La inhibición de HDAC3 aprovecha los mecanismos neurobiológicos inducidos por el aprendizaje para mejorar la...

Auditory learning enables sound-guided behavior and sound-specific enhancements in auditory cortical (AC) processing. Background noise can also alter sound-specific auditory responsivity. Yet, the potential enhancing effects of learning on AC processing in noise is unknown. Pharmacological inhibition of histone deacetylase 3 (HDAC3) by RGFP966 has been shown to improve AC coding when administered during various auditory learning paradigms. Here, adult rats (Sprague-Dawley males) were trained in ideal quiet conditions to learn a tone-reward associative task while treated with RGFP966 (TRAINED+RGFP966, n = 6) to determine if learning-related effects on AC could support tone-signal detection in a later background noise challenge. RGFP966 accelerated sound-reward learning relative to a trained but untreated group of rats (TRAINED, n = 5), though all animals ultimately reached equivalent high levels of performance prior to testing. Training produced a sound-specific enhancement in AC responses evoked by the signal tone, and a sound-general effect that suppressed responses during steady-state noise, relative to untrained rats (NAÏVE, n = 7). Effects were strongest when training was with RGFP966 administration and scaled with increasing signal-to-noise (SNR). High levels of background noise abolished sound-specific enhancements in tone-signal evoked AC activity, yet the general suppressive effect to noise was maintained. Remarkably, behavioral responses to the signal tone in different SNRs recapitulated AC patterns of tone-evoked responding. Overall, rapid auditory learning facilitated by RGFP966 yields AC plasticity that can improve signal detection. Learning-induced mechanisms appear to shape cortical decoding mechanisms that selectively enhance representations of signal sounds and suppress the effects of background noise.

Difficulty hearing in noise is a widespread challenge, yet the cortical mechanisms that preserve meaningful sounds under noisy listening conditions remain unclear. We show that HDAC3 inhibition accelerates auditory learning and strengthens cortical encoding of a learned tone while suppressing background noise activity in ways that predict improved behavioral detection. These findings reveal an experience-driven cortical mechanism that supports improved hearing in challenging listening environments, which may inform strategies for enhancing auditory learning and rehabilitation using HDAC3 drug-targets.