Neuroscience and Behavior, Center for Neuroendocrine Studies, University of Massachusetts, 639 N. Pleasant St., Amherst, MA 01003, United States.
Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, 83 Fenyang Rd, Xuhui District, Shanghai 200031, China.
Cereb Cortex. 2023 Mar 21;33(7):3401-3420. doi: 10.1093/cercor/bhac280.
Sensory neurons parse millisecond-variant sound streams like birdsong and speech with exquisite precision. The auditory pallial cortex of vocal learners like humans and songbirds contains an unconventional neuromodulatory system: neuronal expression of the estrogen synthesis enzyme aromatase. Local forebrain neuroestrogens fluctuate when songbirds hear a song, and subsequently modulate bursting, gain, and temporal coding properties of auditory neurons. However, the way neuroestrogens shape intrinsic and synaptic properties of sensory neurons remains unknown. Here, using a combination of whole-cell patch clamp electrophysiology and calcium imaging, we investigate estrogenic neuromodulation of auditory neurons in a region resembling mammalian auditory association cortex. We found that estradiol rapidly enhances the temporal precision of neuronal firing via a membrane-bound G-protein coupled receptor and that estradiol rapidly suppresses inhibitory synaptic currents while sparing excitation. Notably, the rapid suppression of intrinsic excitability by estradiol was predicted by membrane input resistance and was observed in both males and females. These findings were corroborated by analysis of in vivo electrophysiology recordings, in which local estrogen synthesis blockade caused acute disruption of the temporal correlation of song-evoked firing patterns. Therefore, on a modulatory timescale, neuroestrogens alter intrinsic cellular properties and inhibitory neurotransmitter release to regulate the temporal precision of higher-order sensory neurons.
感觉神经元以极高的精度解析毫秒级变化的声音流，如鸟鸣和言语。像人类和鸣禽这样的发声学习者的听觉大脑皮层包含一种非传统的神经调质系统：雌激素合成酶芳香酶的神经元表达。当鸣禽听到歌曲时，局部前脑神经雌激素会波动，并随后调节听觉神经元的爆发、增益和时间编码特性。然而，神经雌激素如何塑造感觉神经元的内在和突触特性尚不清楚。在这里，我们使用全细胞膜片钳电生理学和钙成像相结合的方法，研究了类似于哺乳动物听觉联合皮层的区域中听觉神经元的雌激素能调制作用。我们发现，雌二醇通过膜结合的 G 蛋白偶联受体迅速增强神经元放电的时间精度，而雌二醇迅速抑制抑制性突触电流，同时保留兴奋。值得注意的是，雌二醇对固有兴奋性的快速抑制是由膜输入电阻预测的，并且在雄性和雌性中都观察到了这种情况。体内电生理学记录的分析结果证实了这一发现，其中局部雌激素合成阻断导致歌曲诱发放电模式的时间相关性急性中断。因此，在调制时间尺度上，神经雌激素改变内在细胞特性和抑制性神经递质释放，以调节高级感觉神经元的时间精度。
