Auditory activity sustains adult neurogenesis and cognition through the locus coeruleus-norepinephrine system

Hearing loss has been considered as potentially the leading modifiable risk factor for cognitive decline and dementia, but the causal link between these two conditions remains unsolved. Here, we report that mice with specific ablation of cochlear outer hair cells display marked hearing loss, which in turn leads to cognitive impairment and defective adult hippocampal neurogenesis. Furthermore, we discover that the dentate gyrus receives auditory input through a neuraxis, which originates from glutamatergic neurons of the caudal pontine reticular nucleus (PnC^vGluT2) and relays via norepinephrinergic neurons of the locus coeruleus (LC^NEergic). Hearing loss diminishes PnC^vGluT2 to LC^NEergic neuronal afferents, thereby reducing norepinephrine levels. Notably, stimulating PnC^vGluT2 to LC^NEergic neuronal afferents rescues the defective neurogenesis and cognitive impairment caused by hearing loss. Therefore, our study establishes a causal relationship between hearing loss and cognitive decline and emphasizes the importance of hearing wellness in sustaining cognitive function.