Central compensation of neural responses to cochlear synaptopathy can be supported by dendritic spine remodeling through elevated cGMP levels

Increasing evidence suggest the hearing loss as a leading cause of disability but also a significant risk factor for cognitive decline and dementia. Older individuals often struggle with speech understanding in noisy environments, which can be due to progressive cochlear synaptopathy (loss of synapses between the hair cells and the auditory nerve fiber). It was previously demonstrated that cochlear synaptopathy leads to poorer temporal auditory processing (e.g., auditory steady state responses, ASSRs). Yet, the temporal auditory processing was not necessarily attenuated, when reduced auditory input is centrally compensated through enhanced input/output function of auditory brainstem responses (neural gain). This is accompanied by a better hippocampal long-term potentiation (LTP) and long-term depression (LTD) adjustment and upregulation of brain-derived neurotrophic factor (BDNF). Here, we investigated the cyclic guanosine-monophosphate (cGMP) signaling pathway as a potential molecular target involving in the central auditory compensation mechanism. Mice were administered either with phosphodiesterase 9A inhibitor - elevating intracellular cGMP level - or a vehicle. Interestingly, we found that the central auditory adaption processes are supported by the structural remodeling which can be induced by elevated intracellular cGMP levels.