Principal Investigator


Avril Genene Holt (Genene) is currently an Associate Professor of Anatomy and Cell Biology at Wayne State University School of Medicine.  Her research in the field of auditory neuroscience has included studies of the anatomy, physiology, neurochemistry and gene expression of the central auditory system. 

Specifically, she has expertise in deafness related changes in the gene expression and production of neurotransmitters and ion channels in the auditory brainstem.  More recently Dr. Holt has expanded her research to include identifying and measuring correlates of tinnitus by measuring neuronal activity in central auditory pathways using imaging approaches. Her research has been focused on understanding the balance between neuronal excitation and inhibition.  The ultimate goal is to modulate neuronal excitability in an effort to reverse the maladaptive neuroplasticity frequently observed with conditions such as hearing loss or tinnitus. Often, Dr. Holt has employed the "Discovery Science" approach. This approach necessitates the ability to analyze large quantities of data in order to identify specific patterns or correlates. When implemented in her research program, the Discovery Science approach allows development of a blueprint for discovering key underlying mechanisms and thereby development of plausible treatment paradigms.

Identification of gene products with altered levels of expression or production following a change in auditory stimulation provide a basis for assessing mechanisms and determining therapeutic targets.  Her group was the first in the auditory field to use gene microarrays and real time PCR to identify activity dependent neurotransmitter related genes within the central auditory pathway. Dr. Holt has reported changes in both neurotransmitter and ion channel related genes. She has combined two novel techniques (manganese enhanced MRI and acoustic startle reflex testing) that allow assessment of changes in neuronal activity in specific regions within auditory nuclei during the progression of tinnitus. These two functional measures are fairly non-invasive and should be translatable to the clinic. In terms of modulating neuronal activity, Dr. Holt has used optogenetics in cochlear nucleus (CN) neurons to provide proof of principle that neurons in the CN can be transfected with opsins to allow light driven excitation and inhibition of activity. This is a highly relevant topic with clinical implications given our aging population, the increase in recreational exposure to noise, and the fact that tinnitus and hearing loss are the top two compensated disabilities for veterans. 

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Holt Laboratory - Molecular Anatomy of Auditory Related Central Systems (MARCS)