Descripción del proyecto
Comprensión del papel del receptor CB1 del cuerpo estriado en las estrategias defensivas
Los organismos utilizan estrategias defensivas activas (huida) o pasivas (inmovilización), en función de la amenaza a la que se enfrentan, un equilibrio que se denomina «equilibrio activo-pasivo» (APT, por sus siglas en inglés). Las alteraciones del APT pueden dar lugar a comportamientos inadaptados, que contribuyen a la ansiedad y al estrés postraumático. Sin embargo, a pesar de las numerosas investigaciones realizadas, los mecanismos que regulan el APT siguen siendo difíciles de determinar. Con el apoyo de las Acciones Marie Skłodowska-Curie, el equipo del proyecto DefenCB1 explora el papel de los receptores CB1 en el comportamiento al afrontar el miedo y su impacto en el equilibrio entre las respuestas defensivas activas y pasivas. Se plantea la hipótesis de que los receptores CB1 del cuerpo estriado desempeñan un papel crucial en la orquestación de las reacciones defensivas. Estudiará cómo influyen las distintas subpoblaciones de receptores CB1 en el cuerpo estriado en los estilos defensivos y proporcionará información sobre los mecanismos que rigen las respuestas defensivas.
Objetivo
"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."
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinador
75654 Paris
Francia