Editorial: Advances in Neuroscience: The BRAIN Initiative and Implications for Neuroendocrinology

The study of neuroscience leverages contributions by members of many interdisciplinary fields, including biologists, physicians, psychologists, chemists, geneticists, computer scientists, engineers, and mathematicians, among many others. Historically a field in which progress has been challenged and slowed by the lack of available tools for the study of neurons and their connections, the scope and pace have broadened in recent years as a result of landmark advances and discoveries in molecular biology, electrophysiology, genetics, and computational neuroscience. The techniques used by neuroscientists have expanded enormously, ranging from molecular and cellular studies of individual neurons, to the use of optogenetics to control and monitor the activities of individual neurons in living tissue, to the study of neural networks and mapping of neural connections and to molecular, structural, and functional imaging of the brain with increasing resolution. These advances in technology lay the groundwork for more studies to better understand how the brain works. Underlying these studies is the motivation to translate these discoveries into new therapies for the many devastating diseases of the nervous system. These technological advances have similarly accelerated discoveries in the field of neuroendocrinology. Neuroendocrinology is the study of the interaction and interconnection between the nervous system and the endocrine system and the communication and integration between these systems to regulate diverse physiological processes throughout the body. A great number of advances made in recent years have provided substantial insights into the neuroendocrine control of reproduction, metabolism, appetite and energy homeostasis, growth and development, and the interconnections among these processes as well as the impacts of these processes on behavior and the function of other parts of the brain. The advances in neuroscience have led to a better understanding of disorders of the nervous system, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, autism, schizophrenia, and traumatic brain injury and brought us to the brink of the development of new therapies. On the heels of the success of the Human Genome Project, President Barack Obama stated in his 2013 State of the Union Address, “If we want to make the best products, we also have to invest in the best ideas. … Every dollar we invested to map the human genome returned $140 to our economy. … Today our scientists are mapping the human brain to unlock the answers to Alzheimer's. … Now is not the time to gut these job-creating investments in science and innovation. Now is the time to reach a level of research and development not seen since the height of the Space Race” (1). Shortly thereafter, in April 2013, President Obama launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative to “accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact.” The National Institutes of Health, National Science Foundation, and Defense Advanced Research Projects Agency jointly supported this initiative, and private sector partners including The Allen Institute for Brain Science, the Howard Hughes Medical Institute, the Kavli Foundation, and the Salk Institute for Biological Studies all committed substantial funds as well. Francis S. Collins, director of the National Institutes of Health, established a high-level working group to help shape this new initiative, which, after input from the scientific community, patient advocate groups, and the general public, ultimately released their report in June 2014, articulating the scientific goals and priorities of the BRAIN Initiative over a 10-year period, with an ambitious $4.5 billion price tag. The final report of the BRAIN Initiative Working Group focuses on the development and use of tools for acquiring fundamental insight about how the nervous system functions in health and disease (2). The primary focus in the first 5 years is on technology development, shifting in the second 5 years to a primary focus on integrating technologies to make fundamental new discoveries about the brain. Seven goals, or areas of high priority, were identified and articulated: 1) discovering diversity: identify and provide experimental access to the different brain cell types to determine their roles in health and disease; 2) maps at multiple scales: generate circuit diagrams that vary in resolution from synapses to the whole brain; 3) the brain in action: produce a dynamic picture of the functioning brain by developing and applying improved methods for large-scale monitoring of neural activity; 4) demonstrating causality: link brain activity to behavior with precise interventional tools that change neural circuit dynamics; 5) identifying fundamental principles: produce conceptual foundations for understanding the biological basis of mental processes through development of new theoretical and data analysis tools; 6) advancing human neuroscience: develop innovative technologies to understand the human brain and treat its disorders and create and support integrated human brain research networks; and, most importantly, 7) from BRAIN Initiative to the brain: integrate new technological and conceptual approaches produced in goals 1–6 to discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception, and action in health and disease. “The BRAIN Initiative focuses a welcome lens on the current potential for impactful advances in neuroscience and the treatment of nervous system disorders … Given its broad scope, the emphasis on analysis of circuits of interacting neurons, and the interface between structure, function, and dynamic patterns of activity, it is our hope that the important effects of hormones on these circuits and the field of neuroendocrinology will be increasingly recognized as this initiative moves forward.” The BRAIN Initiative focuses a welcome lens on the current potential for impactful advances in neuroscience and the treatment of nervous system disorders. Already new funding opportunities have been released as a result. A Multi-Council Working Group was recently established to guide future funding concepts for the BRAIN initiative. Given its broad scope, the emphasis on analysis of circuits of interacting neurons, and the interface between structure, function, and dynamic patterns of activity, it is our hope that the important effects of hormones on these circuits and the field of neuroendocrinology will be increasingly recognized as this initiative moves forward. A search of the Working Group's report for the words endocrinology, neuroendocrinology, hormone, estrogen, testosterone, sex, puberty, and gender garnered no hits; the word aging was present only twice. Given the importance of hormones on brain development and function, the Endocrine Society under President Teresa Woodruff's leadership submitted feedback and comment to the BRAIN Working Group in April 2014, in response to their interim report. In this letter, the important roles of hormones on brain development and function and the actions of hormones on human behavior were emphasized. Importantly, the Endocrine Society noted that any ambitious plan such as the BRAIN Initiative should include a consideration of sex differences as a critical biological variable essential to the understanding of both normal and pathological brain states. There are sex differences, mediated in part by sex steroid hormones, in both structure and function of the brain. Indeed, the importance of sex differences as a critical variable was recently highlighted in an editorial in Nature by Janine A. Clayton, director of the National Institutes of Health Office of Research on Women's Health, and Francis Collins (3, 4). Furthermore, brain circuitry is dynamically changing across the life span (in utero, during puberty, during pregnancy, and with aging), influenced in large part by hormonal changes that occur during these developmental phases. It is therefore critical to take hormonal status into consideration when studying brain structures, neuronal circuits, and brain function. Bidirectional hormonal signals between the brain and other organs have profound influence on metabolism and on human behavior, as has been emphasized recently, for example, in studies of signals between the gut and the brain (5). The hypothalamus plays a key role in integrating signals from the central nervous system and peripheral organs to control physiology and homeostasis in health and disease. In this regard, it is reassuring to note that mapping circuits and connections in the hypothalamus is emphasized in the report. In the current environment, given the new technologies and tools available for studies of the nervous system, the recent advances in our understanding of neurons, neural circuits, and brain structure, the recent focus and interest in deepening our understanding of the brain in health and disease, and now the new initiatives and funding opportunities, it appears that exciting times are ahead for the field of neuroscience and, we hope, neuroendocrinology.