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Selection of active defensive behaviors relies on extended amygdala dopamine D2 receptors

Laia CastelliD, Valentine Le GalliD, Laura CutandoiD, Emma PuighermanaliD, Daniel JercogiD, Pauline TarotiD, Adrien TassouiD, Anne-Gabrielle HarrusiD, Marcelo RubinsteiniD, Régis NouvianiD, Cyril RivatiD, Cyril HerryiD, Emmanuel ValjentiD

PDFDOI

Abstract

The ability to efficiently switch from one defensive strategy to another maximizes an animals chance of survival. Here, we demonstrate that the selection of active defensive behaviors requires the coordinated activation of dopamine D2 receptor (D2R) signaling within the central extended amygdala (EA) comprising the nucleus accumbens, the oval bed nucleus stria terminals and the central amygdala. We find that discriminative learning between predictive and non-predictive threat auditory stimuli is unaltered in mice carrying a temporally-controlled deletion of D2R within output neurons of the EA. In contrast, intact EA D2R signaling is required for active avoidance learning and innate flight responses triggered by a visual threat stimulus (looming). Consequently, conditional D2R knockout mice biased defensive responses toward passive defensive strategies. Altogether, these findings identify EA D2R signaling as an important mechanism by which DA regulates the switch from passive to active defensive behaviors, regardless whether of learned or innate threat.

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Laia Castell, Angelina Rogliardo, Tinaïg Le Borgne+17 more·bioRxiv·Nov 12, 2024· 3 citations