Faculty Profile

Respiratory Neurophysiology Laboratory, Sleep Disorders Program, Division of Sleep Medicine, Brigham and Women's Hospital

Research of our laboratory is directed at understanding neural control of respiration, particularly with respect to the mechanisms underlying neural plasticity of respiratory motor control. Our current research project focuses mainly on:
1) the chronic intermittent hypoxia- and sleep fragmentation-induced plasticity in respiratory long-term facilitation (a persistent augmentation of respiratory activity following acute intermittent hypoxia), and in ventilatory chemo-reflexes to hypoxia and hypercapnia
2) the interaction and counteraction between chronic intermittent hypoxia effects and sleep disruption effects on ventilatory control
3) the cellular and neuronal mechanisms mediating these forms of ventilatory plasticity, especially those related to the serotonergic, glutamatergic and adenosinergic systems

Chronic intermittent hypoxia and sleep fragmentation are the two primary events associated with obstructive sleep apnea, a major sleep disordered breathing. Understanding how and where chronic intermittent hypoxia and sleep disruption affect the respiratory control system will enhance our knowledge of pathophysiology and treatment of obstructive sleep apnea syndrome. Recently, our research interests have also been extended to several new directions:
1) the age-related changes in the intermittent hypoxia- and sleep disruption-induced plasticity in ventilatory control
2) the intracellular mechanisms (such as phosphorylation of NMDA receptor subunit(s) on major respiratory motoneurons by certain protein kinases) that are crucial for the formation and maintenance of respiratory long-term facilitation
3) the role of respiratory long-term facilitation in the neural control of upper airway patency, as well as the potential influences of chronic intermittent hypoxia, sleep disruption, age and/or gender on this role.

Yi Zhang, PhD, 2000- 2002
Michelle T. McGuire, PhD, 2000- Present
Ying Cao, MD, PhD, 2006- Present
Chun Liu, PhD, MD, 2007– Present

Dexter F. Speck
Gordon S. Mitchell

NIH/NHLBI
"Ventilatory control after sleep fragmentation"
To study the effects of sleep fragmentation on ventilatory control, including respiratory long-term facilitation as well as ventilatory chemo-reflexes to hypoxia and hypercapnia
Role: PI

McGuire M, Tartar JL, Cao Y, McCarley RW, White DP, Strecker RE, Ling L. Sleep fragmentation impairs ventilatory long-term facilitation via adenosine A1 receptors.
J Physiol. 2008 Nov 1;586(Pt 21):5215-29. [PMID: 18787037]

McGuire M, Liu C, Cao Y, Ling L. Formation and maintenance of ventilatory long-term facilitation require NMDA but not non-NMDA receptors in awake rats.
J Appl Physiol. 2008 Sep;105(3):942-50. [PMID: 18583381]

Ling L. Serotonin and NMDA receptors in respiratory long-term facilitation.
Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):233-41. Review. [PMID:18606575]

McGuire M, Zhang Y, White DP, Ling L. Phrenic long-term facilitation requires NMDA receptors in the phrenic motonucleus in rats.
J Physiol. 2005 Sep 1;567(Pt 2):599-611. Epub 2005 Jun 2. [PMID: 15932891]

McGuire M, Ling L. Ventilatory long-term facilitation is greater in 1- vs. 2-mo-old awake rats.
J Appl Physiol. 2005 Apr;98(4):1195-201. Epub 2004 Dec 10. [PMID: 15591293] 

Zhang Y, McGuire M, White DP, Ling L. Episodic phrenic-inhibitory vagus nerve stimulation paradoxically induces phrenic long-term facilitation in rats.
J Physiol. 2003 Sep 15;551(Pt 3):981-91. Epub 2003 Jul 18. [PMID: 12872010] 

Ling L, Fuller DD, Bach KB, Kinkead R, Olson EB Jr, Mitchell GS. Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing.
J Neurosci. 2001 Jul 15;21(14):5381-8. [PMID: 11438615]