Whitlon, Donna, PhD
Research Associate Professor
|Areas of Research||
Cell Biology, Hearing Sciences, Mechanisms of Drug Action
|NU Scholar Profile|
Spiral ganglion neurons carry sound information from the hair cells in the cochlea to the cochlear nucleus in the brain stem. Anything that interferes with the survival or health of these bipolar neurons will interfere with the transmission of sound information and will affect hearing. Damage can be primary or secondary, can be caused by trauma, noise, ototoxic drugs and chemicals and can include loss of synapses, loss of nerve fibers, and cell death. Remarkably, the centrally oriented nerve fibers degenerate more slowly than the peripherally oriented fibers, and can maintain a semblance of their organized arrangement in the cochlear nucleus even when the peripheral fiber has lost its connection to the hair cells. This organization in the brain stem, called “tonotopic” is important for the faithful representation of different frequencies of sound, and its maintenance is important for understanding speech. Not only can spiral ganglion neurons carry information from hair cells to the brain, but in the absence of hair cells, they can also carry information encoded by cochlear implants.
Hearing loss is a much bigger problem than most of us want to believe. According to the National Institute for Deafness and Other Communicative Disorders (NIDCD), approximately 17% of American adults report some degree of hearing loss. And it only gets worse with age. By the time we reach age 75 or older, 47% of us will have a hearing loss.
My laboratory is actively engaged in a research program ultimately aimed at developing drugs to maintain survival of spiral ganglion neurons and to stimulate their nerve fiber regrowth. Survival of spiral ganglion neurons is essential for the functions of both hearing aids and cochlear implants. Regrowth of nerve fibers toward hair cells, either surviving or future regenerated cells, will be essential to reconnect sound information through endogenous neurons. And further, it is thought that regrowth of spiral ganglion peripheral nerve fibers toward a cochlear implant would permit the development of implants with better frequency selectivity and lower power consumption. At this time, as far as we know, there are currently no drugs approved anywhere in the world to maintain neuronal survival and stimulate nerve fiber regrowth in the human cochlea.
We have developed a novel pre-screening procedure that will allow us to evaluate thousands of drugs and compounds for their effects on spiral ganglion neuronal survival and neurite length. The procedure uses cultures of dissociated newborn mouse spiral ganglia, immunolabeling, automated imaging and computer assisted neurite length measurements. The goal is to narrow down the very large field of potential compounds to a few of the most promising that we can then advance to intense examination in an animal model of noise induced hearing loss. In addition, promising compounds can give information on the mechanisms of neurite growth. We recently identified a class of compounds that increases neurite length in vitro, without causing neuronal cell death. We now advance several of that class to in vivo study, examining auditory brain stem responses, and visualizing neuronal survival, synapses and neurite growth by several imaging technologies.
Whitlon DS (2011) Introduction: spiral ganglion neurons. Hearing Research 278:1.
Richter CP, Kumar G, Webster E, Banas SK, Whitlon DS (2011) Unbiased counting of neurons in the cochlea of developing gerbils. Hearing Research 278: 43-51.
Lie M, Grover M, Whitlon DS (2010) Accelerated neurite growth from spiral ganglion neurons exposed to the rho kinase inhibitor H-1152. Neuroscience 169: 855-862.
Whitlon DS, Tieu D, Grover M (2010) Purification and transfection of cochlear Schwann cells. Neuroscience 171:23-30.
Whitlon DS, Tieu D, Grover M, Reilly B, Coulson MT (2009) Spontaneous association of glial cells with regrowing neurites in mixed cultures of dissociated spiral ganglia. Neuroscience 161: 227-235
Whitlon DS, Grover M, Tristano J, Williams T, Coulson MT (2007) Culture conditions determine the prevalence of bipolar and monopolar neurons in cultures of dissociated spiral ganglion. Neuroscience 146:833-840.
Whitlon DS, Ketels KV, Coulson MT, Williams T, Grover M, Edpao W, Richter CP (2006). Survival and morphology of auditory neurons in dissociated cultures of newborn mouse spiral ganglion. Neuroscience 138: 653-662.