The amygdala NT3-TrkC pathway underlies inter-individual differences in fear extinction and related synaptic plasticity

• DOI: 10.1038/s41380-024-02412-z
• Publication Date: 2024-01-17T07:02:55Z
• Authors: Gianluca Masella; Francisca Silva; Elisa Corti; Garikoitz Azkona; Maria Francisca M...; Ângelo R. Tomé; Samira G. Ferreira; Rodrigo A. Cunha; Carlos B. Duarte; Mónica Santos
• Keywords: Extinction (optical mineralogy)

Fear-related pathologies are among the most prevalent psychiatric conditions, having inappropriate learned fear and resistance to extinction as cardinal features. Exposure therapy represents a promising therapeutic approach, efficiency of which depends on inter-individual variation in learning, neurobiological basis is unknown. We characterized model whereby fear-conditioned mice were categorized (EXT)-success or EXT-failure, according their inherent ability extinguish fear. In lateral amygdala, GluN2A-containing NMDAR required for LTP stabilization memories, while GluN2B-containing LTD extinction. EXT-success showed attenuated LTP, strong higher levels synaptic GluN2B, EXT-failure no GluN2A. Neurotrophin 3 (NT3) infusion amygdala was sufficient rescue deficits mice. Mechanistically, activation tropomyosin receptor kinase C (TrkC) with NT3 slices GluN2B-dependent manner. Conversely, blocking endogenous NT3-TrkC signaling TrkC-Fc chimera strengthened LTP. Our data support key role system differences rodents, through modulation amygdalar composition plasticity.