Leo Renaud, MD, PhD, FRCPC, FRSC
lprenaud@ohri.ca
Senior Scientist, Neuroscience, Ottawa Hospital Research Institute
Associate Director, Ottawa Hospital Research InstituteProfessor Emeritus, Department of Medicine, Division of Neurology, Department of Cellular and Molecular Medicine, University of Ottawa
Research Interests
Synaptic transmission, neurotransmitters, neuropeptides
Neural control of neuroendocrine and autonomic function
Major research activities
Dr. Renaud is interested in the neurophysiology and pharmacology of synaptic transmission in the mammalian central nervous system with a particular interest in defining the cellular and molecular neuronal mechanisms operative in hypothalamic, thalamic and spinal cord circuits that subserve neuroendocrine and autonomic functions. The approach is multidisciplinary, applied to both in vivo and in vitro preparations, and uses extra- and intracellular electrophysiology, patch clamp techniques, chemospecific lesions, anterograde and retrograde tracers, and immunocytochemistry.
An appreciation of the cellular and molecular neurobiology of select neuronal systems in the spinal cord and thalamus in rodent models has relevance to addressing dysfunctional mechanisms that may contribute to the pathophysiology of diseases of aging (e.g. hypertension, obesity) and mental disorders (e.g. anxiety, depression, addicition). Two themes relate to ongoing research:
A: Factors regulating excitability in spinal sympathetic preganglionic neurons (SPNs). Mammals rely critically on the sympathetic nervous system to orchestrate a range of physiological and behavioral responses that permit adaptation to, and survival from major stressors. SPNs located in the lateral spinal column are the critical source of neural commands designed to regulate the activity of target organs and systems. However, little is known about their cellular neurobiology, information that may help identify potential therapeutic targets disorders attributed to excessive sympathetic activity. Using patch clamp techniques in in-vitro spinal cord slice preparations, immunocytochemistry and behavior studies, our objectives include characterizing the properties (and functions) of gap junctional electrical coupling in rodent SPNs, identifying deficits (electrical, metabolic) in a connexin Cx36-/- model, and characterizing postsynaptic and possible presynaptic actions of nitric oxice in regulating SPN excitability and modulating electrical coupling.
B: Converging circadian, arousal and stress signaling pathways in the midline and intralaminar thalamus. Coordinated activity among specific hypothalamic and thalamic neurons is essential to homeostasis in sleep-wake cycles and circadian rhythms in various physiological functions. Interruption in these rhythms is detrimental to mental and physical health. Our interest is the midline thalamic paraventricular nucleus (PVT). PVT receives inputs from the suprachiasmatic nuclei (SCN), site of the brain's master biological clock, from several wakefulness- and feeding-promoting centers, and sites associated with reward and addiction. PVT neurons innervate the prefrontal cortex, amygdala and accumbens, forebrain structures known to have key roles in motivational and addictive behaviors. PVT is a midline thalamic component of a central reward/addiction-prone circuitry, and may contribute to limbic and intractable epilepsy, and schizophrenia. The neurobiology of PVT and neighboring midline thalamic neurons is scant. Our objective is to characterize in the rodent model the intrinsic properties and neuropharmacology of PVT (and other dorsal midline thalamus) neurons, information that may lead us to identify novel approaches to treatment of anxiety, depressive and addictive clinical disorders. Using patch clamp and calcium imaging techniques, the initial focus will seek to define the intracellular signaling involved in conductances that are unique to midline thalamic neurons and govern their bursting and oscillatory behavior over the day-night continuum. PVT receives a convergence of catecholaminergic and neuropeptidergic fibers, and expresses a complexity of specific receptors. We seek to define roles for metabotropic receptors for glutamate and GABA, and receptors for a variety of endogenous neuropeptides.
Major Awards/Affiliations
Affiliations
2001 - present Associate Director, Ottawa Hospital Research Institute
Awards & Honours
2005 Distinguished Scientist Award, Canadian Society of Clinical Investigation
2005 Biomedical Science Ambassador Award, FCIHR; Partners in Research
2005 University of Ottawa Alumni, Faculty of Medicine, University of Ottawa
2003 Award of Excellence, University of Ottawa, Faculty of Medicine
2002 Career Achievement Award, Ottawa Life Sciences Council
2001 David Grimes Career Achievement Award, Ottawa Hospital Foundation
2000 Fellow, Royal Society of Canada
1998 Sarrazin Lecturer, Canadian Physiological Society
Most Recent Publications (provided by The Ottawa Hospital Library Database)
Hermes ML;Kolaj M;Doroshenko P;Coderre E;Renaud LP;, (2009 Sep), Effects of VPAC2 receptor activation on membrane excitability and GABAergic transmission in subparaventricular zone neurons targeted by suprachiasmatic nucleus, Journal of Neurophysiology, Vol.102, Issue 3, 1834-1842 -> view abstract
Zhang L;Renaud LP;Kolaj M;, (2009 Jun), Properties of a T-type Ca2+channel-activated slow afterhyperpolarization in thalamic paraventricular nucleus and other thalamic midline neurons, Journal of Neurophysiology, Vol.101, Issue 6, 2741-2750 -> view abstract
Doroshenko P;Renaud LP;, (2009 Feb 18), Acid-sensitive TASK-like K(+) conductances contribute to resting membrane potential and to orexin-induced membrane depolarization in rat thalamic paraventricular nucleus neurons, Neuroscience, Vol.158, Issue 4, 1560-1570 -> view abstract
Kolaj M;Coderre E;Renaud LP;, (2008 Sep 9), Orexin peptides enhance median preoptic nucleus neuronal excitability via postsynaptic membrane depolarization and enhancement of glutamatergic afferents, Neuroscience, Vol.155, Issue 4, 1212-1220 -> view abstract
Oz M;Yang KH;Shippenberg TS;Renaud LP;O'Donovan MJ;, (2007 Sep), Cholecystokinin B-type receptors mediate a G-protein-dependent depolarizing action of sulphated cholecystokinin ocatapeptide (CCK-8s) on rodent neonatal spinal ventral horn neurons, Journal of Neurophysiology, Vol.98, Issue 3, 1108-1114 -> view abstract
Kolaj M;Renaud LP;, (2007 May), Presynaptic alpha-adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum lamina terminalis2, American Journal of Physiology - Regulatory Integrative & Comparative Physiology, Vol.292, Issue 5, R1907-R1915
Kolaj M;Doroshenko P;Yan C;Coderre E;Renaud LP;, (2007 Jul 29), Orexin-induced modulation of state-dependent intrinsic properties in thalamic paraventricular nucleus neurons attenuates action potential patterning and frequency1, Neuroscience, Vol.147, Issue 4, 1066-1075
van den Top M;Lyons DJ;Lee K;Coderre E;Renaud LP;Spanswick D;, (2007 Feb 9), Pharmacological and molecular characterization of ATP-sensitive K(+) conductances in CART and NPY/AgRP expressing neurons of the hypothalamic arcuate nucleus, Neuroscience, Vol.144, Issue 3, 815-824 -> view abstract
Zhang L;Kolaj M;Renaud LP;, (2006 Sep 15), Suprachiasmatic nucleus communicates with anterior thalamic paraventricular nucleus neurons via rapid glutamatergic and gabaergic neurotransmission: state-dependent response patterns observed in vitro4, Neuroscience, Vol.141, Issue 4, 2059-2066
Richter TA;Kolaj M;Renaud LP;, (2006 Sep), Heterogeneity in low voltage-activated Ca2+ channel-evoked Ca2+ responses within neurons of the thalamic paraventricular nucleus3, European Journal of Neuroscience, Vol.24, Issue 5, 1316-1324
