Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205.
Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 2023 Jul 25;120(30):e2219340120. doi: 10.1073/pnas.2219340120. Epub 2023 Jul 17.
Coordinated functioning of the two cortical hemispheres is crucial for perception. The human auditory cortex (ACx) shows functional lateralization with the left hemisphere specialized for processing speech, whereas the right analyzes spectral content. In mice, virgin females demonstrate a left-hemisphere response bias to pup vocalizations that strengthens with motherhood. However, how this lateralized function is established is unclear. We developed a widefield imaging microscope to simultaneously image both hemispheres of mice to bilaterally monitor functional responses. We found that global ACx topography is symmetrical and stereotyped. In both male and virgin female mice, the secondary auditory cortex (A2) in the left hemisphere shows larger responses than right to high-frequency tones and adult vocalizations; however, only virgin female mice show a left-hemisphere bias in A2 in response to adult pain calls. These results indicate hemispheric bias with both sex-independent and -dependent aspects. Analyzing cross-hemispheric functional correlations showed that asymmetries exist in the strength of correlations between DM-AAF and A2-AAF, while other ACx areas showed smaller differences. We found that A2 showed lower cross-hemisphere correlation than other cortical areas, consistent with the lateralized functional activation of A2. Cross-hemispheric activity correlations are lower in deaf, otoferlin knockout (OTOF) mice, indicating that the development of functional cross-hemispheric connections is experience dependent. Together, our results reveal that ACx is topographically symmetric at the macroscopic scale but that higher-order A2 shows sex-dependent and independent lateralized responses due to asymmetric intercortical functional connections. Moreover, our results suggest that sensory experience is required to establish functional cross-hemispheric connectivity.
两个大脑半球的协调运作对感知至关重要。人类听觉皮层（ACx）表现出功能偏侧化，左半球专门处理言语，而右半球分析频谱内容。在小鼠中，处女雌性对幼鼠发声表现出左半球反应偏向，随着母性的增强而增强。然而，这种偏侧化功能是如何建立的尚不清楚。我们开发了一种宽场成像显微镜，可以同时对小鼠的两个半球进行成像，以双侧监测功能反应。我们发现，全局 ACx 拓扑结构是对称和刻板的。在雄性和处女雌性小鼠中，左半球的次级听觉皮层（A2）对高频音调和成年叫声的反应比右侧更大；然而，只有处女雌性小鼠在 A2 对成年疼痛叫声的反应中表现出左半球偏向。这些结果表明，半球偏向具有性别独立和依赖的方面。分析跨半球功能相关性表明，DM-AAF 和 A2-AAF 之间的相关性强度存在不对称性，而其他 ACx 区域的差异较小。我们发现 A2 与其他皮质区域相比，跨半球相关性较低，这与 A2 的偏侧功能激活一致。失聪、otoferin 敲除（OTOF）小鼠的跨半球活动相关性较低，表明功能跨半球连接的发育依赖于经验。总之，我们的研究结果表明，ACx 在宏观尺度上具有拓扑对称性，但由于皮质间功能连接的不对称性，较高阶的 A2 表现出性别依赖和独立的偏侧化反应。此外，我们的结果表明，感觉经验是建立功能跨半球连接所必需的。
