2009 Research Grants Awarded
- Lawrence Lustig, MD, “The role of synucleins in the mammalian cochlea”
University of California at San Francisco
- Takako Kondo, Ph.D., “A novel stem cell replacement therapy for damaged spiral ganglion neurons”
Indiana University School of Medicine, Indianapolis
- Donna Whitlon, Ph.D., “Schwann cells in normal and noise damaged cochleas”
Northwestern University, Chicago
- Lisa Potts, Ph.D., “Speech evoked auditory brainstem responses in normal-hearing and hearing impaired adults with and without amplification”
Washington University, St. Louis, MO
- Matthew Banks, Ph.D., “Neural basis for sensory discrimination and perceptual learning in auditory cortex”
University of Wisconsin, Madison
Lawrence Lustig, MD, “The role of synucleins in the mammalian cochlea”
It is known that poor auditory nerve functionality within the cochlea can play a significant role in hearing loss, as can the death of hair cells—the hair-like cells in the cochlea that vibrate in response to sound. Neurons in the cochlea transmit the vibrations of hair cells as nervous impulses to the auditory nerve which carries the signal to the brain where it is interpreted as sound.
Lustig’s group has been studying a group of proteins called synucleins, which are believed to play a part in the transmission of nerve impulses between neurons, or in the synapse. There are three synucleins that seem to be involved in synaptic nerve signal transmission within the cochlea. It is known that changes in synuclein functioning negatively impact hearing by causing age-related hearing loss and hair cell death. Lustig and colleagues are interested in finding out exactly if and how synucleins are involved in hearing loss within the cochlea. Because synucleins have also been implicated in Parkinson’s Disease and other neurodegenerative diseases, understanding them is very important.
Takako Kondo, Ph.D., “A novel stem cell replacement therapy for damaged spiral ganglion neurons”
Spiral ganglion nerves (the nerves that carry signals generated by the hair cells in the cochlea), when damaged, lead to hearing loss. They do not significantly regenerate after they have degraded, and this is a major focus of hearing loss researchers.
Stem cells have been considered as a possible therapy to restore lost or damaged spiral ganglion neurons, but no studies to date have been successful at accomplishing this. A substance called T1x3 promotes the development of embryonic stem cells (ES cells) into neurons that can generate action potentials. This suggests that T1x3-expressing ES cells may be useful in replacing spiral ganglion neurons that have been lost or damaged in the inner ear. But, little is known about how these ES cell-derived neurons may develop and work. Kondo and colleagues will focus on identifying molecules in the microenvironment of implanted T1x3-expressing ES cells in the cochlea to see if any of them may promote neural growth and guide the direction of axonal growth. Kondo will also test whether ES cells treated with T1x3 grow in animal cochleas and if they will make synaptic connections with hair cells.
Donna Whitlon, Ph.D., “Schwann cells in normal and noise damaged cochleas”
Schwann cells are auxiliary cells that are found wrapped around nerve fibers and provide insulation through the production of a substance called myelin. They also promote survival, growth and regeneration of nerve fibers. Precursor and immature Schwann cells are especially helpful in helping in nerve regeneration because they retain the ability to express growth factors that can stimulate nerve growth. Mature Schwann cells do not have this ability.
There are few studies of the effect of Schwann cells on neurite growth and differentiation in the cochlea. Whitlon and colleagues have developed a cell culture that contains mouse spiral ganglion cells and other cell types. They noticed that in studies involving the regeneration of nerve fibers in their culture, the growing neuritis associated strongly with Schwann cells. The neuritis even changed their regularly straight growth patterns to bend towards Schwann cells. Whitlon’s group will study how Schwann cells encourage the survival and directional growth of damaged spiral ganglion nerve fibers. They will also look at how Schwann cells respond to noise-induced cochlear trauma.
Lisa Potts, Ph.D., “Speech evoked auditory brainstem responses in normal-hearing and hearing impaired adults with and without amplification”
Auditory brainstem responses evoked with speech stimuli (the neural response of the brainstem to speech) provide information on how speech is encoded by the auditory system. Some children with learning problems have abnormal brainstem responses to speech. Very little is known about the neural encoding of speech in people with hearing loss and how amplification of sound may change encoding to improve (or not) speech perception.
Potts and colleagues will record brainstem responses to normal and amplified sound in people with and without hearing loss. Her team hopes to increase understanding of neural encoding at the brainstem in the presence of hearing loss, which could have widespread effects for optimizing hearing aid and cochlear implant fittings in both children and adults.
Matthew Banks, Ph.D., “Neural basis for sensory discrimination and perceptual learning in auditory cortex”
Banks and colleagues will explore the neural basis for sensory discrimination and perceptual learning in the auditory cortex by recording cortical neural activity from rats while the animals perform an auditory discrimination task. Analysis of the neural responses recorded during single trials will provide insight into how cortical circuits process real-time information used for identifying acoustic stimuli. Monitoring changes ion neural responses as animals learn the task and hone their skills at discriminating between more difficult stimulus pairs will clarify how these circuits change and self-organize to optimize the information-gathering process for distinguishing sensory stimuli.