Bidirectional Regulation of Innate and Learned Behaviors That Rely on Frequency Discrimination by Cortical Inhibitory Neurons

The ability to discriminate tones of different frequencies is fundamentally important for everyday hearing. While neurons in the primary auditory cortex (AC) respond differentially to tones of different frequencies, whether and how AC regulates auditory behaviors that rely on frequency discrimination remains poorly understood. Here, we find that the level of activity of inhibitory neurons in AC controls frequency specificity in innate and learned auditory behaviors that rely on frequency discrimination. Photoactivation of parvalbumin-positive interneurons (PVs) improved the ability of the mouse to detect a shift in tone frequency, whereas photosuppression of PVs impaired the performance. Furthermore, photosuppression of PVs during discriminative auditory fear conditioning increased generalization of conditioned response across tone frequencies, whereas PV photoactivation preserved normal specificity of learning. The observed changes in behavioral performance were correlated with bidirectional changes in the magnitude of tone-evoked responses, consistent with predictions of a model of a coupled excitatory-inhibitory cortical network. Direct photoactivation of excitatory neurons, which did not change tone-evoked response magnitude, did not affect behavioral performance in either task. Our results identify a new function for inhibition in the auditory cortex, demonstrating that it can improve or impair acuity of innate and learned auditory behaviors that rely on frequency discrimination.分辨不同频率音调的能力对于日常听觉至关重要。尽管初级听觉皮层（primary auditory cortex, AC）内的神经元可对不同频率的音调产生差异化响应，但该皮层是否以及如何调控依赖频率分辨的听觉行为，目前仍知之甚少。本研究发现，初级听觉皮层内抑制性神经元的活动水平，可调控依赖频率分辨的先天与习得听觉行为中的频率特异性。对小白蛋白阳性中间神经元（parvalbumin-positive interneurons, PVs）进行光激活（photoactivation），可提升小鼠检测音调频率偏移的能力；而对PVs进行光抑制（photosuppression）则会损害其行为表现。此外，在分辨性听觉恐惧条件反射过程中对PVs进行光抑制，会增加条件化反应在不同音调频率间的泛化程度；而PV光激活则可维持学习的正常特异性。所观察到的行为表现变化与音调诱发反应幅度的双向变化呈显著相关，这与兴奋-抑制耦合皮层网络模型的预测相符。直接光激活兴奋性神经元并不会改变音调诱发反应的幅度，因此不会对两项任务中的行为表现产生影响。本研究结果明确了听觉皮层内抑制作用的新功能，证实其可改善或损害依赖频率分辨的先天及后天习得听觉行为的敏锐度。