Ear Institute, University College London, London, WC1X 8EE, United Kingdom
Ear Institute, University College London, London, WC1X 8EE, United Kingdom.
J Neurosci. 2023 Feb 1;43(5):749-763. doi: 10.1523/JNEUROSCI.1426-22.2022. Epub 2023 Jan 5.
A key question in auditory neuroscience is to what extent are brain regions functionally specialized for processing specific sound features, such as location and identity. In auditory cortex, correlations between neural activity and sounds support both the specialization of distinct cortical subfields, and encoding of multiple sound features within individual cortical areas. However, few studies have tested the contribution of auditory cortex to hearing in multiple contexts. Here we determined the role of ferret primary auditory cortex in both spatial and nonspatial hearing by reversibly inactivating the middle ectosylvian gyrus during behavior using cooling ( = 2 females) or optogenetics ( = 1 female). Optogenetic experiments used the mDLx promoter to express Channelrhodopsin-2 in GABAergic interneurons, and we confirmed both viral expression ( = 2 females) and light-driven suppression of spiking activity in auditory cortex, recorded using Neuropixels under anesthesia ( = 465 units from 2 additional untrained female ferrets). Cortical inactivation via cooling or optogenetics impaired vowel discrimination in colocated noise. Ferrets implanted with cooling loops were tested in additional conditions that revealed no deficit when identifying vowels in clean conditions, or when the temporally coincident vowel and noise were spatially separated by 180 degrees. These animals did, however, show impaired sound localization when inactivating the same auditory cortical region implicated in vowel discrimination in noise. Our results demonstrate that, as a brain region showing mixed selectivity for spatial and nonspatial features of sound, primary auditory cortex contributes to multiple forms of hearing. Neurons in primary auditory cortex are often sensitive to the location and identity of sounds. Here we inactivated auditory cortex during spatial and nonspatial listening tasks using cooling, or optogenetics. Auditory cortical inactivation impaired multiple behaviors, demonstrating a role in both the analysis of sound location and identity and confirming a functional contribution of mixed selectivity observed in neural activity. Parallel optogenetic experiments in two additional untrained ferrets linked behavior to physiology by demonstrating that expression of Channelrhodopsin-2 permitted rapid light-driven suppression of auditory cortical activity recorded under anesthesia.
听觉神经科学的一个关键问题是，大脑区域在多大程度上专门用于处理特定的声音特征，如位置和身份。在听觉皮层中，神经活动与声音之间的相关性既支持了不同皮质亚区的专业化，也支持了单个皮质区域中多个声音特征的编码。然而，很少有研究测试听觉皮层在多种情况下对听觉的贡献。在这里，我们通过在行为过程中使用冷却（= 2 只雌性）或光遗传学（= 1 只雌性）可逆地使中间外侧乙状回失活，来确定雪貂初级听觉皮层在空间和非空间听觉中的作用。光遗传学实验使用 mDLx 启动子在 GABA 能中间神经元中表达 Channelrhodopsin-2，我们在麻醉下使用 Neuropixels 记录时，验证了病毒表达（= 2 只雌性）和光驱动对听觉皮层尖峰活动的抑制（= 465 个单位，来自另外 2 只未经训练的雌性雪貂）。通过冷却或光遗传学的皮层失活会损害在共定位噪声中的元音辨别。植入冷却回路的雪貂在其他条件下进行了测试，结果显示在清洁条件下识别元音时没有缺陷，或者当时间上一致的元音和噪声通过 180 度空间分离时也没有缺陷。然而，当失活参与噪声中元音辨别相同的听觉皮层区域时，这些动物的声音定位能力受损。我们的结果表明，作为一个对声音的空间和非空间特征表现出混合选择性的脑区，初级听觉皮层有助于多种形式的听觉。初级听觉皮层中的神经元通常对声音的位置和身份敏感。在这里，我们使用冷却或光遗传学在空间和非空间听力任务期间失活听觉皮层。听觉皮层失活损害了多种行为，证明了其在声音位置和身份分析中的作用，并证实了在神经活动中观察到的混合选择性的功能贡献。在另外两只未经训练的雪貂中进行的平行光遗传学实验通过证明表达 Channelrhodopsin-2 允许在麻醉下记录的听觉皮层活动的快速光驱动抑制，将行为与生理学联系起来。
