Acoustic trauma during the critical period of development alters the correct maturation of the auditory system

CASTAGNA, VC; DI GUILMI, MN; FUCHS, PAUL A.; ELGOYHEN, AB; GOMEZ CASTI, ME

Congreso; Congreso anual de la Sociedad de Neurociencias; 2023

The auditory system of many mammals develops after birth. Before the onset of hearing, inner hair cells (IHC) are innervated by auditory nerve fibers and transiently by neurons of the medial olivocochlear (MOC) system. During this period, IHCs exhibit periodic depolarization patterns inducing stereotyped bursts of action potentials that are transmitted to the auditory circuits in the brain and promote neuronal survival, physiological maturation, and the proper establishment of the tonotopic map. It has been proposed that the MOC system may be a modulator of this activity. In addition, it has an important role in the protection from noise-induced hearing loss in adult rodents. Here, we evaluated the function of this transient synapse and the consequences of an early acoustic exposure during this critical period by comparing the performance of two different mouse models: an ?9 nicotinic receptor subunit knock-out (KO; Chrna9 KO), which lacks cholinergic transmission between efferent neurons and hair cells; and a gain-of-function knock-in (KI; Chrna9L9’T KI) carrying an ?9 point mutation that leads to enhanced cholinergic activity. Exposure to loud noise at this early stage, in wild-type produced cochlear threshold shifts and a decrease in neural response amplitudes, together with the loss of ribbon synapses, which is indicative of cochlear synaptopathy. In contrast, the Chrna9L9’T KI was completely resistant to the same acoustic exposure protocol.