Abstract
Sleep is not simply a time when the brain “switches off”. It is an active, carefully regulated process that allows the body and brain to recover, organise memories, and maintain health. This review introduces the main biological systems that control sleep, including brain regions, neurotransmitters, and hormones. It also explains how sleep changes from infancy to adulthood, how the brain clears waste during sleep, and why understanding these processes matters in medicine. Clinical and paediatric examples are used to show how sleep science connects to practice in healthcare.

1. Introduction
Sleep is a basic biological need. Every complex organism studied to date shows some form of sleep or rest pattern, suggesting it has deep evolutionary roots. In humans, sleep supports learning, mood regulation, and physical recovery. Problems with sleep are linked to a wide range of disorders — from depression and anxiety to cardiovascular disease and diabetes.

In clinical medicine, especially neurology, psychiatry, and paediatrics, understanding how sleep works helps practitioners interpret sleep studies, recognise disorders such as insomnia or narcolepsy, and tailor treatment. In this review, we will explore how the brain and body create and maintain sleep, how these processes change through life, and what this means for health professionals.

2. Neurophysiological Mechanisms of Sleep
2.1 Sleep Stages
Human sleep alternates between two main types: non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Together, these make up a full sleep cycle, which lasts about 90 minutes and repeats several times each night.

NREM sleep includes lighter stages (when we can wake up easily) and deeper stages (when brain activity slows into large “delta” waves). During this time, the body repairs tissue, releases growth hormone, and builds up immune defences. REM sleep, in contrast, is when most dreaming occurs. The brain becomes active again, but the muscles are paralysed — a mechanism that stops us from acting out our dreams.

2.2 Brain Structures and Chemical Messengers
Sleep and wakefulness are balanced by specific brain circuits and chemicals called neurotransmitters.

• The hypothalamus, a small structure deep in the brain, acts like a control centre. It uses neurons that release GABA, an inhibitory chemical, to promote sleep.

• The brainstem and basal forebrain send activating signals using chemicals such as acetylcholine, serotonin, noradrenaline, and histamine, which help keep us awake and alert.

• The orexin system, found in the hypothalamus, helps stabilise the switch between sleeping and waking.

When the balance shifts towards GABA and other inhibitory signals, the brain enters sleep. When activating systems regain control, we wake up. This “flip-flop” switch model explains why we tend to fall asleep or wake quite suddenly rather than drift in between.

Clinical example: In narcolepsy, the neurons that produce orexin are damaged or missing. Without orexin, the brain has trouble maintaining stable wakefulness, leading to sudden “sleep attacks” and episodes of muscle weakness called cataplexy.

3. Sleep Across Development — From Babies to Adults
Sleep changes as we grow. Newborn babies sleep up to 16–18 hours a day, but their sleep is split into many short periods rather than one long stretch. About half of an infant’s sleep is spent in REM (also called active sleep in babies), which supports rapid brain growth and connection-building between neurons.

During the first few months, infants begin to develop a circadian rhythm — the natural 24-hour body clock that tells us when to sleep and wake. This rhythm depends on light exposure and hormone cycles, particularly melatonin, which is released in the evening to promote sleep. In babies, melatonin production starts to stabilise around 2–3 months of age.

As children grow, deep NREM sleep becomes more dominant. In adolescence, however, the clock shifts later, making teenagers naturally inclined to stay up late and sleep in. This biological shift, combined with school start times and screen use, often leads to chronic sleep deprivation.

Paediatric case example: A preterm infant in a neonatal intensive care unit (NICU) experiences bright lights and noise day and night. These environmental disruptions can fragment sleep and interfere with brain maturation. Studies show that controlling light and noise in NICUs helps babies develop stronger sleep–wake rhythms and may improve long-term cognitive outcomes.

Understanding how sleep patterns develop helps clinicians and parents support healthy routines, identify abnormal sleep behaviour, and recognise when intervention is needed.

4. The Brain’s Cleaning System: The Glymphatic Pathway
For many years, scientists wondered how the brain removes waste, since it lacks the traditional lymphatic system found in other organs. In the past decade, researchers have discovered a network called the glymphatic system. During sleep — especially deep NREM sleep — channels around blood vessels expand, allowing cerebrospinal fluid (CSF) to wash through brain tissue and clear out waste products like amyloid-beta and tau proteins, which are linked to Alzheimer’s disease.

This system is far more active during sleep than wakefulness. In animal studies, glymphatic activity increases by up to 90% during deep sleep. In humans, imaging techniques suggest similar processes occur, though the exact mechanisms are still being studied.

In infants, the glymphatic system appears to mature alongside the development of sleep architecture. Disrupted or poor-quality sleep early in life might therefore affect how efficiently the brain can clear metabolic waste — though more research is needed to confirm this.

Clinically, this discovery may help explain why chronic sleep deprivation is associated with cognitive decline and neurodegenerative disease. It also highlights why improving deep sleep — through better sleep hygiene or specific therapies — could protect brain health over time.

5. Hormones, Sleep, and Health
Sleep interacts with many hormonal systems in the body. For example:

• Growth hormone is released mainly during deep sleep, supporting tissue repair and growth — particularly important in children.

• Cortisol, a stress hormone, normally drops at night and rises in the morning to help us wake up. Chronic sleep loss can disrupt this pattern, contributing to anxiety, metabolic changes, and immune dysfunction.

• Melatonin, produced by the pineal gland, signals the body that it’s time to sleep. Light exposure, especially from screens, can suppress melatonin and delay sleep onset.

Adolescent case example: A 15-year-old student who spends several hours on their phone each night reports difficulty sleeping and low mood. Light from the screen delays melatonin release and pushes their natural sleep time later. By reducing evening screen exposure, adding a regular bedtime, and using morning daylight, their sleep pattern and mood improve within weeks.

Understanding these hormonal interactions helps clinicians tailor advice and treatment. For instance, melatonin supplements can assist in regulating sleep cycles in some adolescents and in children with conditions like autism spectrum disorder (ASD), where circadian rhythms are often disrupted.

6. Why Understanding Sleep Neurobiology Matters in Practice
Modern sleep medicine bridges neuroscience, physiology, and clinical care. Knowing how sleep is structured helps clinicians interpret polysomnography (the overnight sleep study that records brain waves, muscle activity, and breathing). Recognising which part of the sleep process has gone wrong — for example, too little deep sleep, missing REM cycles, or irregular circadian rhythms — directs more effective treatment.

Advances in technology, including wearable sleep trackers and EEG-based home monitors, are helping researchers and clinicians measure sleep patterns in real time. However, these devices must be interpreted carefully, as they estimate rather than directly measure brain activity.

On the treatment side, drugs such as orexin receptor antagonists can now target specific arousal systems to improve insomnia. Non-drug therapies — like cognitive behavioural therapy for insomnia (CBT-I), light therapy, and environmental adjustments — remain first-line options for most patients.

In neonatal and paediatric care, clinicians can apply sleep science by:

• Using dim lighting and reduced noise in hospital settings.

• Encouraging consistent bedtime routines to strengthen circadian rhythms.

• Considering how illness, medication, and pain affect sleep cycles.

7. Future Directions
Sleep research is rapidly evolving. New imaging tools are allowing scientists to see how sleep affects the flow of CSF in the brain, how individual neurons behave during dreams, and how genetics influence sleep duration and resilience to sleep loss.

Future therapies may include targeted brain stimulation to enhance deep sleep, personalised chronotherapy to align treatment with a person’s internal body clock, and AI-based sleep analysis to detect disorders earlier.

For students and clinicians, keeping up with these discoveries is vital. Sleep touches nearly every system in the body, and understanding it better may open new ways to prevent disease, enhance mental health, and support recovery after illness.

8. Conclusion
Sleep is one of the most important yet least appreciated biological processes. It is governed by a delicate balance of brain circuits, hormones, and environmental cues that work together to protect and repair the body. From the newborn developing basic sleep rhythms to the adult maintaining cognitive performance, healthy sleep underpins lifelong wellbeing.

For early-career clinicians and biomedical students, mastering the fundamentals of sleep neurobiology provides a foundation for understanding many aspects of medicine — from growth and metabolism to emotion and memory. As technology advances, our ability to study and improve sleep will continue to grow, making it a key area for future innovation in health science.