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1 Department of Comparative Biosciences, 3 Department of Neurology, 4 Department of Preventive Medicine, and 2 Center for Neuroscience, University of Wisconsin, Madison, Wisconsin 53706
Intermittent hypoxia elicits long-term facilitation (LTF), a persistent augmentation (hours) of respiratory motor output. Considerable recent progress has been made toward an understanding of the mechanisms and manifestations of this potentially important model of respiratory plasticity. LTF is elicited by intermittent but not sustained hypoxia, indicating profound pattern sensitivity in its underlying mechanism. During intermittent hypoxia, episodic spinal serotonin receptor activation initiates cell signaling events, increasing spinal protein synthesis. One associated protein is brain-derived neurotrophic factor, a neurotrophin implicated in several forms of synaptic plasticity. Our working hypothesis is that increased brain-derived neurotrophic factor enhances glutamatergic synaptic currents in phrenic motoneurons, increasing their responsiveness to bulbospinal inspiratory inputs. LTF is heterogeneous among respiratory outputs, differs among experimental preparations, and is influenced by age, gender, and genetics. Furthermore, LTF is enhanced following chronic intermittent hypoxia, indicating a degree of metaplasticity. Although the physiological relevance of LTF remains unclear, it may reflect a general mechanism whereby intermittent serotonin receptor activation elicits respiratory plasticity, adapting system performance to the ever-changing requirements of life.
respiratory control; serotonin; neurotrophins; brain-derived neurotrophic factor; episodic hypoxia
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K. F. Morris, D. M. Baekey, S. C. Nuding, T. E. Dick, R. Shannon, and B. G. Lindsey Plasticity in Respiratory Motor Control: Invited Review: Neural network plasticity in respiratory control J Appl Physiol, March 1, 2003; 94(3): 1242 - 1252. [Abstract] [Full Text] [PDF]
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H. V. Forster Plasticity in Respiratory Motor Control: Invited Review: Plasticity in the control of breathing following sensory denervation J Appl Physiol, February 1, 2003; 94(2): 784 - 794. [Abstract] [Full Text] [PDF]
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G. S. Mitchell and S. M. Johnson Plasticity in Respiratory Motor Control: Invited Review: Neuroplasticity in respiratory motor control J Appl Physiol, January 1, 2003; 94(1): 358 - 374. [Abstract] [Full Text] [PDF]
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