M.Sc. and Ph.D. programs were completed at Universite Laval (Quebec City, 1997) and Universite de Montreal (Montreal, 2003) under the supervision of Drs. Helene Bachelard and Rejean Couture, respectively. Both projects were investigating the potential role of central neuropeptides (opioids and tachykinins) and their G protein-coupled receptors on cardiovascular function in normotensive and hypertensive rats. The projects involved stereotaxic surgery and drug microinjection into discrete brain regions. After my Ph.D. training, I moved to the Weill Cornell Medical College in New York City to learn neuroanatomy at Dr. Virginia Pickel's laboratory, in the Division of Neurobiology. More precisely, I learned immunocytochemistry, electron microscopy and confocal microscopy. My postdoctoral project combined neurophysiology and neuroanatomy to investigate G protein-coupled receptor's plasticity following dopamine activation. I got promoted Instructor in 2006, and stayed in the same laboratory until 2008. In 2009, I joined the Maryland Psychiatric Research Center as the head of the electron microscopy facility, as well as the Director of the Maryland Brain Collection.
Multiple circuits in the central nervous system relay information on complex behaviors such as stress and motivation/reward. These projection neurons are connecting several nucleus and areas of the basal ganglia and the limbic system. Regions of the ventral tegmental area, striatum, prefrontal cortex and amygdala represent target areas that are highly involved in behavioral function. Chemical imbalances of these pathways have been associated with psychiatric disorders, namely schizophrenia and stress-related disorders as anxiety.
The tachykinin family of neuropeptides and their G protein-coupled receptors are modulators of these brain projections. Their subcellular distributions and plasticity in phenotypically characterized neurons, however, remain poorly understood. The main goals of my studies are to determine 1) the ultrastructural locations of tachykinin receptors NK-1 and NK-3 in regions of the mesocorticolimbic circuitry and, 2) their trafficking following stress or dopamine activation. The neuroanatomy of tachykinin receptors is investigated using immunocytochemistry and tract-tracers microinjected into several brain areas. These methods enable dual immunolabeling that identify the receptors on selected projection neurons (dopaminergic, glutamatergic) or local neurons (GABAergic interneurons). In addition, high resolution electron microscopy provides critical answers related to the receptor function by giving evidences of the receptor's location in pre- or post-synaptic profiles, in the cytoplasm or on the plasma membrane in neurotransmitter-characterized neurons. Pharmacological (drug administration), and behavioral tools (plus-maze, prepulse inhibition to acoustic startle) also are assessed to validate schizophrenia- or stress-like paradigms.
Lab Techniques and Equipment:
- Electron microscopy
Hether, S., Misono, K. and Lessard, A.: The neurokinin-3 receptor (NK3R) antagonist SB222200 prevents the apomorphine-evoked surface but not nuclear NK3R redistribution in dopaminergic neurons of the rat ventral tegmental area (VTA). Neuroscience, 247: 12-24, 2013.
Misono, K and Lessard, A.: Apomorphine-evoked redistribution of neurokinin-3 (NK3) receptors in dopaminergic dendrites and neuronal nuclei of the rat ventral tegmental area. Neuroscience, 203: 27-38 2012.
Lessard, A., Coleman, C.G. & Pickel, V.M.: Chronic intermittent hypoxia reduces neurokinin-1 (NK1) receptor density in small dendrites of non-catecholaminergic neurons in mouse nucleus tractus solitarius. Exp. Neurol, 223(2): 634-44 2010.
Lessard, A., Savard, M., Gobeil, F. Jr., Pierce, J.P. & Pickel, V.M. : The neurokinin-3 (NK3) and the neurokinin-1 (NK1) receptors are differentially targeted to mesocortical and mesolimbic projection neurons, and to neuronal nuclei in the rat ventral tegmental area. Synapse, 63(6): 484-501 2009.
Lane, D.A., Lessard, A., Chan, J., Colago, E.E., Zhou, Y., Schlussman, S., Kreek, M.J. and Pickel, V.M.: Region-Specific Changes in the Distribution of AMPA Receptor GluR1 Subunits in the Rat Ventral Tegmental Area Following Acute or Chronic Morphine Administration. J.Neurosci., 28 (39): 9670-81 2008.
Lessard, A., Grady E.F., Bunnett, N.W. & Pickel, V.M. Predominant surface distribution of neurokinin-3 (NK3) receptors in non-dopaminergic dendrites in the rat substantia nigra and ventral tegmental area. Neuroscience, 144 (4): 1393-1408 2007.
Lessard, A. & Pickel, M. : Subcellular distribution and plasticity of neurokinin-1 (NK1) receptor in the rat substantia nigra and ventral tegmental area. Neuroscience, 135:1309-1323 2005.
Lessard, A., Laurin, M., Yamaguchi, N. & Couture, R. : Central anti-hypertensive effect of tachykinin NK-3 receptor antagonists in spontaneously hypertensive rat. Eur. J. Pharmacol., 486:75-83 2004.
Lessard, A., Campos, M.M., Neugebauer, W. & Couture, R. : Implication of nigral tachykinin NK3 receptors in the maintenance of hypertension in spontaneously hypertensive rats : a pharmacologic and autoradiographic study. Br. J. Pharmacol., 138 (4): 554-563 2003.
Lessard, A. & Bachelard, H.: Tonic inhibitory control exerted by opioid peptides in the hypothalamic paraventricular nucleus on systemic and regional haemodynamics in awake rats. Br. J. Pharmacol, 136 (5): 753-763 2002.
Lessard, A. & Couture, R. : Modulation of cardiac activity by tachykinins in the rat substantia nigra. Br. J. Pharmacol, 134 (8): 1749-1759 2001.
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