HEИндивидуална стипендия2024–2026

DefenCB1 · Deciphering the role of striatal CB1 receptors in defensive behaviours

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2024-05-01 → 2026-04-30
Финансиране от ЕС: 210 743 €
Участници: 3
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Рецепторите CB1 в стриатума на мозъка регулират избора между пасивна защита, като замръзване, и активен опит за бягство при заплаха. Разбирането на тези механизми помага да се разберат биологичните причини за тревожните и настроениевите разстройства.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Deciphering the role of striatal CB1 receptors in defensive behaviours

Adaptive responses to danger are essential for survival and involve a balance between passive defensive behaviors, such as freezing, and active responses, such as escape. This balance, known as the active-passive trade-off, allows individuals to cope effectively with threats. Disruptions in the active-passive trade-off can lead to maladaptive coping strategies that are characteristic of anxiety and mood disorders, among the most burdensome psychiatric conditions worldwide. Despite their importance, the neural mechanisms regulating this active-passive trade-off remain poorly understood. This project addressed this gap by investigating how the endocannabinoid system, and specifically cannabinoid type-1 (CB1) receptors in the striatum, regulate defensive behavioral choices under innate and learned threat conditions. The striatum is known to play a central role in action selection and behavioral flexibility, with striatal CB1 receptors acting as key modulators of these processes. However, their contribution to adaptive coping strategies had not been systematically explored. The project aimed to: (1) establish robust behavioral paradigms to study active-passive trade-off in innate and learned configurations; (2) determine how distinct striatal CB1 receptor populations regulate active and passive defensive responses; and (3) identify the underlying synaptic and molecular mechanisms. To achieve these goals, the project combined advanced behavioral analysis with genetic, optogenetic, telemetry, and molecular approaches. By uncovering the mechanisms through which endocannabinoid signaling shaped responses to threat, the project advanced understanding of the biological basis of adaptive and maladaptive coping. In the longer term, the knowledge generated was expected to support the identification of new therapeutic targets for anxiety and mood disorders. The project also generated novel experimental tools and paradigms that could facilitate future research in the stress and mental health fields.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Defensive behaviours are fundamental for survival. Due to threat diversity, organisms adopt active (e.g. escape) or passive (e.g. freeze) defensive strategies to respond accordingly. The balance between active and passive responses can be defined as ""Active-Passive Trade-off"" (APT) and disruptions in this process may trigger maladaptive behaviours underlying anxiety and post-traumatic stress conditions, the most common psychiatric disorders in humans. Despite the abundant literature on defensive processes, the mechanisms regulating APT remain unexplained. Building upon the recently discovered role of cannabinoid type-1 (CB1) receptors in fear-coping behaviour, I will elucidate their involvement in the active-passive balance of defensive responses. Herein, we hypothesize that striatal CB1 receptors are critical switches regulating APT, representing key orchestrators of defensive responses. To tackle this, I will i) expose constitutive, cell type and subcellular-specific CB1 mutant mice to ethologically-relevant paradigms designed to assess APT under comparable conditions of innate or acquired threat exposure, ii) dissect how different striatal CB1 subpopulations control APT and iii) characterize underlying CB1-mediated mechanisms, to provide the first evidence of how CB1 receptors regulate different defensive styles. To achieve this, I will combine my expertise in neuropharmacology, behaviour and machine learning with that of the host lab in cannabinoid biology, circuit manipulation and molecular biology. By leveraging cutting-edge behavioural, viral-genetic and bioinformatic tools and expertise from specialists in the field, DefenCB1 will shed light on new mechanisms regulating defensive responses and provide important insights into how striatal CB1 receptors may be implicated in threat response and psychiatric disorders characterized by maladaptive coping. It will also advance my skills and propel my career as an independent researcher in neuropsychopharmacology.""

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisФранция
UNIVERSITE DE BORDEAUX · BordeauxФранция