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.