Abstract
Age-related hearing loss (ARHL) is associated with weakened inhibition in the central auditory nervous system including the cochlear nucleus. One of the main inhibitory neurons of the cochlear nucleus is the D-stellate neuron, which provides extensive glycinergic inhibition within the local neural network. It remains unclear how physiological activities of D-stellate neurons change during ARHL and what are the underlying mechanisms. Using in vitro whole-cell patch clamp technique, we studied the intrinsic membrane properties of D-stellate neurons, the changes of their firing properties, and the underlying mechanisms in CBA/CaJ mice at the ages of 3–4 months (young), 17–19 months (middle age), and 27–33 months (aged). We found that the intrinsic membrane properties of D-stellate neurons were unchanged among these three age groups. However, these neurons showed decreased firing rate with age in response to sustained auditory nerve stimulation. Further investigation showed that auditory nerve-evoked excitatory postsynaptic currents (EPSCs) were significantly reduced in strength with age. These findings suggest that D-stellate neurons receive weakened synaptic inputs from the auditory nerve and decreased sound driven activity with age, which are expected to reduce the overall inhibition and enhance the central gain in the cochlear nucleus during ARHL.
Highlights
The cochlear nucleus (CN) is the first neural station in the central auditory pathway that processes all sound information from the periphery auditory nerve and projects to higher auditory nuclei [1]
In order to test the hearing status of the CBA/CaJ mice in this study, we measured the auditory brainstem response (ABR) from all mice in three age groups to clicks at sound levels from 20 to 90 dB SPL
Hearing thresholds could not be determined from five aged mice because no clear ABR waveforms were evoked by clicks at even the highest tested level of 90 dB SPL
Summary
The cochlear nucleus (CN) is the first neural station in the central auditory pathway that processes all sound information from the periphery auditory nerve and projects to higher auditory nuclei [1]. One of the major CN inhibitory interneurons is the D-stellate neuron in the ventral cochlear nucleus (VCN) [14,15,16,17,18]. They receive excitatory inputs from the auditory nerve, and provide glycinergic inhibition locally within the VCN and to the dorsal cochlear nucleus (DCN) [5,17,19,20,21], as well as to the contralateral CN [15,22,23].
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