Dr Stuart Johnson
Royal Society University Research Fellow
Room: B1 220 Alfred Denny building
Brief career history
Signalling characteristics of cochlear hair cells
Auditory neuroscience, Sensory coding, Synaptic transmission
Mammalian cochlear inner hair cells (IHCs) are the primary sensory cells of the auditory pathway. Their job is to convert sound vibrations into an electrical signal that can be interpreted by the brain. As such, it is vital that the information encoded by IHCs is accurately preserved at this initial stage. One of the major causes of deafness/hearing loss is associated with IHCs losing their ability to function normally.
The aim of my research is to find out how IHCs are able to accurately encode sounds over a wide frequency and intensity range and how the information is processed on its way to the brain. Knowledge of how the ear processes sound will be informative to develop improved hearing aids, including cochlear implants. An additional aspect of my research applies directly to define how stem cells are able to replace damaged nerve fibres in order to restore hearing (in collaboration with Prof Marcelo Rivolta).
In order to achieve this I will study IHCs in the isolated cochlea using a combination of electrophysiological, cell imaging and molecular biological techniques.
Undergraduate and postgraduate taught modules
PhD Studentship starting October 2017
Title: Exploring re-innervation and synaptogenesis between human stem cell-derived auditory neurons and inner hair cells: A therapeutic model for ‘hidden hearing loss’
Supervisors: Professor Marcelo Rivolta and Dr Stuart Johnson
Finding: Competition funded project European/UK students only.
Loud noise exposure and aging lead to the permanent loss of afferent synaptic contacts to the primary sensory inner hair cells (IHCs) in the cochlea, whilst causing only a temporary or undetectable hearing threshold shift. This ‘synaptopathy’ reduces IHC afferent innervation by up to 50% leaving an individual unable to detect sounds in a noisy environment and experiencing difficulties with speech discrimination and intelligibility. Since the hearing thresholds are unaltered, it is difficult to detect the condition using conventional hearing tests, hence it is named ‘hidden hearing loss’. The loss of synaptic contacts is also thought to underlie primary neural degeneration in acquired hearing loss and aging.
The causative mechanisms underlying cochlear synaptopathy are not well understood. While it is believed to be a result of the toxic effects of overstimulating these fibres, it is not known whether there are any changes in the properties of the IHCs that lead to axonal retraction or, conversely, whether there are any IHC changes that result from it.
We have previously shown that human embryonic stem cell-derived spiral ganglion neurons (SGNs) can be transplanted into an animal model and establish synaptic connections and recovery of function. To address the specific role of the afferent fibres the student will learn to co-culture the adult gerbil organ of Corti with hESC-derived SGNs to see if the IHC properties have changed in order to attract new fibres and/or whether new synaptic innervation of the hair cells can restore their mature phenotype.
This study will allow us to understand the chain of events that lead to the ‘de-differentiation’ of IHCs in culture and whether it can be reversed by re-innervation from stem cell-derived SGNs. The advantages of using the mature organotypic culture as a model system to study IHC and afferent fibre synaptopathy, and cochlear plasticity in general, are that the conditions can be easily manipulated whilst monitoring the characteristics of the IHCs and afferent fibres throughout.
Keywords: Biophysics, Cell Biology / Development, Molecular Biology, Neuroscience / Neurology, Biophysics
Further information about this project can be found on our PhD Opportunities page:
- Johnson SL, Olt J, Cho S, von Gersdorff H & Marcotti W (2017) The coupling between Ca2+ channels and the exocytotic Ca2+ sensor at hair cell ribbon synapses varies tonotopically along the mature cochlea.. Journal of Neuroscience. View this article in WRRO
- Johnson SL (2015) Membrane properties specialize mammalian inner hair cells for frequency or intensity encoding. eLife, 4. View this article in WRRO
- Corns LF, Johnson SL, Kros CJ & Marcotti W (2014) Calcium entry into stereocilia drives adaptation of the mechanoelectrical transducer current of mammalian cochlear hair cells. Proceedings of the National Academy of Sciences, 111(41), 14918-14923.
- Johnson SL, Wedemeyer C, Vetter DE, Adachi R, Holley MC, Elgoyhen AB & Marcotti W (2013) Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses.. Open Biol, 3(11). View this article in WRRO
- Johnson SL, Kuhn S, Franz C, Ingham N, Furness DN, Knipper M, Steel KP, Adelman JP, Holley MC & Marcotti W (2013) Presynaptic maturation in auditory hair cells requires a critical period of sensory-independent spiking activity.. Proc Natl Acad Sci U S A, 110(21), 8720-8725.
- Johnson SL, Kennedy HJ, Holley MC, Fettiplace R & Marcotti W (2012) The resting transducer current drives spontaneous activity in prehearing mammalian cochlear inner hair cells.. J Neurosci, 32(31), 10479-10483.
- Johnson SL, Beurg M, Marcotti W & Fettiplace R (2011) Prestin-driven cochlear amplification is not limited by the outer hair cell membrane time constant.. Neuron, 70(6), 1143-1154.
- Johnson SL, Eckrich T, Kuhn S, Zampini V, Franz C, Ranatunga KM, Roberts TP, Masetto S, Knipper M, Kros CJ & Marcotti W (2011) Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.. Nature Neuroscience, 14(6), 711-717. View this article in WRRO
- Johnson SL, Franz C, Kuhn S, Furness DN, Rüttiger L, Münkner S, Rivolta MN, Seward EP, Herschman HR, Engel J, Knipper M & Marcotti W (2010) Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses.. Nat Neurosci, 13(1), 45-52.