[How does the brain wake up? The nitric oxide blow]
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Updated: Aug 8, 2026

A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
Published on: May 4, 2021
1Universidad de A Coruña, Neurocom, Departamento de Medicina, Facultad de Ciencias da Saude, Campus de Oza, E-15006 A Coruña, Spain.
Introduction:
A synthesis of the role of the neuromodulator nitric oxide (NO) on the sleep-wake cycle control is made, emphasizing the function of the activating ascending pathways implicated in arousal.
Development:
There are some hypotheses regarding the role of sleep: memory consolidation, ecological factors, cellular repair and nervous system development. The sleep-wake cycle is an active process, modulated by subcortical regions (mesopontine nuclei, diencephalon and basal forebrain) with connections and reciprocal interactions among them. NO is released by neurons and terminals of the sleep-wake cycle modulatory nuclei. The role of NO in this cycle is mainly linked to activation processes: transition to and maintenance of waking and rapid eye movement (REM) sleep. At thalamic level NO is released by cholinergic fibers of the mesopontine nuclei and induces a facilitation of neural responses. In the basal forebrain there exists NO in the cholinergic cells contacting the cortex, suggesting that this ascending pathway can also collaborate in cortical activation through the release of NO.
Conclusions:
NO has been identified in neurons of the brain areas controlling the modulation of arousal; hence, this gaseous neuromodulator can have an essential function promoting a quick and global activation of cortical neurons.
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