A discrete serotonergic circuit involved in the generation of tinnitus behavior.

Summary

Identified a serotonergic subpopulation in the dorsal raphe nucleus (DRN) that projects to the dorsal cochlear nucleus (DCN), a brainstem region whose hyperactivity is linked to tinnitus. Optogenetic activation of this 5-HT^DRN→DCN circuit increased DCN fusiform-cell spiking in a pattern consistent with tinnitus-like hyperactivity. Chemogenetic activation of the circuit induced tinnitus-related behavior in mice, largely reversed by blocking 5-HT2A receptors. Noise exposure itself raised DCN serotonin levels and 5-HT^DRN→DCN activity in mice with noise-induced tinnitus behavior, and chemogenetically inhibiting the circuit significantly reduced that behavior.

Key findings

• A discrete serotonergic DRN→DCN circuit was anatomically and functionally identified in mice.
• Optogenetic activation of the circuit increased DCN fusiform-cell spike activity, consistent with tinnitus-related hyperactivity.
• Chemogenetic activation induced tinnitus-related behavior, largely reversed by blocking 5-HT2A receptors.
• Noise exposure raised DCN serotonin levels and circuit activity, and chemogenetically inhibiting the circuit ameliorated noise-induced tinnitus behavior.