While small, the hypothalamus – a complex structure located deep in the brain – plays a gargantuan role in coordinating the wide array of neuronal signals that are responsible for keeping the body in a stable state. In a Special Issue of Science, authors across four Reviews unpack this key brain region's impact on physiological and behavioral homeostasis.
The hypothalamus consists of a complex collection of neural circuits. These circuits receive, process, and integrate sensory inputs to drive coordinated communication via a range of behavioral, autonomic, and endocrine pathways. These pathways support basic life functions, including regulating body temperature, hunger and thirst, mood, sex drive, heart rate, and sleep. In one Review in this issue, Harmony Fong and colleagues review the recent research that has elucidated the structural and functional complexity of hypothalamus. According to Fong et al., unlike other brain regions like the neocortex, which mediate complex functions across a relatively small number of neuronal fates, the hypothalamus is characterized by a far more complex cytoarchitecture comprised of potentially thousands of distinct cell types that form redundant, yet functionally discrete circuits. Recent advances in new methodologies, including single-cell RNA sequencing studies and modern photonic tools, have enabled high-resolution mapping of the hypothalamus' complex circuitry. Deciphering these circuits is critical to understanding physiological homeostasis and behaviors, as well as the origin of many disease states. In another Review, Long Mei and colleagues discuss how the hypothalamus controls innate social behaviors. Mei et al. highlight the role of the reproductive behavior control column (RBCC) – a group of heavily connected neural circuits that are essential for all social behaviors, including sexual, parental, and aggressive behaviors. Here, the authors summarize recent progress in understanding how the RBCC integrates diverse hormonal, metabolic, and neurotransmitter signals to sustain social interactions that ensure reproductive success.
A third Review by Antoine Adamantidis and Luis de Lecea highlights the hypothalamus' role in sleep, specifically the sleep neurons of the region that modulate control over opposing behaviors such as thermoregulation or goal-orientated behaviors during wakefulness. According to the authors, the neural substrates of wakefulness, rapid eye movement (REM) sleep, and non-REM sleep in the hypothalamus overlap both anatomically and functionally with cellular networks that support physiological and behavioral homeostasis. Finally, in the fourth Review, Garret Stuber describes what is known about the neural circuits that drive motivation. The nervous system coordinates various motivated behaviors that promote survival and evolutionary fitness, like eating and drinking and fight-or-flight responses. Although the behaviors that underly these actions are diverse, some features shared by all suggest common brain substrates are required for a range of motivational behaviors. Here, Stuber describes a framework that is useful for understanding these dynamics.
