PT - JOURNAL ARTICLE AU - Camille de Almeida AU - Nida Chabbah AU - Camille Eyraud AU - Caroline Fasano AU - Véronique Bernard AU - Nicolas Pietrancosta AU - Véronique Fabre AU - Salah El Mestikawy AU - Stephanie Daumas TI - Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice AID - 10.1523/ENEURO.0304-22.2023 DP - 2023 Feb 01 TA - eneuro PG - ENEURO.0304-22.2023 VI - 10 IP - 2 4099 - http://www.eneuro.org/content/10/2/ENEURO.0304-22.2023.short 4100 - http://www.eneuro.org/content/10/2/ENEURO.0304-22.2023.full SO - eNeuro2023 Feb 01; 10 AB - Fear is an emotional mechanism that helps to cope with potential hazards. However, when fear is generalized, it becomes maladaptive and represents a core symptom of posttraumatic stress disorder (PTSD). Converging lines of research show that dysfunction of glutamatergic neurotransmission is a cardinal feature of trauma and stress related disorders such as PTSD. However, the involvement of glutamatergic co-transmission in fear is less well understood. Glutamate is accumulated into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The atypical subtype, VGLUT3, is responsible for the co-transmission of glutamate with acetylcholine, serotonin, or GABA. To understand the involvement of VGLUT3-dependent co-transmission in aversive memories, we used a Pavlovian fear conditioning paradigm in VGLUT3–/– mice. Our results revealed a higher contextual fear memory in these mice, despite a facilitation of extinction. In addition, the absence of VGLUT3 leads to fear generalization, probably because of a pattern separation deficit. Our study suggests that the VGLUT3 network plays a crucial role in regulating emotional memories. Hence, VGLUT3 is a key player in the processing of aversive memories and therefore a potential therapeutic target in stress-related disorders.