University of California, Berkeley scientists report they have mapped a neural circuit in mice that connects deep, non-REM sleep to growth hormone release and describes a feedback loop in which rising growth hormone levels influence brain arousal systems.
Researchers at the University of California, Berkeley say they have identified a brain circuit that helps explain why deep sleep is closely tied to the release of growth hormone, a key regulator of growth and metabolism.
The team reported in Cell that nerve cells in the hypothalamus coordinate growth hormone output across sleep and wake states. According to the researchers, growth hormone–releasing hormone (GHRH) neurons promote growth hormone release, while two populations of somatostatin neurons suppress it.
In experiments in mice, the group recorded neural activity using electrodes and stimulated hypothalamic neurons with light while monitoring downstream responses. They found that the balance of GHRH and somatostatin signaling changes with sleep stage: during REM sleep, both signals increased and were associated with greater growth hormone release, while during non-REM sleep somatostatin activity fell as GHRH rose more moderately.
The study also describes a feedback mechanism involving the locus coeruleus, a brainstem region known for its role in alertness and attention. As growth hormone builds up during sleep, it activates locus coeruleus neurons and can promote wakefulness; however, the researchers report that if locus coeruleus activity becomes too high, it can begin to promote sleepiness.
“Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness,” said Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author.
First author Xinlu Ding, a postdoctoral fellow in UC Berkeley’s Department of Neuroscience and the Helen Wills Neuroscience Institute, said the work provides a circuit-level framework that could guide future research into treatments aimed at restoring growth hormone balance or improving sleep. The researchers noted that such approaches may eventually be relevant to sleep disorders and diseases tied to metabolism and brain function, including diabetes and neurodegenerative conditions such as Alzheimer’s and Parkinson’s.
The research was conducted in the laboratory of Yang Dan, a UC Berkeley professor of neuroscience and of molecular and cell biology. The work was supported by the Howard Hughes Medical Institute and additional UC Berkeley funding, according to the university’s research summary.
