Trained in chemistry and cell biology, and following post-doctoral work in the new field of “neuroscience,” I became a junior faculty member in the laboratory of Neal Miller at The Rockefeller University in 1966 and was inspired by his integrative view of brain–body interactions and his pioneering work in defining the field of behavioral medicine. Together with my interest in hormone action on gene expression and the fact that very little was known about how and where hormones act in the brain, this led to a serendipitous discovery. In 1968, I discovered that the stress hormone, cortisol, secreted by our adrenal glands, is taken up from the blood and binds to receptors in the brain region known as the hippocampus. We now know that cortisol regulates gene expression and other cellular processes related to cognitive function and mood, acting in the hippocampus as well as elsewhere in the brain by epigenetic mechanisms. Epigenetics is the emerging science of how genes are seamlessly regulated by the environment, and it plays an important role in the emerging collaborations between the social and biological sciences. Here is the story of how this all happened.

What Is This Discovery?

The discovery: that stress hormones affect a brain region that we now know is involved in episodic, spatial, and contextual memory and mood regulation, rather than just affecting the hypothalamus and vegetative functions such as hunger, thirst, and sex. This discovery has triggered many studies on rats and mice, with increasing translation to human stress-related disorders, such as depression and anxiety, accelerated aging, and Alzheimer's disease. We discovered that the effects of acute and chronic stress involve not brain damage, but, rather, a remodeling of neural architecture – turnover of synaptic connections, shrinkage and growth of dendrites, and the suppression of neurogenesis (i.e., the generation of new neurons in the dentate gyrus of the hippocampus). This discovery has also engendered a broader view of brain–body interactions that has led me and colleagues to develop the concepts of allostasis and allostatic load and overload (i.e., how the body as well as the brain can be altered by too much stress so as to cause disease, as explained further below).