Richard Horner

Vice-Chair, Research, Department of Physiology
Professor, Physiology and Medicine
Canada Research Chair in Sleep and Respiratory Neurobiology
Director, Sleep and Biological Rhythms Toronto, a CIHR team research and training program
Team Lead, Integrative Program in Sleep, Sedation and Anesthetic Sciences

Research Synopsis

Keywords: Sleep / Sedation / Anesthesia / Electrocortical activity / Respiration / Motor control / GABA / K+ channels. 

Detailed Description: Sleep modifies brain activity and vital autonomic functions such as breathing. These modifications predispose individuals to sleep and breathing disorders, and a diminished ability to arouse from sleep in response to respiratory distress. Depression of brain activity and breathing also occur with commonly used prescription and non-prescription sedating agents such as hypnotics, anesthetics and opioid analgesics. Evidence now indicates that the common and serious (and at times life-threatening) problems of sleep and sedation-induced depression of brain activity, arousal responses and breathing may be working through common brain pathways acting on common cellular mechanisms. To identify these common pathways and mechanisms is the current focus of our research. Through our links to other collaborating research teams and infrastructure - via Sleep and Biological Rhythms Toronto, a CIHR Team Research and Training Program, and the Integrative Program in Sleep, Sedation and Anesthetic Sciences - we are positioned to drive and coordinate citywide translational collaborative research and educational initiatives spanning basic science to public health.

METHODS USED

Cell and tissue culture: Brain slice, neurons. 

Procedures: Adenovirus, behavioral tests, EEG, electrophysiology, immunohistochemistry, in vitro electrophysiology, in vivo electrophysiology, in vivo recording of local field potentials, micro and macrostimulation of peripheral nerves and central brain structures, signal transduction characterization, siRNA, stereotaxic brain surgery, western blot

EQUIPMENT USED

Amplifier, analytical balances, cryostat, digital microscope, electrophysiology rig, fluorescence microscope, infusion apparatus

PRESENT TRAINEES

a.         Masters and Doctoral Students:

2011-present:   Ms. Lia Mesbah-Oskui, PhD student
                                Primary supervisor                  
                                Title of thesis: Common mechanisms of sleep and the sedative components of anesthesia

2012-present:   Mr. Kevin Grace, PhD student
                                Primary supervisor                  
                                Title of thesis: Mechanisms of Arousal State Regulation and Behavior

2012-present:   Mr. Michael Vu, MSc student
                                Primary supervisor                  
                                Title of thesis: A role for TASK channels in H1 receptor-mediated activation of cholinergic neurons in the basal        forebrain: mechanisms of cortical activation in wakefulness, sleep and anesthesia

2014-present:   Mr. Garret Horton, MSc student
                                Primary supervisor                  
                                Title of thesis: Activation of a respiratory motor circuit by remote control

PRESENT COLLABORATIONS

Within the Department of Physiology

Beverley Orser, MD, PhD: Departments of Anesthesia and Physiology
Ali Salahpour, PhD: Department of Pharmacology and Toxicology
John Peever, PhD: Department of Cell & Systems Biology, and Physiology
Indra Narang, MD: Department of Pediatrics
Frances Chung, MBBS: Department of Anesthesia
T. Douglas Bradley, MD: Division of Respirology, Department of Medicine
Robyn Stremler, RN, PhD: Faculty of Nursing
Brian Murray, MD: Division of Neurology, Department of Medicine
Chris Perumalla, PhD: Department of Physiology, and Director of Division of Teaching Laboratories
Nohjin Kee, PhD: Department of Physiology
Zheng-Ping Jia PhD: Hospital for Sick Children Research Institute and Department of Physiology

Outside the Department of Physiology

Dr. Keith Wafford, PhD: Eli Lilly, UK
Dr. John Greer, PhD: Department of Physiology, University of Alberta
Dr. Doug Bayliss, PhD: University of Virginia, USA
Dr. Dan Mulkey, PhD: University of Connecticut
Dr. Kevin Wickman, PhD: University of Minnesota

Committee member/Officer of national or international scientific organization:
2011-2014: Canadian Institutes of Health Research, Member of “Respiratory System” Grants Committee.

2011-present: Canadian Institutes of Health Research, Member of Sleep and Circadian Rhythms Executive Steering Committee to oversee Canada-wide research and training programs.

Recent Publications

Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur. Grace KP, Vanstone LE, Horner RL.J Neurosci. 2014 Oct 22;34(43):14198-209.

Thalamic δ-subunit containing GABAA receptors promote electrocortical signatures of deep non-REM sleep but do not mediate the effects of etomidate at the thalamus in vivo. Mesbah-Oskui L, Orser BA, Horner RL. J Neurosci. 2014 Sep 10;34(37):12253-66.

Mechanisms of REM sleep in health and disease. Fraigne JJ, Grace KP, Horner RL, Peever J. Curr Opin Pulm Med. 2014 Nov;20(6):527-32.

Cholinergic involvement in control of REM sleep paralysis. Torontali ZA, Grace KP, Horner RL, Peever JH. J Physiol. 2014 Apr 1;592(Pt 7):1425-6.

Identification of a pharmacological target for genioglossus reactivation throughout sleep. Grace KP, Hughes SW, Horner RL. Sleep. 2014 Jan 1;37(1):41-50.

State-dependent and reflex drives to the upper airway: basic physiology with clinical implications. Horner RL, Hughes SW, Malhotra A. J Appl Physiol. 2014 Feb 1;116(3):325-36

K+ channel modulation causes genioglossus inhibition in REM sleep and is a strategy for reactivation. Grace KP, Hughes SW, Shahabi S, Horner RL. Respir Physiol Neurobiol. 2013 Sep 15;188(3):277-88.

State-dependent contribution of the hyperpolarization-activated Na+/K+ and persistent Na+ currents to respiratory rhythmogenesis in vivo. Montandon G, Horner RL. J Neurosci. 2013 May 15;33(20):8716-28.

Identification of the mechanism mediating genioglossus muscle suppression in REM sleep. Grace KP, Hughes SW, Horner RL. Am J Respir Crit Care Med. 2013 Feb 1;187(3):311-9.

5-HT1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity. Grace KP, Liu H, Horner RL. J Neurosci. 2012 Feb 1;32(5):1622-33.

Neural control of the upper airway: integrative physiological mechanisms and relevance for sleep disordered breathing. Horner RL. Compr Physiol. 2012 Jan;2(1):479-535.

PreBotzinger complex neurokinin-1 receptor-expressing neurons mediate opioid-induced respiratory depression. Montandon G, Qin W, Liu H, Ren J, Greer JJ, Horner RL. J Neurosci. 2011 Jan 26;31(4):1292-301.

Textbook Chapters:

Horner RL. Central neural control of respiratory neurons and motoneurons during sleep. In: Principles and Practice of Sleep Medicine (eds. M. H. Kryger, T. Roth, and W. C. Dement), 5th edn, 2011, pp. 237-249. Elsevier.

Horner RL. Autonomic consequences of arousal from sleep and neural mechanisms of arousal. In: Sleep Apnea: Pathogenesis, Diagnosis and Treatment. 2nd edition. Pack AI, ed. Lung Biology in Health and Disease. New York: Informa Healthcare. pp. 128-156. 2011.

Horner RL. Respiratory Physiology. In: Encyclopaedia of Sleep, edited by Kushida C. Waltham, MA: Academic Press, 2013, p. 517-524.

Horner RL, Malhotra A. Control of breathing and upper airways during sleep. In: Murray & Nadel’s Textbook of Respiratory Medicine (eds. V. C. Broaddus, R. J. Mason, J. D. Ernst, T. E.  King, Jr, S. C. Lazarus, J. F. Murray, J. A. Nadel, A. Slutsky, M. Gotway), 6th edn, 2015, pp. 1511-1526. Elsevier.

Horner RL. Central neural control of respiratory neurons and motoneurons during sleep. In: Principles and Practice of Sleep Medicine (eds. M. H. Kryger, T. Roth, and W. C. Dement), 6th edn, in press, 2015. Elsevier.

Horner RL. Central neural control of respiratory neurons and motoneurons during sleep. In: Principles and Practice of Sleep Medicine (eds. M. H. Kryger, T. Roth, and W. C. Dement), 5th edn, 2011, pp. 237-249. Elsevier.

Horner RL. Respiratory Physiology. In: Encyclopaedia of Sleep, edited by Kushida C. Waltham, MA: Academic Press, 2013, p. 517-524.

Horner RL, Malhotra A. Control of breathing and upper airways during sleep. In: Murray & Nadel’s Textbook of Respiratory Medicine Elsevier, in press, (accepted 22/1/14)

Appointments

Director, Sleep and Biological Rhythms Toronto, a CIHR team research and training program
Team Lead, Integrative Program in Sleep, Sedation and Anesthetic Sciences

Courses

Course Number: PSL472H1S
Course Name: