How do glutaminergic and aminergic neurons contribute to breathing rhythm during sleep?

Glutamatergic and Aminergic Neurons in Breathing Rhythm During Sleep

Glutamatergic and aminergic neurons play critical complementary roles in respiratory rhythm regulation during sleep, with glutamatergic neurons maintaining respiratory drive while aminergic neurons modulate state-dependent changes in breathing patterns.

Neurochemical Balance During Sleep States

• During NREM sleep, both glutamatergic and aminergic neurons maintain respiratory rhythm, with intercostal muscles showing phasic and tonic activity that stabilizes the compliant chest wall 1.
• During REM sleep, aminergic neurons (serotonergic and noradrenergic) significantly decrease their activity while cholinergic neurons increase their firing, creating a neurochemical shift that affects breathing patterns 2.
• The pedunculopontine tegmentum (PPT) contains cholinergic neurons crucial for both wakefulness and REM sleep regulation, with connections to the hypothalamus that influence respiratory control 3.

Aminergic Neuron Function

• Aminergic neurons from the raphe nuclei (serotonergic) and locus coeruleus (noradrenergic) are most active during wakefulness and least active during REM sleep 2, 4.
• When aminergic activity decreases during REM sleep, there is inhibition of intercostal muscles, leading to chest wall distortion during inspiration 1.
• The decreased aminergic activity during REM sleep contributes to the characteristic increased frequency and variability in respiration rate observed during this sleep stage 2.

Glutamatergic Neuron Function

• Glutamatergic neurons in the central pattern generator (CPG) located in the ventral respiratory group (VRG) of the brainstem are primarily responsible for generating the basic respiratory rhythm 5.
• During sleep transitions, glutamatergic pathways maintain essential respiratory drive while being modulated by state-dependent aminergic and cholinergic inputs 6.
• Glutamatergic neurons originating in the prefrontal cortex project to the striatum and influence respiratory control through cortico-striatal-thalamic-cortical circuitry 5.

Sleep Stage-Specific Respiratory Changes

• In NREM sleep, phasic and tonic activity of intercostal muscles help stabilize the chest wall, with no abdominal muscle activation in healthy individuals 1.
• During REM sleep, intercostal muscles are inhibited due to decreased aminergic activity, leading to potential chest wall distortion 1.
• REM-specific neurons in the gigantocellular and lateral medullary tegmental fields begin rhythmically discharging at REM sleep onset, with discharge rates highly correlated with respiratory frequency 7.

Clinical Implications

• The balance between glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmission is crucial for maintaining normal respiratory patterns during sleep 6.
• Dysfunction in these neurochemical systems can contribute to sleep-related breathing disorders, including obstructive sleep apnea 8.
• Surface electromyography (EMG) can be used to assess respiratory muscle activation patterns during sleep, with different patterns observed between NREM and REM sleep 1.

Hypothalamic Influence

• The hypothalamus plays a key role in coordinating sleep-wake states through orexin neurons, which indirectly affect respiratory control 9.
• Orexin neurons from the lateral hypothalamus inhibit "REM-off" cells through cholinergic mechanisms, influencing respiratory patterns during REM sleep 9.
• The suprachiasmatic nuclei within the hypothalamus provide master coordination of sleep/wake rhythms, which in turn affects respiratory control 9.

Understanding these neurochemical mechanisms is essential for diagnosing and treating sleep-related breathing disorders, as they reveal how normal respiratory control can be compromised during different sleep states.