Cholinergic modulation of respiratory brain-stem neurons and its function in sleep-wake state determination.

1. Shifts in behavioural state are controlled by reciprocal changes in discharge of cholinergic and aminergic groups of brain-stem/pontine neurons. During rapid eye movement (REM) sleep, cholinergic neurons are most active and aminergic neurons are least active. 2. Significant changes occur in the central control of breathing during REM sleep; respiration rate increases in frequency and variability, brain-stem respiratory neuron discharge is generally enhanced and the outputs of some respiratory motor neuron pools are depressed. 3. Hypoglossal motor neurons (HM) control tongue movement and their depression during REM sleep has been implicated in obstructive sleep apnoea. The cellular basis of HM depression has been investigated in vitro and may be due to enhanced activation of cholinergic receptors or decreased activation of aminergic receptors. 4. In vitro preparations that show respiratory rhythmogenesis possess advantages for the investigation of the neurochemical basis of state-dependent changes in respiration. Cholinergic changes in respiratory modulation of HM recorded in rhythmic brain-stem slices from mice depend on the site of activation of cholinergic receptors.