Sleep Physiology: Neuroanatomy and Neurochemistry

What are the brain nuclei?

small clusters of neurons in the brain, each nucleus has neurons that work together to do a specific job (mini control center), Ex. suprachiasmatic nucleus (SCN) helps control your biological clock.

What are neurotransmitters?

a chemical messenger that neurons use to communicate with each other. A neuron releases neurotransmitters into the gap between neurons (synapses) to send a signal, and they bind receptors on the next neuron to pass along the message.

What controls wakefulness?

involves several key brain nuclei that work together to maintain an alert and conscious state.

What do wake promoting neurons release?

different neurotransmitters, which promote wakefulness by stimulating the cerebral cortex and other brain regions.

What is the Ascending Reticular Activating System (ARAS)?

a network that includes various neuronal types in different brain regions and key neurotransmitter pathway.

What is the function of the ARAS?

-arousal and wakefulness- maintaining behavioral arousal, wakefulness, and attention

-filtering information- determines which sensory information is important enough to reach conscious awareness

-sleep-wake regulation- contributes to the regulation of the sleep-wake cycle

What is the region the brainstem responsible for?

the ARAS originates in the reticular formation of the brainstem.

What is the region thalamic relays responsible for?

ARAS sends signals to the thalamus which acts as a relay center for sensory information. This ensures that sensory input reaches the cerebral cortex to maintain wakefulness.

What is the region of cortical connections responsible for?

ARAS sends signals directly to the cortex and indirectly to the cortex through thalamic relays.

What are other regions of the brain responsible for?

ARAS also includes nuclei in the hypothalamus and the basal forebrain that are involved in the regulation of wakefulness.

What are aminergic pathways?

consist of brainstem nuclei that primarily use monoamines as neurotransmitters. These pathways project widely to the forebrain via the hypothalamus.

What is the noradrenergic system?

(Aminergic) Location: locus coeruleus (pons (dorsal)). Neurotransmitter: norepinephrine. Function: to promote wakefulness and alertness. Active during wakefulness and NREM sleep, and its activity decreases during REM sleep. High levels of norepinephrine are associated with increased arousal and attentiveness.

What is the serotonergic system?

(Aminergic) Location: raphe nuclei (midbrain/upper pons). Neurotransmitter: serotonin (5-HT). Function: serotonin levels are high during wakefulness and NREM sleep and decrease during REM sleep. It modulates the transition between sleep stages.

What is the histaminergic system?

(Aminergic) Location: tuberomammillary nucleus (posterior hypothalamus). Neurotransmitter: histamine. Function: promotes wakefulness and supports alertness. Histamine activity is high during wakefulness and decreases during sleep, particularly during REM sleep.

What is the dopaminergic system?

(Aminergic) Location: ventral tegmental area (midbrain). Neurotransmitter: dopamine. Function: involved in promoting arousal and maintaining wakefulness by increasing motivation and cognitive alertness.

What are cholinergic pathways?

dorsal pathways used for acetylcholine. These pathways project to the thalamus.

What is the cholinergic system?

Location: PPT and LDT (in the midbrain and pons). Neurotransmitter: acetylcholine. Function: high cholinergic tone is a hallmark of both wake and REM, supporting cortical activation in both states. Promotes EEG desynchrony typical of wakefulness. Also promotes EEG desynchrony in REM sleep.

What is the balance between the aminergic and cholinergic balance?

the ARAS relies on dynamic balance between aminergic and cholinergic activity to shift between wake, NREM, and REM states. This balance is essential for maintaining the proper transitions between different sleep stages and wakefulness.

What are the ARAS Pathways and Neurotransmitters?

Nuclei: parabrachial nucleus (PBN). Location: Pons. Neurotransmitter: glutamate. Function- promotes wakefulness by sending excitatory signals to the hypothalamus, basal forebrain, and cortex, and modulates arousal in response to external stimuli, such as threats. Connections: communicates with the hypothalamus, amygdala, and cortex, contributing to the regulation of alertness and sensory processing.

What are the orexin (hypocretin) neurons?

Location: lateral hypothalamus. Neurotransmitter: orexin (hypocretin; Hcrt). Function: stabilize wakefulness by exciting other wake-promoting systems, also helps prevent inappropriate transitions into sleep, especially during times of high arousal. Connections: send widespread projections throughout the brain.

What are the sleep promoting neurons?

Specialized cells that actively induce sleep by inhibiting wake-promoting systems and promoting the transition to and maintenance of sleep. These neurons are located in various brain regions and release inhibitory neurotransmitters such as GABA which help reduce brain activity and promote sleep state, particularly NREM sleep.

What is the Ventrolateral preoptic area (VLPO)?

Location: hypothalamus. Neurotransmitter: GABA (gamma-aminobutyric acid) and galanin. Function: primary sleep-promoting region in the brain, VLPO neurons inhibit wake-promoting neurons in the hypothalamus and brainstem (such as the orexin, histaminergic, and noradrenergic neurons). Connections: inhibitory projections to the wake-promoting systems (e.g., LC, TMN, raphe nuclei, and orexin neurons)

What is the median preoptic nucleues (MnPO)?

Location: hypothalamus. Neurotransmitter: GABA and galanin. Function: works alongside the VLPO in promoting sleep, particularly by contributing to homeostatic sleep drive. Activates before the VLPO and reinforces the VLPO activity. Connections: inhibitory projections to the arousal systems (e.g., brainstem nuclei involved in wake, orexin neurons.)

What do the VLPO and MnPO neurons do?

Co-release galanin and GABA. Inhibit wake-promoting nuclei (ARAS)- locus coeruleus (noradrenaline), raphe nuclei (serotonin), tuberomammillary nucleus (histamine), LDT/PPT (acetylcholine), orexin neurons in the lateral hypothalamus. Become active during NREM sleep, suppress cortical activation and promote NREM sleep onset and maintenance.

What is the sublateral dorsal region (SLD)?

Location: Pons. Neurotransmitter: glutamate. Function: almost exclusively fire during REM sleep. Helps initiate REM sleep, particularly important for generating atonia during REM. Connections: activates inhibitory pathways that suppress motor activity through connections to the ventromedial medulla which in turn inhibits neurons in the spinal cord.

What is the parabrachial pontine central (PBc)?

Location: pons. Neurotransmitter: glutamate. Function: play crucial role in regulation of REM by activating forebrain pathways that produce characteristic REM EEG patterns and help switch from NREM to REM. Also excite neurons (SLD) which activate REM-specific motor atonia circuits. Connections: send excitatory signal to the forebrain.

What are orexin (hypocretin) neurons?

Location: lateral hypothalamus. Neurotransmitter: orexin (hypocretin: Hcrt). Function: stabilize wakefulness by exciting other wake-promoting systems, also helps prevent inappropriate transitions into sleep, especially during times of high arousal. Connections: send widespread projections throughout the brain.

How does the sleep-wake switch operate?

through a dynamic balance between wake-promoting and sleep-promoting systems. When it favors wakefulness, wake-promoting systems are activated, and sleep-promoting systems are inhibited. When it favors sleep, the sleep-promoting systems become active, inhibiting the wake-promoting systems.

What stabilizes the sleep-wake switch?

orexin, by exciting wake-promoting neurons and preventing inappropriate transitions into sleep.

What are REM-On and REM-Off neurons?

specialized groups of neurons involved in regulating the transition into and out of REM sleep. Help control the timing, duration, and regulation of REM sleep by influencing the activity of other brain regions involved in sleep-wake regulation. Ensures proper sleep aritecture.

What happens if REM-off neurons are on?

REM sleep cannot happen.

What happens if REM-off neurons are off?

REM-on neurons can fire, and REM begins.

What happens if REM-on neurons are on?

REM sleep happens.

What happens if REM-on neurons are off?

REM sleep stops.

What are the characteristics of REM sleep?

rapid eye movements and muscle atonia. Desynchronized (low-voltage, mixed frequency, EEG). Sawtooth waves- distinctive EEG waveform seen during REM sleep, especially just before or during bursts of rapid eye movements.. Theta activity. Slow alpha activity. PGO waves.

Where are ponto-geniculo-occipital (PGO) waves?

Pons (brainstem), lateral geniculate nucleus (thalamus), occipital lobe (cerebrum)

When do PGO waves occur?

appear just before and during REM sleep, which is the stage of sleep when dream is most vivid. Closely linked to the rapid eye movements that define REM.

What is the function of PGO waves?

to play a role in generating visual imagery during dreams. May also play a role in the consolidation of memory during sleep, particularly in integrating emotional or visual memories.

Where do PGO waves propagate?

generated in the pons, move to the lateral geniculate nucleus (LGN) of the thalamus which is involved in visual processing, then move to the occipital cortex, a brain region that controls visual perception.

What is sleep-promoting adenosine?

A neuromodulator formed from the breakdown of adenosine triphosphate (ATP) during neuronal and glial energy use. Concentrations gradually rise in the brain while awake and fall during sleep.

What are the key brain regions of sleep-promoting adenosine?

adenosine especially accumulates in the basal forebrain and preoptic area, adenosine inhibits wake-promoting cholinergic neurons in the basal forebrain. It excited sleep-active neurons in the ventrolateral preoptic nucleus (VLPO), tipping the balance toward NREM sleep.

How does adenosine increase during waking?

as the brain stays awake and is metabolically active, ATP is used --> adenosine builds up. High adenosine= high sleep pressure. When you finally sleep, adenosine levels drop again.

How does caffeine promote alertness?

by blocking adenosine receptors.