascending auditory signal. Indeed, when we measure spontaneous and sound-driven neural activity in animals that lack this descending pathway, we find that auditory nerve activity is decreased. Currently, we are using psychophysical tests to measure LOC lesion-induced changes in the perception of acoustic signals that vary in frequency or intensity. Other studies are focused on identifying the neurotransmitter substances that LOC neurons release at the auditory nerve synapse to modulate auditory function. Dopamine, dynorphin, enkephalin, GABA, acetylcholine, and CGRP, are all LOC transmitters. Our initial focus has been on dynorphin and CGRP. We measure functional changes that occur when we mimic endogenous transmitter release by delivering receptor agonists, block receptor activity by delivering receptor antagonists, or block the release of LOC transmitters by using 'knock-out' mice that lack the capability to produce specific proteins. Dr. Sanford Bledsoe (University of Michigan) has been a key collaborator in the development of this program.

A second major research program which has the potential to yield significant clinical benefit through the prevention of noise-induced hearing loss is also underway. While working with Dr. Josef Miller in his laboratory at the University of Michigan, we demonstrated that pre and post-noise treatment with dietary micronutrients, including beta-carotene, vitamin C, vitamin E, and magnesium, significantly reduced noise-induced hearing loss in guinea pigs exposed to loud sound. New studies in my laboratory have the following major goals: 1) precise characterization of the pathways to cell death in which the above micronutrient therapy does or does not intervene; and 2) identification of novel therapeutic strategies that include agents that intervene at those distinct points in the pathway to cell death in which micronutrient therapy was not effective. Other new studies have the goal of translation of this therapeutic intervention to man, with demonstration of efficacy in human clinical trials. This is an international effort, and includes coordinated efforts at the University of Michigan, University of Florida, Southern Illinois University, Harvard University, the Karolinska Institutet in Sweden, and Universidad de Castilla-La Mancha as well as a commercial partner: OtoMedicine, Inc., a biotechnology company founded in March 2006.

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Facilities

Dr. Le Prell's laboratory is composed of approximately 1100 square feet of laboratory space at the UF; approximately two-thirds of this laboratory space is located within the ENT research facility at Shands hospital and the remainder is in the Communicore, a medical sciences research building.

The Auditory Neuroscience lab within the ENT facility houses a large walk-in double-walled sound-attenuating chamber. This chamber is set-up for aseptic surgical procedures as well as acute manipulation of the inner ear, and is equipped with state of the art equipment for evaluating hair cell or neural response to sound. In addition, there are 4 smaller sound-attenuated chambers for testing rodents trained to release a small response button when they detect sound, or a change some feature of a repeating sound. This lab is also fully equipped for histochemical tissue processing and microscopy (including fluorescent illumination), and it also contains equipment such as scales and balances, pH meters, vortex mixers, a temperature-controlled water bath, and related instruments. One of the topics under active investigation in the lab is chemical modulation of auditory function by the central nervous system pathway via descending efferent pathways that project from lateral regions of the auditory brainstem to the inner ear.

The Auditory Protection lab within the Communicore building houses a new 4-chamber state of the art Hamilton-Kinder system for measuring the acoustic startle reflex in rodents. This new system will provide the basis for the development of a program to understand the factors causing and contributing to tinnitus and to define agents that will prevent and treat tinnitus. The startle reflex can be attenuated by the presence of a brief, quiet sound preceding the startle signal. When background noise is added to the test chamber, the presence of a silent gap in the noise reduces the startle reflex. A subject that is experiencing tinnitus does not readily detect silent gaps as their tinnitus 'fills in the silent period; thus, the silent gap fails to modulate the startle reflex in a subject with tinnitus. Prevention of noise-induced tinnitus is one of the topics under investigation in the lab. Noise exposures occur inside of a large double-walled sound-proof chamber located inside the Auditory Protection Laboratory. The primary research focus for the Auditory Protection lab is micronutrient-mediated prevention of cell death in the inner ear, and the corresponding hearing loss, that is otherwise induced by noise or ototoxic insult.

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Grants

  1. National Institute of Health, National Institute on Deafness and Communication Disorders (NIH-NIDCD) National Research Service Award F32 DC00367, Auditory System Excitotoxic Trauma: Efferent Protection, Colleen G. Le Prell, Principal Investigator. 7/1/1998-6/30/2001: $31,000 annual direct costs.
  2. American Hearing Research Foundation, Efferent Modulation of Auditory Nerve Activity via Calcitonin-Gene-Related-Peptide, Colleen G. Le Prell, Principal Investigator. 1/1/2005-12/31/2005: $18,108 annual direct costs.
  3. National Institute of Health, National Institute on Deafness and Communication Disorders (NIH-NIDCD) R03 DC 007342, Functional Role of CGRP as an Efferent Neurotransmitter, Colleen G. Le Prell, Principal Investigator. 07/01/2005-06/30/2008: $50,000 annual direct costs.
  4. National Organization for Hearing Research, Age-Related Hearing Loss: Regulation by Calcitonin-Gene-Related-Peptide, Colleen G. Le Prell, Principal Investigator. 02/01/2006-1/31/2007: $20,000 annual direct costs (no cost extension to 5/31/07).
  5. National Institute of Health, National Institute on Deafness and Communication Disorders (NIH-NIDCD) R01 DC 008131, Physiological and Behavioral Assessement of Lateral Efferent Function, Colleen G. Le Prell, Co-Investigator. 07/01/2007-06/30/2012: $250,000 annual direct costs.
  6. National Institute of Health, National Institute on Deafness and Communication Disorders (NIH-NIDCD) R01 DC 008423, Micronutrient Intervention to Reduce Noise-Induced Hearing Loss, Colleen G. Le Prell, Co-Investigator. 12/01/2007-11/30/2011: $478,068 annual direct costs
    (pending).

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Publications

  1. Le Prell, C.G. and Moody, D.B. (2000). Factors influencing the salience of temporal cues in the discrimination of Japanese monkey coo calls. Journal of Experimental Psychology: Animal Behavior Processes, 26, 261-273.
  2. Le Prell, C.G., Niemiec, A.J., and Moody, D.B. (2001). Macaque thresholds for detecting increases in intensity: Effects of formant structure. Hearing Research, 162, 29-42.
  3. Le Prell, C.G., Hauser, M., and Moody, D.B. (2002). Discrete or graded variation within rhesus monkey screams? Psychophysical experiments on classification. Animal Behaviour, 63, 47-62.
  4. Le Prell, C.G. and Moody, D.B. (2002). Detection thresholds for intensity increments in a single harmonic of synthetic Japanese monkey coo calls. Journal of Comparative Psychology, 116, 253-262.
  5. Le Prell, C.G., Shore, S.E., Hughes, L.F., and Bledsoe, S.C. Jr. (2003). Disruption of lateral efferent pathways: Functional changes in auditory evoked responses. Journal of the Association for Research in Otolaryngology, 4, 276-290.
  6. Le Prell, C.G., Dolan, D.F., Schacht, J., Miller, J. M., Lomax, M., and Altschuler, R.A. (2003). Pathways for protection from noise-induced hearing loss. Noise & Health, 5, 1-17.
  7. Le Prell, C.G., Yagi, M., Kawamoto, K., Beyer, L. A., Atkin, G., Raphael, Y., Dolan, D. F., Bledsoe, S. C. Jr., and Moody, D. B. (2004). Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions. Journal of the Acoustical Society of America, 116, 1044-1056.
  8. Le Prell, C.G., Halsey, K., Hughes, L. F., Dolan, D. F., and Bledsoe, S.C. Jr. (2005). Disruption of lateral efferent pathways via a dopaminergic neurotoxin depresses auditory nerve activity. Journal of the Association for Research in Otolaryngology, 6, 48-62.
  9. Yamashita, D., Jiang, H.-Y., Le Prell, C. G., Schacht, J., Miller, J. M. (2005). Post-exposure treatment attenuates noise-induced hearing loss. Neuroscience, 134, 633-642.
  10. Le Prell, C.G., Kawamoto, K., Raphael, Y., and Dolan, D.F. (2006). Electromotile hearing: Evidence that intra-cochlear electrically stimulating the intact guinea pig cochlea produces tone-like percepts, Journal of the Acoustical Society of America, 120, 3889-3900.
  11. Le Prell, C.G., Yamashita, D., Minami, S., Yamasoba, T., and Miller, J.M. (2007). Mechanisms of noise-induced hearing loss indicate multiple methods of prevention, Hearing Research, 226, 22-43.
  12. Le Prell, C.G. (2007). A role for the lateral olivocochlear neurons in auditory function. Focus on 'Selective removal of lateral olivocochlear efferents increases vulnerability to acute acoustic injury'. Journal of Neurophysiology 97, 963-965.
  13. Le Prell, C.G., Hughes, L.F., and Miller, J.M. (2007). A combination of dietary antioxidants and magnesium prevents noise-induced hearing loss and sensory cell death. Free Radical Biology & Medicine, 42, 1454-1463.
  14. Miller, J.M., Le Prell, C.G., Prieskorn, D.M., Wys, N. L., and Altschuler, R.A. (2007). Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: Effects of brain-derived neurotrophic factor and fibroblast growth factor. Journal of Neuroscience Research, 85, 1959-1969.

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This page was last updated Aug. 6, 2008.