Professor Walter Marcotti
Professor of Sensory Neuroscience
Room: B1 221 Alfred Denny building
Brief career history
Awards and prizes
Auditory neuroscience and Deafness Sensory transduction Synaptic transmission
Sensory organs and the neural networks responsible for processing sensory information are supremely well adapted for detecting input from the external environment. Their challenge is to maximize sensitivity and fidelity over a wide dynamic range. The sensory receptors of the mammalian auditory system, the inner hair cells (IHCs), do this with unparalleled temporal precision (kHz range). We know little about the molecular and physiological mechanisms controlling the functional maturation of the auditory system or signal processing at the primary auditory synapses, the IHC ribbon synapses. Crucial to this work, is the need of near-physiological in vitro and the development of in vivo experimental models.
My laboratory is uniquely suited for this task because it is the only one in the world that routinely uses near-physiological conditions for in vitro mammalian cochlear physiology and performs in-vivo electrophysiology from the zebrafish. How biological systems orchestrate their development and how complex signals are processed by mature neuronal networks are major challenges in the quest to understand human biology and disease.
The auditory system provides an ideal model with which to address these questions, primarily because it involves a highly ordered array of a very small number of sensory cells with well-defined neuronal circuitry. It is also a key priority for human health because hearing loss affects more than 360 million people worldwide (WHO 2013), a number that will increase with the aging population.
Undergraduate and postgraduate taught modules
Title: Understanding the functional role of adhesion molecules in the synaptogenesis of ribbon synapses in mammalian auditory system
Supervisor 1: Professor Walter Marcotti
Supervisor 2: Dr Steve Brown (MRC Harwell)
Funding status: Competition funded project European/UK students only
This project is eligible for a department scholarship. These scholarships are awarded on a competitive basis – find out more on our funding webpage.
Hearing is profoundly important in order to perceive information from the outside world and its loss can have a dramatic impact on our daily lives. The perception of hearing depends on the transduction of sound waves into an electrical signal in the auditory organ, the cochlea, which is then transmitted to the brain via auditory afferent neurons. Crucial to this physiological process is the precise, rapid and continuous release of the neurotransmitter glutamate from highly specialized ribbon synapses at the basolateral membrane of sensory inner hair cells (IHCs) located in the mammalian cochlea, which are juxtaposed to the afferent auditory terminals.
We have recently shown that a mutation that affects Neuroplastin caused a failure in the normal synaptogenesis of ribbon synapses in IHCs (Carrott et al 2016). Neuroplastin is a member of the Basigin group of neuronal and synapse-enriched glycoproteins belonging to the immunoglobulin (Ig) superfamily of neural cell adhesion molecules (CAMs), which also includes Basigin and Embigin. All these CAMs are expressed in the mammalian cochlea. Currently, we lack any understanding on the role of Basigin and Embigin on hearing function, as well as the specific involvement of the two encoded Neuroplastin protein isoforms - Neuroplastin-65 and Neuroplastin-55. We will use a combination of well-established and state-of-the-art techniques, together with transgenic mouse models lacking these CAMs to address the hypothesis that this group of proteins is crucial not only for the acquisition, but also for the maintenance of IHC ribbon synapses in hair cells, and as such playing a primary role in hearing. We will also test the hypothesis that these genes are involved age-related hearing loss.
The project will involves a collaboration between the laboratories of Prof Walter Marcotti (Wellcome Trust Senior Investigator, University of Sheffield) and Prof. Steve Brown and Dr Mike Bowl (Director and Project leader, respectively, at the MRC Harwell Institute) who are world-wide experts in hearing and also in the different aspects of this project. You will be trained in a wide-range of in vitro and in vivo techniques, such as patch clamping and 2-photon confocal microscopy, together with the latest techniques in gene expression and mouse genetics. You will also benefit greatly from the wide range of expertise present in the two Institutions through joint lab meeting that are held on a regular basis.
You will complete your PhD having gained a wide range of highly desirable skills, providing a firm foundation for a career in academia or industry.
Keywords: Biophysics, Cell Biology / Development, Genetics, Neuroscience/Neurology, Biophysics
Carrott, L., et al., (2016) Absence of neuroplastin-65 affects synaptogenesis in mouse inner hair cells and causes profound hearing koss. J Neurosci, 36: 222-34.
For informal enquiries about the project or application process, please feel free to contact:
For further information about these projects and how to apply, see our PhD Opportunities page:PhD Opportunities
- 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, 37(9), 2471-2484. View this article in WRRO
- Johnson SL, Ceriani F, Houston O, Polishchuk R, Polishchuk E, Crispino G, Zorzi V, Mammano F & Marcotti W (2017) Connexin-Mediated Signaling in Nonsensory Cells Is Crucial for the Development of Sensory Inner Hair Cells in the Mouse Cochlea.. J Neurosci, 37(2), 258-268. View this article in WRRO
- Olt J, Allen CE & Marcotti W (2016) In vivo physiological recording from the lateral line of juvenile zebrafish.. Journal of Physiology, 594(19), 5427-5438. View this article in WRRO
- Corns LF, Johnson SL, Kros CJ & Marcotti W (2016) Tmc1 Point Mutation Affects Ca2+ Sensitivity and Block by Dihydrostreptomycin of the Mechanoelectrical Transducer Current of Mouse Outer Hair Cells. Journal of Neuroscience, 36(2), 336-349. 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.
- Furness DN, Johnson SL, Manor U, Rüttiger L, Tocchetti A, Offenhauser N, Olt J, Goodyear RJ, Vijayakumar S, Dai Y, Hackney CM, Franz C, Di Fiore PP, Masetto S, Jones SM, Knipper M, Holley MC, Richardson GP, Kachar B & Marcotti W (2013) Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2.. Proc Natl Acad Sci U S A, 110(34), 13898-13903.