Anna Dondzillo, PhD
Anna Dondzillo, PhD is a neuroscientist interested in signal processing in the aging auditory system. Specifically, how different cell types and network connectivity define neuronal processing. Dr. Dondzillo’s expertise in auditory brainstem synaptic and neuronal network anatomy as well as synaptic physiology developed during her doctoral training in the Max Planck Institute in Heidelberg, and the postdoctoral training at the Universities of Heidelberg and Colorado. Her studies of auditory brainstem in rodent, using stereotaxic brain injections, and single cell recordings have shown involvement of inhibitory circuits in the synaptic processing of neurons in a major auditory brainstem nucleus, known as MNTB. The MNTB, itself consisting of inhibitory neurons, is important in sound source localization. Using single cell neuronal tracing, she found that the inhibitory signal that arrives to MNTB comes not only from outside source but also from the inside collateral neurons. Interestingly, the outside source of inhibition to MNTB, a small auditory brainstem nucleus in the medial olivocochlear center projects to the inner ear hair cells, where it too provides inhibition. This system of auditory brainstem – hair cells innervation changes within a life span. To further understand the role the medial olivocochlear center might have in age related hearing loss, Dr. Dondzillo research is focused on the inner ear hair cells and their synapses.
Dr. Dondzillo, in collaboration with Dr. Gubbels' lab, is interested in stem cell based hair cell regeneration in the cochlea after hair cell loss. To ablate inner ear hair cells we use genetically modified mouse model that expresses human diphtheria toxin receptor under the control of Pou4f3 gene. The Pou4f3 in the inner ear is expressed only in the hair cells and is responsible for hair cell maintenance. This time-and-cell-type precise ablation of hair cells allows to deliver stem cells into the cochlea at specific mouse ages and to observe distribution and differentiation of injected cells in the organ of Corti. In a related project, we use another genetic model mouse that expresses GFP under Nestin gene promoter. Nestin expressing cells have been found to act as progenitor cells in the central nervous system, therefore it is important to understand their role in the cochlea in general, and the organ of Corti in particular. Finally the combination of both of these mouse models provides us with the well-controlled ablation of inner ear hair cells with the ability to track nestin-expressing cells’ at various ages. These ongoing projects will be able to identify best time-windows for stem cells delivery to ensure optimal regeneration in the organ of Corti, if such optimal time exists. And secondly to better understand the role/s nestin, expressed by progenitor cells, but also expressed by astrocytes close to injury sites in the CNS plays in the organ of Corti after hair cell death in mice of different ages.
In another collaboration with Dr. Tollin Lab, Dr. Dondzillo is investigating the effects a very brief and loud sound stimulus, mimicking a blast, have on the inner ear hair cells’ synaptic connections. In this series of experiments a chinchilla model of blast induced hearing loss is used to best approximate the effects a sound blast has on human. Sound blast can trigger hair cell death, but it also could induce loss of the synapses without immediate loss of hair cells, a phenomenon termed as hidden hearing loss. The degree and the time period within which hair cell synapses are lost, and whether they regenerate after this type of auditory insult are not well understood.
Samuel P. Gubbels, MD, Associate Professor (Department of Otolaryngology)
Daniel Tollin, PhD (Physiology and Biophysics)
Sue Kinnamon, PhD; Tom Finger, PhD (Rocky Mountain Taste and Smell Center)
Dondzillo A, Klug A, Lei TC, Patent No: US 9,458,420 B2, System and methods for conducting in vitro experiment. Date of Patent Oct. 4 2016.