Research in the lab
General Introduction:
Hearing is a sense that is often taken for granted and hearing loss is generally accepted as just another result of getting older. Despite these preconceptions, the sense of hearing is fundamental for human well-being and the auditory system faces some of the most stringent biological demands to properly function. Despite the importance of the auditory system, much of the underlying biology of hearing remains unknown and treatment options for hearing loss and other auditory pathologies such as tinnitus remain extremely limited. This lack of knowledge largely arises because it is hard to study the sensory hair cells and their auditory neurons, the auditory nerve fibers. The goal of the Glowatzki lab is to study some of the fundamental mechanisms that underlie the function of these hair cells and the auditory nerve fibers under normal and pathological conditions.
Current research topics:
1: Subgroup identification of the auditory nerve fiber responses
One of the difficulties in studying the auditory system is that there is much variation and specialization in both the sensory cells and the auditory nerve fibers that carry information from the hair cells to the brain. In order to respond to sounds with frequencies ranging between 20 Hz and 20 kHz and sound intensities between 0 and 130 decibels, the sensory cells and their neurons form subgroups with subtle differences that respond to sounds of a specific frequency and intensity. The Glowatzki lab is working on identifying these subgroups and describing the subtle differences that shape these subgroups. We study these subgroups by acquiring extracellular and intracellular patch clamp recordings of these auditory neurons as one of a few labs capable of doing these recordings.
2: Regeneration of synaptic function in the auditory periphery.
The classic idea about hearing loss is that the sensory hair cells need to be damaged to develop hearing loss. In the last decade or so it has become apparent that hearing loss can arise from the destruction of the auditory nerve fibers prior to loss of the hair cells. Therefore, the ability to regenerate these auditory nerve fibers is considered a possible treatment option for hearing loss. Together with Dr. Albert Edge (Harvard university, Eaton Peabody laboratories) we are investigating how the auditory neurons that connect to the hair cells can be restored after hair cell or auditory nerve fiber loss (Martinez-Monedero et al., 2008). By using stem cells it is now possible to regenerate these auditory neurons at least in vitro and we are studying whether these newly formed neurons regain all the properties of normal auditory neurons. These newly formed neurons must be similar to normal auditory neurons to be effectively used as a treatment option.
3: Efferent synaptic transmission in the mammalian cochlea.
The activity of the hair cells and the auditory nerve fibers is shaped by a set of efferent neurons that provide feedback from the brain to the auditory system. These efferent neurons are thought to be both stimulating and inhibiting depending on the needs of the auditory system. The inhibiting branch of this system is dependent on the neurotransmitter dopamine. We have shown that dopamine can reduce the activity of the auditory neurons that contact the hair cells (Wu et al., 2020). Current work focuses on looking at the effect of dopamine on the different subgroups of auditory nerve fibers and on the stimulating branch of the efferent neurons that is dependent on the neurotransmitter acetylcholine.
4: Changes in the auditory system following noise expsure
In collaboration with Amanda Lauer (Lauer lab Johns Hopkins Medical School), we are investigating what changes occur to the hair cells and auditory nerve fibers following noise exposure and during ageing. We have shown that the expression of TH (a precursor for dopamine) is upregulated in efferent neurons in animals that have been exposed to loud sounds (Wu et al., 2020). Thus, the auditory system is a plastic system in response to noise rather than a static one. We are currently studying which mechanisms are plastically regulated in response to sound and by which mechanisms they affect the function of the auditory system.