Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2011;6(5):e20400. doi: 10.1371/journal.pone.0020400. Epub 2011 May 24.
The classic female estrogen, 17β-estradiol (E2), has been repeatedly shown to affect the perceptual processing of visual cues. Although gonadal E2 has often been thought to influence these processes, the possibility that central visual processing may be modulated by brain-generated hormone has not been explored. Here we show that estrogen-associated circuits are highly prevalent in the mouse primary visual cortex (V1). Specifically, we cloned aromatase, a marker for estrogen-producing neurons, and the classic estrogen receptors (ERs) ERα and ERβ, as markers for estrogen-responsive neurons, and conducted a detailed expression analysis via in-situ hybridization. We found that both monocular and binocular V1 are highly enriched in aromatase- and ER-positive neurons, indicating that V1 is a site of production and sensitivity to estrogens. Using double-fluorescence in-situ hybridization, we reveal the neurochemical identity of estrogen-producing and -sensitive cells in V1, and demonstrate that they constitute a heterogeneous neuronal population. We further show that visual experience engages a large population of aromatase-positive neurons and, to a lesser extent, ER-expressing neurons, suggesting that E2 levels may be locally regulated by visual input in V1. Interestingly, acute episodes of visual experience do not affect the density or distribution of estrogen-associated circuits. Finally, we show that adult mice dark-reared from birth also exhibit normal distribution of aromatase and ERs throughout V1, suggesting that the implementation and maintenance of estrogen-associated circuits is independent of visual experience. Our findings demonstrate that the adult V1 is a site of production and sensitivity to estrogens, and suggest that locally-produced E2 may shape visual cortical processing.
经典的女性雌激素 17β-雌二醇(E2)已被反复证明会影响视觉线索的感知处理。尽管性腺 E2 通常被认为会影响这些过程,但中枢视觉处理是否可能受到大脑产生的激素调节尚未得到探索。在这里,我们表明雌激素相关回路在小鼠初级视觉皮层(V1)中非常普遍。具体来说,我们克隆了芳香酶,一种雌激素产生神经元的标志物,以及经典的雌激素受体(ERs)ERα和 ERβ,作为雌激素反应神经元的标志物,并通过原位杂交进行了详细的表达分析。我们发现,单眼和双眼 V1 都富含芳香酶和 ER 阳性神经元,这表明 V1 是雌激素产生和敏感的部位。使用双荧光原位杂交,我们揭示了 V1 中雌激素产生和敏感细胞的神经化学特征,并证明它们构成了一个异质的神经元群体。我们进一步表明,视觉体验会使大量芳香酶阳性神经元参与其中,而表达 ER 的神经元则参与较少,这表明 E2 水平可能在 V1 中受到视觉输入的局部调节。有趣的是,急性视觉体验不会影响雌激素相关回路的密度或分布。最后,我们还发现,从出生起就被黑暗饲养的成年小鼠在 V1 中也表现出正常的芳香酶和 ERs 分布,这表明雌激素相关回路的实施和维持与视觉体验无关。我们的研究结果表明,成年 V1 是雌激素产生和敏感的部位,并表明局部产生的 E2 可能会影响视觉皮层处理。