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Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice

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 cardin...

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Autores principales: de Almeida, Camille, Chabbah, Nida, Eyraud, Camille, Fasano, Caroline, Bernard, Véronique, Pietrancosta, Nicolas, Fabre, Véronique, El Mestikawy, Salah, Daumas, Stephanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953049/
https://www.ncbi.nlm.nih.gov/pubmed/36720646
http://dx.doi.org/10.1523/ENEURO.0304-22.2023
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author de Almeida, Camille
Chabbah, Nida
Eyraud, Camille
Fasano, Caroline
Bernard, Véronique
Pietrancosta, Nicolas
Fabre, Véronique
El Mestikawy, Salah
Daumas, Stephanie
author_facet de Almeida, Camille
Chabbah, Nida
Eyraud, Camille
Fasano, Caroline
Bernard, Véronique
Pietrancosta, Nicolas
Fabre, Véronique
El Mestikawy, Salah
Daumas, Stephanie
author_sort de Almeida, Camille
collection PubMed
description 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.
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spelling pubmed-99530492023-02-25 Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice de Almeida, Camille Chabbah, Nida Eyraud, Camille Fasano, Caroline Bernard, Véronique Pietrancosta, Nicolas Fabre, Véronique El Mestikawy, Salah Daumas, Stephanie eNeuro Research Article: New Research 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. Society for Neuroscience 2023-02-22 /pmc/articles/PMC9953049/ /pubmed/36720646 http://dx.doi.org/10.1523/ENEURO.0304-22.2023 Text en Copyright © 2023 de Almeida et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article: New Research
de Almeida, Camille
Chabbah, Nida
Eyraud, Camille
Fasano, Caroline
Bernard, Véronique
Pietrancosta, Nicolas
Fabre, Véronique
El Mestikawy, Salah
Daumas, Stephanie
Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice
title Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice
title_full Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice
title_fullStr Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice
title_full_unstemmed Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice
title_short Absence of VGLUT3 Expression Leads to Impaired Fear Memory in Mice
title_sort absence of vglut3 expression leads to impaired fear memory in mice
topic Research Article: New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953049/
https://www.ncbi.nlm.nih.gov/pubmed/36720646
http://dx.doi.org/10.1523/ENEURO.0304-22.2023
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