Selon l\u2019Organisation Mondiale de la Sant\u00e9, la d\u00e9pression est un trouble mental courant affectant plus de 300 millions de personne dans le monde. L\u2019apparition de troubles d\u00e9pressifs est la cons\u00e9quence d\u2019une interaction complexe entre pr\u00e9dispositions g\u00e9n\u00e9tiques et facteurs psychosociaux. Elle se caract\u00e9rise notamment par une perte de plaisir (anh\u00e9donie) et l\u2019\u00e9vitement des autres (aversion sociale). Ces alt\u00e9rations comportementales peuvent \u00eatre observ\u00e9es chez des souris soumises \u00e0 des exp\u00e9riences traumatoge\u0300nes comme un stress social. En effet, l\u2019exposition r\u00e9p\u00e9t\u00e9e de souris \u00e0 des cong\u00e9n\u00e8res m\u00e2les dominants entraine l\u2019apparition de troubles comportementaux caract\u00e9ristiques de la d\u00e9pression associ\u00e9s \u00e0 la d\u00e9r\u00e9gulation d\u2019un messager chimique du cerveau, la dopamine.\u00a0 Comprendre les m\u00e9canismes impliqu\u00e9s dans ces adaptations est un enjeu important pour le traitement des troubles psychiatriques li\u00e9s au stress.<\/p>\n
Les r\u00e9cents travaux de notre \u00e9quipe au sein de l\u2019Institut de Pharmacologie Mol\u00e9culaire et Cellulaire, publi\u00e9s dans la revue Nature Communications, ont d\u00e9voil\u00e9 en partie les m\u00e9canismes neurobiologiques impliqu\u00e9s dans les troubles d\u00e9pressifs. Nous avons identifi\u00e9 un circuit neuronal qui sous-tend la d\u00e9r\u00e9gulation des signaux dopaminergiques et l\u2019apparition des comportements anh\u00e9doniques et d\u2019aversion sociale. En effet, nous avons montr\u00e9 que l\u2019exposition \u00e0 un stress social chronique entraine une profonde d\u00e9r\u00e9gulation des neurones du noyau lat\u00e9rodorsal du tegmentum (LDTg), notamment ceux produisant l\u2019ac\u00e9tylcholine, un messager chimique jouant un r\u00f4le important dans la modulation de l\u2019activit\u00e9 des neurones dopaminergiques. Le blocage s\u00e9lectif de l\u2019activit\u00e9 de ces neurones par l\u2019utilisation d\u2019approches chimiog\u00e9n\u00e9tiques lors des phases d\u2019exposition au stress est suffisante pour emp\u00eacher la cascade de r\u00e9actions aboutissant \u00e0 l\u2019apparition des troubles comportementaux. La d\u00e9r\u00e9gulation des neurones \u00e0 ac\u00e9tylcholine est caus\u00e9e par le relargage de corticolib\u00e9rine et sa fixation sur le r\u00e9cepteur CRF de type 1 modulant directement l\u2019activit\u00e9 des neurones cholinergiques.<\/p>\n
Ces r\u00e9sultats pourraient mener \u00e0 de nouvelles pistes th\u00e9rapeutiques pour combattre la d\u00e9pression, soit par des approches pharmacologiques contre les cibles mol\u00e9culaires identifi\u00e9es, soit par des approches permettant de moduler l\u2019activit\u00e9 des macrocircuits mis en \u00e9vidence.<\/p>\n
<\/p>\n
Reference<\/p>\n
<\/p>\n
Fernandez SP, Broussot L, Marti F, Contesse T, Mouska X, Soiza-Reilly M, Marie H, Faure P, Barik J.<\/p>\n
Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors.<\/p>\n
Nat Commun. 2018 Oct 25;9(1):4449. doi: 10.1038\/s41467-018-06809-7.<\/p>\n
<\/p>\n
Contact chercheur<\/p>\n
<\/p>\n
Jacques Barik<\/p>\n
Universit\u00e9 C\u00f4te d\u2019Azur, Nice, 06560, France<\/p>\n
Institut de Pharmacologie Mol\u00e9culaire & Cellulaire, CNRS, UMR7275, Valbonne, France<\/p>\n
barik@ipmc.cnrs.fr<\/p>\n
<\/p>\n
Estimates from the WHO show that depression is one of the most common psychiatric disorders, affecting 300 million people worldwide. Depression appears to be the result of a complex interaction between genetic predisposition and psychosocial factors. Most common symptoms include decrease ability to experience pleasure (anhedonia) and strong withdrawal from social interaction. These behavioral traits can be modeled and studied in mice subjected to stressful events such as social defeat. Indeed, in mice repeated exposure to a dominant conspecific produces depressive-like behavioral alterations that have been associated with an imbalance in the brain neurotransmitter dopamine. Understanding the process underlying these mal-adaptations warrants better treatments for psychiatric disorders associated with stress.<\/p>\n
In a recent work published by our team (Institute of Molecular and Cellular Pharmacology) in the journal Nature Communications, we unraveled a novel mechanism implicated in the neurobiology of depression. We identified a neuronal circuit that promotes a dysregulation in dopaminergic signaling and the appearance of social aversion and anhedonia, two hallmarks of depressive states. We showed that exposure to chronic social stress induces strong activation of cholinergic neurons in the laterodorsal tegmental (LDTg) nucleus, which are important regulators of dopamine neurons activity. Selective chemogenetic silencing of these cholinergic neurons during social stress exposure was sufficient to prevent the chain of events linked with maldaptive behavioral responses. The dysregulation of LDTg cholinergic neurons by stress involves the release of corticotrophin-releasing factor (CRF) and selective activation of CRF-1 receptors in these neurons.<\/p>\n
These results will open up new avenues in the fight against depression, by pinpointing a molecular target for drug discovery, or alternatively by brain neuromodulation approaches on these newly described circuit mechanisms.<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n","protected":false},"excerpt":{"rendered":"
Selon l\u2019Organisation Mondiale de la Sant\u00e9, la d\u00e9pression est un trouble mental courant affectant plus de 300 millions de personne dans le monde. L\u2019apparition de troubles d\u00e9pressifs est la cons\u00e9quence d\u2019une interaction complexe entre pr\u00e9dispositions g\u00e9n\u00e9tiques et facteurs psychosociaux. Elle se caract\u00e9rise notamment par une perte de plaisir (anh\u00e9donie) et l\u2019\u00e9vitement des autres (aversion sociale). […]<\/p>\n","protected":false},"author":4,"featured_media":10152,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[31],"class_list":["post-10155","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-actualite-en"],"publishpress_future_action":{"enabled":false,"date":"2026-04-24 12:16:38","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/10155","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/comments?post=10155"}],"version-history":[{"count":1,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/10155\/revisions"}],"predecessor-version":[{"id":10157,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/10155\/revisions\/10157"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media\/10152"}],"wp:attachment":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media?parent=10155"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/categories?post=10155"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/tags?post=10155"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}