Plasticity in respiratory motor control: intermittent hypoxia and hypercapnia activate opposing serotonergic and noradrenergic modulatory systems

Experimental results consistently show that the respiratory control system is plastic, such that environmental factors and experience can modify its p erformance. Such plasticity may represent basic neurobiological principles of learning and memory, whereby intermittent sensory stimulation produces l ong-term alterations (i.e. facilitation or depression) in synaptic transmis sion depending on the timing and intensity of the stimulation. In this revi ew, we propose that intermittent chemosensory stimulation produces long-ter m changes in respiratory motor output via specific neuromodulatory systems. This concept is based on recent data suggesting that intermittent hypoxia produces a net long-term facilitation of respiratory output via the seroton ergic system, whereas intermittent hypercapnia produces a net long-term dep ression by a mechanism associated with the noradrenergic system. There is s uggestive evidence that, although both respiratory stimuli activate both mo dulatory systems, the balance is different. Thus, these opposing modulatory influences on respiratory motor control may provide a 'push-pull' system, preventing unchecked and inappropriate fluctuations in ventilatory drive. ( C) 2001 Elsevier Science Inc. All rights reserved.