Dopaminergic modulation of low- and high spontaneous rate-type I auditory nerve fiber activity

Deflections of inner hair cell (IHC) stereocilia in response to sound trigger glutamate release from cochlear IHCs, which initiates action potential firing in auditory nerve fibers (ANFs) via IHC/ANF synapses. Physiological subgroups of ANFs exist, whereby low-spontaneous rate ANFs (low-SR ANFs) contact IHCs preferentially on the modiolar side, and high-SR ANFs on the pillar side. Efferent lateral olivocochlear (LOC) neurons originating in the brainstem terminate in the cochlea and release neuro-modulatory transmitters onto ANF endings close to their contact with IHCs. Of these transmitters, dopamine has been shown to reduce ANF firing rates. Here, it was examined whether dopamine and D1-like and D2-like dopamine receptor agonists affect low- and high-SR fibers differently, by monitoring SRs from bouton endings of post-hearing rat-cochlear-coils with extracellular loose patch recordings. In genetic reporter mouse models, the expression of DRD1 and DRD2 dopamine receptor genes was investigated in the cochlea. Dopamine and a D1-like receptor agonist reduced SR of both low- and high-SR ANFs, and this effect was blocked by a D1-like receptor antagonist. A D2-like agonist did not show similar inhibition, but the data cannot fully exclude a possible effect of D2-like receptors. Reporter mouse models suggest expression of the gene for the D1 receptor in both ANFs and efferent LOC neurons, whereas the gene for the D2 receptor was found only in efferent LOC neurons in the apex of the cochlea. These data provide evidence that dopamine inhibits all ANF subtypes through D1-like receptors.