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Enhanced Fear Memory in Adult Male C57BL/6 Mice Following Low-Dose Isoflurane Exposure During Juvenile Development.

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  • Additional Information
    • Source:
      Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101570837 Publication Model: Print Cited Medium: Internet ISSN: 2162-3279 (Electronic) NLM ISO Abbreviation: Brain Behav Subsets: MEDLINE
    • Publication Information:
      Original Publication: Hoboken, NJ : John Wiley & Sons
    • Subject Terms:
      Fear*/drug effects ; Fear*/physiology ; Isoflurane*/pharmacology ; Isoflurane*/administration & dosage ; Memory*/drug effects ; Memory*/physiology ; Anesthetics, Inhalation*/pharmacology ; Anesthetics, Inhalation*/administration & dosage; Animals ; Male ; Mice, Inbred C57BL ; Mice ; Brain/drug effects ; Animals, Newborn ; Entorhinal Cortex/drug effects ; Proto-Oncogene Proteins c-fos/metabolism
    • Abstract:
      Objective: To elucidate the neural mechanisms through which neonatal exposure to low-dose anesthetic isoflurane (ISO) enhances adult fear memory, specifically examining neural oscillations and activation patterns in the mediodorsal thalamus (MDL), dentate gyrus (DG), anterior cingulate cortex (ACC), and medial entorhinal cortex (MEC).
      Methods: Male C57BL/6 mice received 0.75% ISO or saline injections at postnatal day 7 (P7). At 6 months, contextual fear-memory testing was conducted (Saline + Air: n = 14; Saline + ISO: n = 13). Neural correlates were assessed via in vivo electrophysiology during behavioral tasks and c-Fos immunohistochemistry in the MDL, DG, ACC, and MEC.
      Results: ISO-exposed mice exhibited significantly enhanced fear memory, with >75% displaying freezing as the dominant conditional response (vs. controls). This was accompanied by increased c-Fos+ cell density in the MDL and altered slow gamma oscillation power in fear-processing circuits. Non-freezing responses (e.g., jumping/darting) were reduced in the Saline + ISO group.
      Interpretation: Early low-dose ISO intervention in neonatal mice enhances adult fear memory, potentially through MDL activation and slow gamma oscillation modulation. These findings indicate that low-dose ISO may improve cognitive function by optimizing fear memory consolidation, contrasting with known detrimental effects of high-dose anesthetics on neurodevelopment.
      (© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)
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    • Grant Information:
      JCYJ20230807120302004 Shenzhen Science and Technology Innovation Commission; 202575 United Kingdom WT_ Wellcome Trust; 202501CF070194 Yunnan Fundamental Research Project
    • Contributed Indexing:
      Keywords: fear; isoflurane; safety assessment; sedation; slow gamma oscillations; spatial cognition
    • Accession Number:
      CYS9AKD70P (Isoflurane)
      0 (Anesthetics, Inhalation)
      0 (Proto-Oncogene Proteins c-fos)
    • Publication Date:
      Date Created: 20250930 Date Completed: 20250930 Latest Revision: 20251003
    • Publication Date:
      20251003
    • Accession Number:
      PMC12480919
    • Accession Number:
      10.1002/brb3.70816
    • Accession Number:
      41024616