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Senior Scientist, Neuroscience, Ottawa Hospital Research Institute
Associate Director, Ottawa Hospital Research Institute
Professor Emeritus, Department of Medicine, Division of Neurology, Department of Cellular and Molecular Medicine, University of Ottawa
- 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.
midline thalamus, spinal preganglionic neurons, gastrin releasing polypeptide, TRH, Nitric Oxide, Connexin36