VAMPHEARS

By 2050, 900 million people will be affected by hearing disorders, mostly age-related hearing loss owing to the aging of the world population and the increasing exposure to noise. Hearing loss deeply modifies the neuronal activity of auditory networks, but less attention has been given to its effects on the brain vascular network. The need for speed and temporal accuracy of the auditory system results in a high metabolic demand. A correlate of this need is that the auditory system is highly vulnerable to changes in oxygen and glucose supply, and is probably sensitive to the “health” of the vascular network. We have obtained ground-breaking preliminary results showing that i) the central auditory system is highly vascularised and ii) this vascularisation is strongly remodelled following peripheral hearing loss. However, the mechanisms by which neuronal activity interfaces with the addition of capillary branches in early postnatal stages and how changes in neuronal activity following hearing loss affect the development and maintenance of the vascular network, are unknown. By combining our recent methodological progress in reconstructing the 3D organization of the vaculature at the scale of the entire brain (partner 1), our expertise in mouse models of deafness mimicking different types of auditory deficits (partner 2), and methods of hearing restoration (partner 3), we aim to determine how hearing impairment affects the vascular organisation of the central auditory system and to decipher the underlying mechanisms. The “VAMPHEARS” (VAscular Modelling and Plasticity of the HEARing System) project will address in mice: (1) What are the specific developmental stages of the auditory vascular system and how does deafness affect them? We will compare the impact of congenital and progressive hearing loss on the topology of the micro-vasculature in the whole brain, using genetic models of hearing loss with different onsets. We aim to study the vascular changes not only in the auditory relays, but also in other brain regions heavily connected to the auditory system. (2) What are the vascular remodeling mechanisms in the adult brain following hearing loss? Following transcriptomic preliminary data we obtained, we will assess the cellular changes and damages induced by vascular remodelling following hearing loss with a specific focus on the microglia, mural cells and pericytes. (3) Are these deficits reversible upon hearing restoration? We will assess whether two paradigms of hearing restoration, a) gene therapy for a congenital genetic form of deafness and b) direct electrical activation of the auditory nerve, may rescue auditory system vascularisation deficits. From a fundamental standpoint, «VAMPHEARS» will establish whether hearing loss is detrimental to the vascular network and address a long-standing controversy regarding the potential of the adult vascular network to undergo activity-dependent structural plasticity. By determining whether cerebrovascular deficits can be reversed by hearing restoration, this work will provide a scientific basis for improving auditory rehabilitation in patients.