Hearing loss (HL) has become a worldwide problem. WHO estimates that the number of people worldwide with moderate or higher levels of HL could reach 700 million by 2050, up from the current 470 million (Chadha et al., 2021), and that auditory cognitive abnormalities associated with HL will become an increasingly severe problem in the future. The neuronal mechanism for auditory cognitive abnormalities in deafness is thought to be excessive neural activity within the auditory central nervous system caused by HL. When the input of sound information from the cochlea to the auditory pathway is reduced due to HL, in general, there is an excessive increase in neural activity in the auditory pathway to compensate for the reduced input (Gold and Bajo, 2014). This abnormal increase in neural activity is thought to produce auditory cognitive abnormalities (Auerbach et al., 2014; Richardson et al., 2012).

This review focuses on the abnormal neuronal activity in the inferior colliculus (IC) induced by HL. IC is the first auditory integration center located in the midbrain, receiving input from virtually all auditory brainstem nuclei (Fig. 1A) and driving the higher auditory centers. Since changes in the neuronal activity of IC neurons may strongly impact auditory cognition, clarifying the neuronal mechanisms underlying HL-induced changes in IC activity would be important for elucidating the neural mechanisms of auditory perceptual abnormalities caused by HL.

There can be multiple possible mechanisms for the activity changes of IC neurons induced by HL. First, as already mentioned, the IC is a place where inputs from the brainstem are integrated, so activity changes at the IC are likely to reflect afferent inputs from the brainstem. Second, in addition to the alteration in afferent activities, it is possible that some postsynaptic changes in excitability underlie activity changes after HL. Third, it is also possible that there are changes in inhibitory neurotransmission in the IC.

This review will describe in detail these HL-induced changes in the brainstem and IC and aim to elucidate how the HL-induced changes in IC activity are formed. Non-age-related deafferentation-induced HLs and age-related HLs, both of which are common causes of HL, will be described in separate sections. These HLs have both similarities and differences. Non-age-related HL is classified into conductive HL (CHL) and sensorineural HL (SNHL). CHL is caused by disorders of the external auditory canal or middle ear that interfere with the transmission of sound to the inner ear. On the other hand, SNHL is caused by impairment in the neuronal auditory pathway that originates in the cochlea. Age-related HL is considered a type of SNHL. Both non-age-related HLs and age-related HLs involve a decrease in the inputs through auditory nerves (ANs) to the central auditory pathway, caused by the impairment of the cochlea and ANs or sound transmission disorder. As a result, spontaneous activity in the central auditory pathway is increased in both types of HLs, although to varying degrees. Behind these changes, alterations in synaptic structure and pre- and post-synaptic ion channel expression are known to occur in both types of HLs (see the following sections). The difference between the two, however, is that age-related HL involves age-induced abnormality in the neurons and glia (e.g., DNA damage, mitochondrial instability, protein aggregation, etc) (Mattson and Magnus, 2006) in addition to cochlea damage by aging. Therefore, we will divide these two HLs into their own sections in order to describe them while clarifying their similarities and differences. Before discussing the HL-induced altered activity of IC neurons and its underlying mechanisms, we first briefly describe the neural circuit configuration of the IC, the animal models for HL, and changes in the structure and activity of AN after HL.