Christophe Proulx, Ph.D.
Deciphering the neural mechanisms of emotions and their contribution to behavior through the brain reward circuits
Professor Christophe Proulx studies the neural mechanisms of emotions underlying normal behavioral responses, but also the defects in these mechanisms that can lead to mood disorders such as depression. Areas of the brain that play an important role in these responses are the reward circuitry of the brain, which includes various limbic system nuclei, the lateral habenula, and the dorsal raphe nucleus.
To understand how emotions are encoded and transmitted in these structures, and how they affect behavior, Proulx's team uses advanced techniques (optical fiber photometry, electrophysiology measurements, optogenetics) that allow them to measure and to manipulate neuronal activity, in real time in free moving animals.
A better understanding of the mechanisms of action of antidepressants
Proulx's research has revealed that the lateral habenula plays a key role in mood regulation and may be involved in depressive behavior. Studies in humans and animals have shown that this structure is activated by unpleasant and stressful situations and affects decision-making and behavior. Overactivity of the habenula may therefore contribute to depression, and a reduction in its activity may relieve depressive symptoms.
Proulx's research also focuses on the effects of antidepressants on the habenula and on the signals transmitted by the brain's reward system in response to treatment.
Our laboratory is interested in molecular mechanisms and neuronal pathways involved in the transmission of affective signals important to orchestrate proper behavioral responses, and identify the cellular and synaptic dysfunctions underlying mood disorders. We are particularly interested by neuronal inputs from the lateral habenula to the serotonergic dorsal raphe nucleus and neuronal serotonergic outputs toward several brain nuclei of the limbic system.
Our main approaches include ex vivo and in vivo optogenetic manipulations, in vivo measurement of neuronal activity using fiber photometry, electrophysiological recordings on brain slices, and several behavioral tests in rodents.
Landgraf, D. et al. Author’s Accepted Manuscript. Biol. Psychiatry 1–30 (2016). doi:10.1016/j.biopsych.2016.03.1050
Shabel, S. J., Proulx, C. D., Piriz, J. & Malinow, R. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment. Science 345, 1494–1498 (2014).
Proulx, C. D., Hikosaka, O. & Malinow, R. Reward processing by the lateral habenula in normal and depressive behaviors. Nat. Neurosci. 17, 1146–1152 (2014).
Nabavi, S. et al. Engineering a memory with LTD and LTP. Nature 511, 348–352 (2014).
Lin, J. Y. et al. Optogenetic Inhibition of Synaptic Release with Chromophore-Assisted Light Inactivation (CALI). Neuron 79, 241–253 (2013).
Shabel, S. J., Proulx, C. D., Trias, A., Murphy, R. T. & Malinow, R. Input to the lateral habenula from the Basal Ganglia is excitatory, aversive, and suppressed by serotonin. Neuron 74, 475–481 (2012).
Li, B. et al. Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature 470, 535–539 (2011).
Proulx, C. D. et al. Mutational analysis of the conserved Asp2.50 and ERY motif reveals signaling bias of the urotensin II receptor. Mol. Pharmacol. 74, 552–561 (2008).
Proulx, C. D. et al. Biological properties and functional determinants of the urotensin II receptor. Peptides 29, 691–699 (2008).
Leclerc, P. C. et al. Ascorbic acid decreases the binding affinity of the AT1 receptor for angiotensin II. Am. J. Hypertens. 21, 67–71 (2008).
Holleran, B. J. et al. Photolabelling the urotensin II receptor reveals distinct agonist- and partial-agonist-binding sites. Biochem. J. 402, 51–61 (2007).
Proulx, C. D. et al. Involvement of a cytoplasmic-tail serine cluster in urotensin II receptor internalization. Biochem. J. 385, 115–123 (2005).
Emotions, serotonin, lateral habenula, optogenetic, fiber photometry, patch clamp, behaviors
2601 Chemin de la Canardière Québec (Québec) G1J 2G3 Canada