Defining the brain control of physiological stability

The last few decades have seen major advances in neurobiology and uncovered novel genetic and cellular substrates involved in the control of physiological set points. In this Review, I discuss the limitations in the definition of homeostatic set points established by Walter B Canon and highlight evidence that two other physiological systems, namely rheostasis and allostasis provide distinct inputs to independently modify set-point levels. Using data collected over the past decade, the hypothalamic and genetic basis of regulated changes in set-point values by rheostatic mechanisms are described. Then, the role of higher-order brain regions, such as hippocampal circuits, for experience-dependent, allostatic induced changes in set-points are outlined. I propose that these systems provide a hierarchical organization of physiological stability that exists to maintain set-point values. The hierarchical organization of physiology has direct implications for basic and medical research, and clinical practice.