Age-related hearing loss is linked to cognitive impairment, but the mechanisms that relate to these conditions remain unclear. Evidence shows that the activation of medial olivocochlear (MOC) neurons delays cochlear aging and hearing loss. Consequently, the loss of MOC function may be related to cognitive impairment. The α9/α10 nicotinic receptor is the main target of cholinergic synapses between the MOC neurons and cochlear outer hair cells. Here, we explored spatial learning and memory performance in middle-aged wild-type (WT) and α9-nAChR subunit knock-out (KO) mice using the Barnes maze and measured auditory brainstem response (ABR) thresholds and the number of cochlear hair cells as a proxy of cochlear aging. Our results show non-significant spatial learning differences between WT and KO mice, but KO mice had a trend of increased latency to enter the escape box and freezing time. To test a possible reactivity to the escape box, we evaluated the novelty-induced behavior using an open field and found a tendency towards more freezing time in KO mice. There were no differences in memory, ABR threshold, or the number of cochlear hair cells. We suggest that the lack of α9-nAChR subunit alters novelty-induced behavior, but not spatial learning in middle-aged mice, by a non-cochlear mechanism.

3rd Faculty of Medicine Charles University Ruská 87 100 00 Prague Czech Republic

Biomedical Neuroscience Institute Facultad de Medicina Universidad de Chile Santiago 8320328 Chile

Centro Avanzado de Ingeniería Eléctrica y Electrónica AC3E Universidad Técnica Federico Santa María Valparaíso 2390136 Chile

Departamento de Neurociencia Facultad de Medicina Universidad de Chile Santiago 8320328 Chile

Department of Otolaryngology Hospital Clínico Universidad de Chile Santiago 8320328 Chile

Instituto de Ciencias de la Salud Universidad de O'Higgins Rancagua 2841935 Chile

Interdisciplinary Program of Physiology and Biophysics Institute of Biomedical Sciences Faculty of Medicine Universidad de Chile Santiago 8320328 Chile

National Institute of Mental Health Topolová 748 250 67 Klecany Czech Republic

Otolaryngology Department School of Medicine Johns Hopkins University Baltimore MD 21231 USA

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