Catecholamine neurones in rats modulate sleep, breathing, central chemoreception and breathing variability

Brainstem catecholamine (CA) neurones have wide projections and an arousal-state-dependent activity pattern. They are thought to modulate the processing of sensory information and also participate in the control of breathing. Mice with lethal genetic defects that include CA neurones have abnormal respiratory control at birth. Also the A6 region (locus coeruleus), which contains CA neurones sensitive to CO(2)in vitro, is one of many putative central chemoreceptor sites. We studied the role of CA neurones in the control of breathing during sleep and wakefulness by specifically lesioning them with antidopamine beta-hydroxylase-saporin (DBH-SAP) injected via the 4th ventricle. After 3 weeks there was a 73-84% loss of A5, A6 and A7 tyrosine hydroxylase (TH) immunoreactive (ir) neurones along with 56-60% loss of C1 and C2 phenyl ethanolamine-N-methyltransferase (PNMT)-ir neurones. Over the 3 weeks, breathing frequency decreased significantly during air and 3 or 7% CO2 breathing in both wakefulness and non-REM (NREM) sleep. The rats spent significantly less time awake and more time in NREM sleep. REM sleep time was unaffected. The ventilatory response to 7% CO2 was reduced significantly in wakefulness at 7, 14 and 21 days (-28%) and in NREM sleep at 14 and 21 days (-26%). Breathing variability increased in REM sleep but not in wakefulness or NREM sleep. We conclude that CA neurones (1) promote wakefulness, (2) participate in central respiratory chemoreception, (3) stimulate breathing frequency, and (4) minimize breathing variability in REM sleep.