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The results of this Forum give reason to hope that new therapies for nervous system disorders are not only possible but also realistic. This optimism, visible in the vigorous discussions captured in this book, is grounded both in an acute understanding of the fundamental challenges that exist and the synergies that grew out of the process. Much remains to be accomplished if promising ideas, solutions, and paradigms are to be realized in academia and industry. Thus given the importance of innovative ideas and experimentation, we have no desire to reach premature closure on precise approaches to either neurodevelopmental or neurodegenerative disorders. There was, however, broad agreement that genetics and a greater emphasis on human biology offer essential springboards for effective new approaches to pathophysiology and therapies. After decades of stagnation marked, inter alia, by all too many disappointing failures in costly, late-stage clinical trials, what is the basis for our optimism? Central to this is the remarkable advent of new tools and technologies during the last decade which are truly revolutionizing our ability to study the nervous system in unprecedented ways (Hyman 2012; Pankevich et al. 2014). The resulting sense of promise that we perceive comes with the recognition that a revolution in translational neuroscience has already begun. Our use of the term “revolution” is not accidental: the participants of the Forum agreed that for brain disorders, successful discovery and development of diseasemodifying therapies require most certainly a revolution, not merely incremental progress realized through past approaches. We (the attendees and coauthors of this volume) are already participating, to a great degree, in this much needed transformation; this Forum provided valuable space to refl ect on what has happened and to discuss, and occasionally argue, about what needs to be done to accelerate progress. Those from industry made clear that they understood the high prevalence of many brain disorders, the vast unmet medical needs, and the enormous global disease burden associated with these diseases. Equally, however, they stressed that unless the new biology discussed at the Forum produced more than incremental advances, it would be diffi cult to justify signifi cant investments in brain and nervous system disorders when other areas of research (e.g., cancer) were awash in targets, had clear paths to target

How Do We Define and Modulate Circuits in Animals That Are Relevant to Pathophysiology in Humans?