Chronic activation of a negative engram induces behavioral and cellular abnormalities.
chemogenetics
engram
hippocampus
learning
memory
mouse
neuroscience
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
11 Jul 2024
11 Jul 2024
Historique:
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
11
7
2024
Statut:
epublish
Résumé
Negative memories engage a brain and body-wide stress response in humans that can alter cognition and behavior. Prolonged stress responses induce maladaptive cellular, circuit, and systems-level changes that can lead to pathological brain states and corresponding disorders in which mood and memory are affected. However, it is unclear if repeated activation of cells processing negative memories induces similar phenotypes in mice. In this study, we used an activity-dependent tagging method to access neuronal ensembles and assess their molecular characteristics. Sequencing memory engrams in mice revealed that positive (male-to-female exposure) and negative (foot shock) cells upregulated genes linked to anti- and pro-inflammatory responses, respectively. To investigate the impact of persistent activation of negative engrams, we chemogenetically activated them in the ventral hippocampus over 3 months and conducted anxiety and memory-related tests. Negative engram activation increased anxiety behaviors in both 6- and 14-month-old mice, reduced spatial working memory in older mice, impaired fear extinction in younger mice, and heightened fear generalization in both age groups. Immunohistochemistry revealed changes in microglial and astrocytic structure and number in the hippocampus. In summary, repeated activation of negative memories induces lasting cellular and behavioral abnormalities in mice, offering insights into the negative effects of chronic negative thinking-like behaviors on human health.
Identifiants
pubmed: 38990919
doi: 10.7554/eLife.96281
pii: 96281
doi:
pii:
Banques de données
GEO
['GSE198731']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : Transformative Award
Pays : United States
Organisme : Air Force Office of Scientific Research
ID : FA9550-21-1-0310
Organisme : Nationai Institutes of Health Early Independence Award
ID : DP5 OD023106-01
Informations de copyright
© 2024, Jellinger, Suthard et al.
Déclaration de conflit d'intérêts
AJ, RS, BY, MS, ER, AC, SL, MS, SR No competing interests declared
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