Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts, USA.
Eur J Neurosci. 2021 Nov;54(9):7072-7091. doi: 10.1111/ejn.15463. Epub 2021 Oct 7.
Estrogens support major brain functions including cognition, reproduction, neuroprotection and sensory processing. Neuroestrogens are synthesized within some brain areas by the enzyme aromatase and can rapidly modulate local circuit functions, yet the cellular physiology and sensory-response profiles of aromatase neurons are essentially unknown. In songbirds, social and acoustic stimuli drive neuroestrogen elevations in the auditory forebrain caudomedial nidopallium (NCM). In both males and females, neuroestrogens rapidly enhance NCM auditory processing and auditory learning. Estrogen-producing neurons in NCM may therefore exhibit distinguishing profiles for sensory-activation and intrinsic electrophysiology. Here, we explored these questions using both immunocyctochemistry and electrophysiological recordings. Immunoreactivity for aromatase and the immediate early gene EGR1, a marker of activity and plasticity, were quantified in NCM of song-exposed animals versus silence-exposed controls. Using whole-cell patch clamp recordings from NCM slices, we also documented the intrinsic excitability profiles of aromatase-positive and aromatase-negative neurons. We observed that a subset of aromatase neurons were significantly activated during song playback, in both males and females, and in both hemispheres. A comparable population of non-aromatase-expressing neurons were also similarly driven by song stimulation. Membrane properties (i.e., resting membrane potential, rheobase, input resistance and multiple action potential parameters) were similarly indistinguishable between NCM aromatase and non-aromatase neurons. Together, these findings demonstrate that aromatase and non-aromatase neurons in NCM are indistinct in terms of their intrinsic electrophysiology and responses to song. Nevertheless, such similarities in response properties may belie more subtle differences in underlying conductances and/or computational roles that may be crucial to their function.
雌激素支持包括认知、生殖、神经保护和感觉处理在内的大脑主要功能。神经雌激素由芳香酶在一些大脑区域合成，可以快速调节局部回路功能，但芳香酶神经元的细胞生理学和感觉反应特征基本上是未知的。在鸣禽中，社会和声学刺激驱动听觉前脑尾侧中隔核（NCM）中的神经雌激素升高。在雄性和雌性中，神经雌激素可快速增强 NCM 的听觉处理和听觉学习能力。因此，NCM 中的雌激素产生神经元可能表现出区分感觉激活和内在电生理的特征。在这里，我们使用免疫细胞化学和电生理记录来探索这些问题。在暴露于歌曲的动物与未暴露于歌曲的对照动物的 NCM 中，定量了芳香酶和即时早期基因 EGR1（活性和可塑性的标志物）的免疫反应性。使用来自 NCM 切片的全细胞膜片钳记录，我们还记录了芳香酶阳性和芳香酶阴性神经元的内在兴奋性特征。我们观察到，在雄性和雌性以及两个半球中，在歌曲播放期间，一组芳香酶神经元会被显著激活。同样，一组非芳香酶表达神经元也会被歌曲刺激以类似的方式驱动。NCM 芳香酶和非芳香酶神经元的膜特性（即静息膜电位、电流密度、输入电阻和多个动作电位参数）之间也没有明显差异。总之，这些发现表明，NCM 中的芳香酶和非芳香酶神经元在内在电生理学和对歌曲的反应方面没有区别。然而，这种反应特性的相似性可能掩盖了潜在电导和/或计算作用的更细微差异，这些差异可能对它们的功能至关重要。
