The hypothalamus represents less than 1% of adult human brain weight, yet it integrity is absolutely critical to maintain life. The hypothalamus integrates and coordinates autonomic, endocrine, and behavioral responses necessary to maintain energy metabolism, fluid and electrolyte balance, wake-sleep cycles, thermoregulation, reproduction, and response to external threat. The last decade has seen considerable advancement in our understanding of how the hypothalamus receives visual, somatosensory, olfactory, and visceral sensory afferents necessary to perform this mission. While the broad outlines of the endocrine and autonomic control systems in the hypothalamus were demonstrated in the 1970's and 1980's, recent studies suggest that different components of the hypothalamus may generate specific patterns of response. For example, specific and quite different components of the hypothalamic-autonomic control system are activated during a fever response and by elevated leptin levels in the blood. The similarity of the chemical neuroanatomy of these control systems in the human brain, compared to rat brains, suggests that these regulatory systems have been highly conserved across mammalian evolution.

Finally, recent studies have begun to elucidate how the hypothalamus may control certain behaviors. For example, in both rodents and humans, the lateral hypothalamus contains intertwined populations of neurons that express melanin-concentrating hormone (MCH) and orexin. These neurons project to many of the same brain sites and share many response properties (e.g., expression of both peptides is regulated by leptin and fasting and both types of cells respond to glucose), but have very different physiological roles. Genetic mutations in the orexin gene or its receptors produces the phenotype of narcolepsy in both animals and in humans. Most humans with narcolepsy have degeneration of this cell population (without affecting the interspersed MCH neurons) during the second or third decade of life. Narcoleptic humans and animals eat a bit less than normals, but have slightly higher body weight (which may be due to decreased levels of overall activity). Mutations in the MCH gene, however, reduce feeding and body weight, but do not have major effects on sleep. Thus the orexin system is now thought to maintain arousal, particularly the increased activity levels during food restriction that are necessary to seek out new food sources. The interplay of the regulatory systems in the hypothalamus are complex, and will provide a number of new targets for therapeutic intervention in the next decade.