Venue: Centre Broca
Benoit Labonté
Associate Professor
Université Laval – Canada
Invited by Anna Beyeler (Magendie)
Title
Dissecting the functional and molecular deficits at the cortico tegmental pathway in stressed males and females.
Abstract
The medial prefrontal cortex (mPFC) is a central hub region for the processing of emotional and stressful environmental information. Recent studies by us and others suggest that cortically driven dysregulation of subcortical circuits underlies the expression of depressive-like behaviors in humans and chronically stressed animals. More precisely, our group showed that stress changes the excitatory/inhibitory balance at cortical neurons projecting to the nucleus accumbens ( and the ventral tegmental area (VTA) differently in males and females. Importantly, these alterations are accompanied by an important reorganization of pathway specific gene programs in a sex dependent fashion. How do these stress driven changes occurring in the mPFC affect synaptic transmission in downstream output brain structures in males and females, and which transcriptional changes underlie these effects?
In this talk, I will introduce novel and previously unpublished data characterizing the role of the cortico tegmental mPFC VTA pathway in the expression of stress responses I will present results obtained by combining optogenetics with patch electrophysiology and pharmacological approaches to reveal the cellular mechanisms underlying the activity of this pathway at baseline and under stress conditions. These results come with a variety of assays combined with pharmacogenetic and optogenetic manipulations to define the behavioral contribution of this
pathway at baseline and in the context of stress. Finally, I will show results from our transcriptional analyses highlighting targets that may be responsible for the functional and behavioral impact of stress in a sex specific fashion. Globally I will provide a multidisciplinary perspective on the molecular mechanisms underlying the functional impact of chronic stress on the activity of the cortico teg mental pathway in males and females.
Selected publications
Mansouri S, Pessoni AM, Rivera AM, Tamminga CA, Parise E, Turecki G, Nestler EJ, Chen TH, Labonté B. Transcriptional dissection of symptomatic profiles across the brain of men and women with depression. Nat Commun. 2023 Oct 26;14(1):6835. doi: 10.1038/s41467-023-42686-5.
Bittar TP, Labonté B. Functional Contribution of the Medial Prefrontal Circuitry in Major Depressive Disorder and Stress-Induced Depressive-Like Behaviors. Front Behav Neurosci. 2021 Jun 21;15:699592. doi: 10.3389/fnbeh.2021.699592.
Bittar TP, Pelaez MC, Hernandez Silva JC, Quessy F, Lavigne AA, Morency D, Blanchette LJ, Arsenault E, Cherasse Y, Seigneur J, Timofeev I, Sephton CF, Proulx CD, Labonté B. Chronic Stress Induces Sex-Specific Functional and Morphological Alterations in Corticoaccumbal and Corticotegmental Pathways. Biol Psychiatry. 2021 Aug 1;90(3):194-205. doi: 10.1016/j.biopsych.2021.02.014.
Quessy F, Bittar T, Blanchette LJ, Lévesque M, Labonté B. Stress-induced alterations of mesocortical and mesolimbic dopaminergic pathways. Sci Rep. 2021 May 26;11(1):11000. doi: 10.1038/s41598-021-90521.
Scarpa JR*, Fatma M*, Loh YHE*, Traore R, Stefan T, Chen TH, Nestler EJ, Labonté B. Shared Transcriptional Signatures in Major Depressive Disorder and Mouse Chronic Stress Models, Biol Psychiatry, 2020. Jan 22: S0006-3223(20)30011-1. doi: 10.1016/j.biopsych.2019.12.029.
Labonté B*, Abdallah K, Maussion G, Yerko V, Yang J, Bittar T, Quessy F, Golden SA, Navarro L, Checknita D, Gigek C, Lopez JP, Neve RL, Russo SJ, Tremblay RE, Côté G, Meaney MJ, Mechawar N, Nestler EJ, Turecki G* Regulation of impulsive-aggressive behaviors by a novel lincRNA. Mol Psychiatry. 2020 Jan 6. doi: 10.1038/s41380-019-0637-4. * co-corresponding authors.
Labonte B, Engmann O, Purushothaman I, Ménard C, Wang J, Tan C, Scarpa JR, Moy G, Loh YHE, Cahill M, Lorsh Z, Hamilton PJ, Calipari ES, Hodes GE, Issler O, Kronman H, Pfau M, Obradovic A, Dong Y, Neve R, Russo S, Kazarskis A, Tamminga C, Mechawar N, Turecki G, Zhang B, Shen L, and Nestler E. Sex-specific transcriptional signatures in the brain of males and females with major depressive disorders. Nature Medicine. 2017 Sep;23(9):1102-1111. doi: 10.1038/nm.4386.