Descrizione del progetto
Comprendere il ruolo del recettore CB1 striatale nelle strategie difensive
Gli organismi utilizzano strategie difensive attive (fuga) o passive (bloccarsi), a seconda della minaccia che devono affrontare, un equilibrio definito come Active-Passive Trade-off (APT). Le interruzioni dell’APT possono portare a comportamenti disadattivi, contribuendo all’ansia e allo stress post-traumatico. Tuttavia, nonostante le numerose ricerche, i meccanismi che regolano l’APT rimangono elusivi. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto DefenCB1 esplora il ruolo dei recettori CB1 nel comportamento di fronte alla paura e il loro impatto sull’equilibrio tra risposte difensive attive e passive. Si ipotizza che i recettori CB1 nel corpo striato svolgano un ruolo cruciale nell’orchestrare le reazioni di difesa. Studierà come le varie sottopopolazioni di recettori CB1 nel corpo striato influenzino gli stili difensivi e fornirà informazioni sui meccanismi che regolano le risposte difensive.
Obiettivo
"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."
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Invito a presentare proposte
(si apre in una nuova finestra) HORIZON-MSCA-2023-PF-01
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HORIZON-TMA-MSCA-PF-EF -Coordinatore
75654 Paris
Francia