The Mouse Primary Visual Cortex Is a Site of Production and Sensitivity to Estrogens

Kaiping Burrows,Raphael Pinaud,Liisa A Tremere,Jin-Kwon Jeong,Immo A Hansen,Ania K Majewska

doi:10.1371/journal.pone.0020400

Kaiping Burrows, Raphael Pinaud + Show 4 more

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https://doi.org/10.1371/journal.pone.0020400

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Abstract

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.

Highlights

The classic female hormone 17b-estradiol (E2), has traditionally been thought of as a steroid hormone secreted by the gonads to implement reproduction-associated behaviors through the binding to intracellular estrogen receptors that, when activated, act as transcriptional regulators and, modulate gene expression
To determine whether estrogen-associated circuits may influence visual processing, we first assessed whether the cellular components required for estrogen production and sensitivity are available in the visual cortex, in the mouse V1
We investigated whether the previously shown relationship between E2 levels and visual function may have an underlying neural basis that is analogous to our earlier findings in the auditory forebrain – namely, the presence of robust estrogen-associated networks embedded within V1 circuitry

Summary

Introduction

The classic female hormone 17b-estradiol (E2), has traditionally been thought of as a steroid hormone secreted by the gonads to implement reproduction-associated behaviors through the binding to intracellular estrogen receptors that, when activated, act as transcriptional regulators and, modulate gene expression. It has been clear for decades that estrogen signaling is significantly more ubiquitous and far reaching. Post-menopausal women subjected to estrogen replacement therapy perform better on visual memory tasks than untreated women, suggesting that E2 levels may directly affect visual function [15]

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