A novel effect of cochlear efferents: in vivo response enhancement does not require alpha9 cholinergic receptors

Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes the effector arm of a sound-evoked negative feedback loop. The well-studied suppressive effects of acetylcholine (ACh) release from efferent terminals are mediated by alpha9/alpha10 ACh receptors and are potently blocked by strychnine. Here, we report a novel, efferent-mediated enhancement of cochlear sound-evoked neural responses and otoacoustic emissions in mice. In controls, a slow enhancement of response amplitude to supranormal levels appears after recovery from the classic suppressive effects seen during a 70-s epoch of efferent shocks. The magnitude of post-shock enhancement can be as great as 10 dB and tends to be greater for high-frequency acoustic stimuli. Systemic strychnine at 10 mg/kg eliminates efferent-induced suppression, revealing a purely enhancing effect of efferent shocks, which peaks within 5 s after efferent-stimulation onset, maintains a constant level through the stimulation epoch, and slowly decays back to baseline with a time constant of approximately 100 s. In mice with targeted deletion of the alpha9 ACh receptor subunit, efferent-evoked effects resemble those in wild types with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported.