Multiscale activity imaging in the mammary gland reveals how oxytocin enables lactation

Abstract

The mammary epithelium is indispensable for the continued survival of more than 5000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate milk ejection. Using quantitative, multidimensional imaging of mammary cell ensembles, we reveal how stimulus evoked Ca2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically deform the innermost layer of luminal cells, compelling them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive displacement pumps, each linked to a contractile ductal network, milk is delivered into the mouth of the dependent neonate, seconds after the command. Significance StatementThe mammary gland is functional for only a brief period of a females lifetime--if at all. During this time, it operates not for the survival of the individual, but for the survival of her species. Here, we visualize the nature of alveolar contractions in the functionally-mature mammary gland, revealing how specialized epithelial cells, which possess the ability to behave like smooth muscle cells, undergo Ca2+-dependent contractions. We demonstrate that individual oscillators can be electrically coupled to achieve global synchrony, a phenomenon that has not yet been observed in the mammary gland. By imaging activity across scales, we provide a window into the organization, dynamics and role of epithelial Ca2+ oscillations in the organ principally responsible for sustaining neonatal life in mammals.