Enhanced auditory gain and tinnitus-like behavior in mice lacking KCTD12, an auxiliary subunit of GABA(B) receptors

Precise regulation of neural gain is essential for accurate sensory processing and relies on inhibitory mechanisms that constrain neuronal responsiveness. Disruption of inhibitory control has been implicated in disorders characterized by abnormal sensory perception, including tinnitus, yet the molecular mechanisms regulating inhibitory signaling remain poorly understood....

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This is an animal model study; no actionable change to clinical practice is warranted, but it advances understanding of inhibitory pathways that may be targeted in future tinnitus therapies.

Pinpointing KCTD12 as a regulator of auditory gain through GABA(B) receptor signaling opens a new molecular target for tinnitus research and potential drug development.

1. 01Mice lacking KCTD12 (an auxiliary subunit of inhibitory GABA(B) receptors) showed enhanced auditory gain — exaggerated hearing responses.
2. 02These mice also exhibited tinnitus-like behavior, suggesting a link between reduced inhibition and phantom sound perception.
3. 03GABA(B) receptor signaling is implicated as a key inhibitory pathway in auditory gain control.
4. 04Published in Neurobiology of Disease; findings are preclinical and not directly translatable to humans yet.
5. 05KCTD12 may be a novel molecular target for future tinnitus treatments.

PMID

42946148

DOI

10.1016/j.nbd.2026.107664.

Journal

Neurobiology of Disease

Publication type

research_article

Evidence level

4

Population

KCTD12 knockout mice (animal model)

Intervention

Genetic deletion of KCTD12 (auxiliary GABA(B) receptor subunit)

Comparator

Wild-type control mice