Tumor necrosis factor α negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory

Shohei Takahashi, Hotaka Fukushima, Zhiqian Yu, Hiroaki Tomita, Satoshi Kida

Research output: Contribution to journalArticlepeer-review

Abstract

Neural inflammation is associated with cognitive decline, especially learning and memory. Tumor necrosis factor α (TNFα) is a major cytokine generated during neuroinflammation. Previous studies indicated that TNFα impairs hippocampus-dependent memory including contextual fear and spatial memories. However, it is unknown which memory processes are impaired by TNFα. Here, we show that TNFα blocked the retrieval and reconsolidation of contextual fear and spatial memories. Micro-infusion of TNFα into the dorsal hippocampus at 6–18 h before retrieval impaired the retrieval of contextual fear memory, although micro-infusion before contextual fear conditioning had no effect on memory formation. Interestingly, hippocampal TNFα micro-infusion before memory retrieval decreased freezing responses, even at 24 h after retrieval, suggesting that TNFα impairs the reconsolidation of contextual fear memory. Similarly, hippocampal TNFα micro-infusion impaired the retrieval and reconsolidation of spatial memory in the Morris water maze. Consistent with these observations, hippocampal TNFα micro-infusion before retrieval blocked the induction of c-fos expression in the hippocampus, which is a marker of neural activation, in response to the retrieval of contextual fear memory. Collectively, our findings indicate that TNFα negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory.

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalBrain, Behavior, and Immunity
Volume94
DOIs
Publication statusPublished - 2021 May
Externally publishedYes

Keywords

  • Contextual fear memory
  • Hippocampus
  • Memory reconsolidation
  • Memory retrieval
  • Spatial memory
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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