Senior Scientist, Neuroscience, Ottawa Hospital Research Institute

Associate Director, Ottawa Hospital Research Institute

Professor, Department of Medicine, Division of Neurology, Department of Molecular and Cellular Medicine, University of Ottawa

Synaptic transmission, neurotransmitters, neuropeptides

Neural control of neuroendocrine and autonomic function

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, brainstem 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, immunocytochemistry, early gene (c-Fos) expression, in-situ hybridization, electron microscopy and radioimmunoassay.

Earlier electrophysiological studies revealed that the excitability of magnocellular neurosecretory neurons in the hypothalamic supraoptic and paraventricular nuclei governs hormone (vasopressin and oxytocin) release from their posterior pituitary axon terminals. CNS control of posterior pituitary hormone secretion requires characterization of the factors that control the excitability of magnocellular neurosecretory neurons. In-vivo this research is focused on defining CNS circuitry that conveys information to these cells from osmoreceptors, baroreceptors, volume receptors, and circumventricular organs. In-vitro slice, explant, and dissociated cell preparations together with intracellular and patch clamp techniques are used to define intrinsic membrane properties and ligand-gated conductances that are unique to the magnocellular neurons, and to cells located along the lamina terminalis whose axons synapse directly with magnocellular neurons. This knowledge will contribute to understanding how the brain senses and adjusts for moment to moment alterations in hydromineral balance and cardiovascular functions. (Funded by The Canadian Institutes of Health Research (CIHR)).

The hypothalamus is a major contributor to central regulation of autonomic functions, and specific populations of medial hypothalamic neurons project their axons directly to brainstem and spinal autonomic centres. Participating in these descending pathways are vasopressin and oxytocin-immunoreactive parvocellular neurons in the paraventricular nucleus, whose axons target spinal preganglionic neurons located in the intermediolateral cell column. Using patch clamp and double-label techniques, Dr Renaud's lab is investigating signalling mechanisms in spinal preganglionic neurons from descending and local pathways, their neuropharmacology and signalling at G-protein-coupled vasopressin and oxytocin receptors. (Funded by The Canadian Institutes of Health Research (CIHR)).

Mammals are known to demonstrate diurnal rhythms in various neuroendocrine and cardiovascular functions, rhythms that may contribute to the time of occurrence of cerebral and/or myocardial ischemic events. Central control of neuroendocrine and autonomic functions reside with at least three different populations of "output" neurons located in the hypothalamic paraventricular nucleus, whereas the central source of the diurnal rhythmicity is believed to reside within neurons in the adjacent suprachiasmatic nucleus, a circadian pacemaker in mammalian brain. On the hypothesis that suprachiasmatic nucleus neurons transfer their rhythmicity synaptically to different populations of paraventricular nucleus output cells, Dr Renaud has initiated another series of collaborative investigations intended to characterize the synaptic connectivity and neurotransmitters involved in suprachiasmatic nucleus inputs to paraventricular nucleus neurons. A variety of techniques serve to differentiate paraventricular nucleus neurons according to their axon targets: to the median eminence, to regulate anterior pituitary function; the posterior pituitary, to regulate plasma vasopressin and oxytocin levels; to brainstem and spinal cord autonomic centres, to control cardiovascular and adrenomedullary function. (Funded by the Heart and Stroke Foundation).

Major Awards/Affiliations

Affiliations

1999-present University of Ottawa, Director, Research, Department of Medicine

2001 - present Associate Director, Ottawa Hospital Research Institute