The role of brevican in cochlear function and normal hearing through its interaction with hair cells and bone

• Applicant: Dr. Mandy Sonntag
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 462309424

The central nervous system (CNS) is composed of neurons and glia cells as well as extracellular matrix (ECM). The ECM is composed of specific macromolecules which fill the extracellular spaces between the cells and accounts for up to 20% of brain volume. There is increasing evidence that the ECM is an essential determinant of the organization and function of the CNS. Perineuronal nets (PNs) and their constructive chondroitin sulfate proteoglycans are classified as a unique and specialized composition of the ECM. PNs surround the cell bodies, dendrites and axon initial segments of a particular subset of neurons. PNs are associated with a large range of functions, including neuronal protection, restriction of synaptic plasticity, regulation of developmental processes and control of synaptic transmission and neuronal activity. It is further assumed that individual PN components account for the different functions of PNs. Brevican as one of the main proteoglycans of PNs is involved in the maintenance of high speed of synaptic transmission in the auditory brainstem and is essential for normal hearing. Brevican was supposed to be CNS-specific but we could recently provide evidence that brevican is also present in the cochlea, forming extracellular baskets around inner hair cells which are supposed be the peripheral version of central PNs. Interestingly, brevican is further expressed at the otic capsule, delineating the border between bone and 'soft' tissue of the cochlea, and in the osseous spiral lamina. The function of bone-associated brevican in the cochlea remains unknown. The main scope of this proposal is studying the role of brevican in the cochlea and two unravel why brevican is expressed both at inner hair cells and at bony structures. We will focus on structural and molecular features as well as physiological and functional aspects. Through the combination of immunohistochemical, biochemical, molecular, physiological, and high-resolution imaging techniques we will be able to expand our knowledge on brevican and its role in cochlear function and normal hearing.

• DFG Programme: Research Grants