Le stress est un moteur essentiel de l’adaptation et la r\u00e9ponse au stress d\u2019un organisme est g\u00e9n\u00e9ralement b\u00e9n\u00e9fique car elle favorise la survie. En cas de danger, le cerveau orchestre la d\u00e9tection et la r\u00e9ponse aux stimuli aversifs environnementaux et guide ainsi la s\u00e9lection de la strat\u00e9gie d’adaptation la plus appropri\u00e9e parmi un r\u00e9pertoire diversifi\u00e9 de comportements d\u00e9fensifs. Ces comportements inn\u00e9s et acquis ont \u00e9t\u00e9 fa\u00e7onn\u00e9s par la s\u00e9lection naturelle et conserv\u00e9s \u00e0 la fois chez les invert\u00e9br\u00e9s et les vert\u00e9br\u00e9s. Ils comprennent des strat\u00e9gies passives telles que le \u00ab\u00a0freezing\u00a0\u00bb (ou immobilit\u00e9) et des r\u00e9ponses actives \u00ab\u00a0fight or flight\u00a0\u00bb (combat ou fuite), et le passage entre ces modes passifs\/actifs est essentiel pour la flexibilit\u00e9 comportementale. Le freezing est une r\u00e9ponse universelle \u00e0 la peur caract\u00e9ris\u00e9e par une absence totale de mouvement, \u00e0 part la respiration, due \u00e0 une posture corporelle tendue lorsqu’une menace est rencontr\u00e9e. Le freezing est essentiel dans les processus de gestion du stress, car il correspond \u00e0 un \u00e9tat d’hypervigilance qui permet de prendre des d\u00e9cisions et, par cons\u00e9quent, d’\u00e9laborer la strat\u00e9gie comportementale la plus pertinente. Bien que le freezing soit pertinent pour l’\u00e9tiologie des troubles li\u00e9s \u00e0 la peur tels que les troubles de stress post-traumatique, les attaques de panique et les phobies sociales, les circuits neuronaux et les substrats cellulaires sous-jacents sont loin d’\u00eatre bien compris.<\/p>\n
Pour aborder cette question, nous avons combin\u00e9 des approches par \u00e9lectrophysiologie ex vivo et in vivo coupl\u00e9es \u00e0 des outils de pharmaco- et optog\u00e9n\u00e9tiques compl\u00e9t\u00e9es par des analyses par microscopie. Nous avons utilis\u00e9 un mod\u00e8le pr\u00e9clinique d\u2019exposition \u00e0 un stimulus aversif et mesurer les r\u00e9ponses imm\u00e9diates de freezing. Nous avons mis en \u00e9vidence de nouvelles structures clefs modulant ce comportement de d\u00e9fense. Ces structures c\u00e9r\u00e9brales relient les neurones GABAergiques du tegmentum lat\u00e9ro-dorsal (LDTg) qui projettent vers l\u2019aire tegmentale ventrale (ATV), une structure bien connue pour son r\u00f4le dans les r\u00e9ponses li\u00e9es \u00e0 la r\u00e9compense. Au sein de l\u2019ATV, ce sont \u00e9galement les neurones GABAergiques de projection qui transmettent ensuite cette information \u00e0 l’amygdale c\u00e9r\u00e9brale. L’activation du triumvirat LDTg-ATV-Amygdale par des \u00e9v\u00e9nements aversifs permet de mieux comprendre les processus c\u00e9r\u00e9braux d’adaptation au stress. Ces r\u00e9sultats remettent notamment en question la vision accept\u00e9e de l’axe LDTg-ATV qui a \u00e9t\u00e9 historiquement li\u00e9 \u00e0 la r\u00e9compense et aux processus de renforcement.<\/p>\n
<\/p>\n
R\u00e9f\u00e9rence\u00a0:<\/p>\n
A non-canonical GABAergic pathway to the VTA promotes unconditioned freezing<\/p>\n
Lo\u00efc Broussot 1, 2*, Thomas Contesse 1, 2*, Renan Costa-Campos1, 2, Christelle Glangetas3, L\u00e9a Royon 1, 2, Hugo Fofo 1, 2, Thomas Lorivel 2, Fran\u00e7ois Georges 3, Sebastian P. Fernandez 1, 2, 4 and Jacques Barik 1, 2, 4.<\/p>\n
1 Universit\u00e9 C\u00f4te d\u2019Azur, Nice, France.<\/p>\n
2 Institut de Pharmacologie Mol\u00e9culaire & Cellulaire, CNRS UMR7275, Valbonne, France.<\/p>\n
3 Universit\u00e9 de Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.<\/p>\n
4 Co-last and co-corresponding authors.<\/p>\n
<\/p>\n
L\u00e9gende de la figure :<\/p>\n
Gauche\u00a0: coupe coronale de cerveau contenant la r\u00e9gion du noyau lat\u00e9rodorsal du tegmentum (LDTg)\u00a0; les neurones GABAergiques de cette structure sont identifiables gr\u00e2ce \u00e0 l\u2019expression restreinte de la prot\u00e9ine fluorescente mCherry. Centre\u00a0: sch\u00e9ma d\u2019un cerveau en 3D de souris permettant de visualiser le circuit neuronal (LDTg->VTA->Amygdale) identifi\u00e9 dans l\u2019\u00e9tude Broussot et al., mettant en \u00e9vidence son r\u00f4le dans la modulation du comportement de freezing chez l\u2019animal vigile (droite).<\/p>\n
<\/p>\n
Contact\u00a0:<\/p>\n
Jacques Barik<\/p>\n
Maitre de Conf\u00e9rences, Universit\u00e9 C\u00f4te d\u2019Azur<\/p>\n
barik@ipmc.cnrs.fr<\/p>\n
04 93 95 34 43<\/p>\n
Institut de Pharmacologie Mol\u00e9culaire et Cellulaire<\/p>\n
CNRS \u2013 Univesit\u00e9 C\u00f4te d\u2019Azur.<\/p>\n
660 route des Lucioles<\/p>\n
06560 Sophia Antipolis, Valbonne<\/p>\n
<\/p>\n
English Summary<\/em><\/strong><\/p>\n Stress is a key motor of adaptation The stress response is mostly beneficial as it promotes survival. In the event of danger, the brain orchestrates the detection of and response to aversive environmental stimuli and thus guides the selection of the most appropriate coping strategy from a diverse repertoire of defensive behaviours. These innate and acquired behaviours have been shaped by natural selection and conserved in both invertebrates and vertebrates. They include passive strategies such as freezing and active ‘fight or flight’ responses, and switching between these passive\/active modes is essential for behavioural flexibility. Freezing is a universal fear response characterised by a complete absence of movement, apart from breathing, due to tense body posture when a threat is encountered. Freezing is essential in stress management processes, as it corresponds to a state of hypervigilance that allows for decision making and, consequently, the development of the most appropriate behavioural strategy. Although freezing is relevant to the etiology of fear-related disorders such as post-traumatic stress disorder, panic attacks and social phobias, the underlying neural circuitry and cellular substrates are far from being well understood.<\/em><\/p>\n To address this issue, we combined ex vivo and in vivo electrophysiology approaches coupled with pharmaco- and optogenetic tools complemented by microscopy analyses. We used a preclinical model of exposure to an aversive stimulus and measured the immediate freezing responses. We identified new key structures modulating this defensive behaviour. These brain structures connect GABAergic neurons in the lateral-dorsal tegmentum (LDTg) that project to the ventral tegmental area (VTA), a structure well known for its role in reward-related responses. Within the VTA, it is also the GABAergic projection neurons that then transmit this information to the amygdala. The activation of the LDTg-ATV-Amygdala triumvirate by aversive events provides a better understanding of the brain’s processes of adaptation to stress. In particular, these results challenge the accepted view of the LDTg-ATV axis, which has historically been linked to reward and reinforcement processes.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Le stress est un moteur essentiel de l’adaptation et la r\u00e9ponse au stress d\u2019un organisme est g\u00e9n\u00e9ralement b\u00e9n\u00e9fique car elle favorise la survie. En cas de danger, le cerveau orchestre la d\u00e9tection et la r\u00e9ponse aux stimuli aversifs environnementaux et guide ainsi la s\u00e9lection de la strat\u00e9gie d’adaptation la plus appropri\u00e9e parmi un r\u00e9pertoire diversifi\u00e9 […]<\/p>\n","protected":false},"author":4,"featured_media":17637,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[31],"class_list":["post-17647","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-actualite-en"],"publishpress_future_action":{"enabled":false,"date":"2026-04-22 09:00:20","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\/17647","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=17647"}],"version-history":[{"count":0,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/17647\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media\/17637"}],"wp:attachment":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media?parent=17647"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/categories?post=17647"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/tags?post=17647"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}