Masri Samer, Fair Regan, Mowery Todd M, Sanes Dan H
Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003.
Brain Health Institute & Department of Otolaryngology, Rutgers University.
bioRxiv. 2023 Jan 10:2023.01.10.523440. doi: 10.1101/2023.01.10.523440.
Even transient periods of developmental hearing loss during the developmental critical period have been linked to long-lasting deficits in auditory perception, including temporal and spectral processing, which correlate with speech perception and educational attainment. In gerbils, hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABA and metabotropic GABA receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABA receptors. We developed viral vectors to express both endogenous GABA or GABA receptor subunits in auditory cortex and tested their capacity to restore perception of temporal and spectral auditory cues following critical period hearing loss in the Mongolian gerbil. HL significantly impaired perception of both temporal and spectral auditory cues. While both vectors similarly increased IPSCs in auditory cortex, only overexpression of GABA receptors improved perceptual thresholds after HL to be similar to those of animals without developmental hearing loss. These findings identify the GABA receptor as an important regulator of sensory perception in cortex and point to potential therapeutic targets for developmental sensory disorders.
即使在发育关键期出现短暂的发育性听力损失，也与听觉感知的长期缺陷有关，包括时间和频谱处理，这些缺陷与言语感知和学业成就相关。在沙鼠中，听力损失引起的感知缺陷与听觉皮层中离子型GABA和代谢型GABA受体介导的突触抑制的减少有关，但大多数关于关键期可塑性的研究都集中在GABA受体上。我们开发了病毒载体，用于在听觉皮层中表达内源性GABA或GABA受体亚基，并测试了它们在蒙古沙鼠关键期听力损失后恢复时间和频谱听觉线索感知的能力。听力损失显著损害了时间和频谱听觉线索的感知。虽然两种载体同样增加了听觉皮层中的抑制性突触后电流，但只有GABA受体的过表达改善了听力损失后的感知阈值，使其与没有发育性听力损失的动物相似。这些发现确定了GABA受体是皮层感觉感知的重要调节因子，并指出了发育性感觉障碍的潜在治疗靶点。
