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

Neural inflammation is associated with cognitive decline, especially learning and memory. Tumor necrosis factor ? (TNF?) is a major cytokine generated during neuroinflammation. Previous studies indicated that TNF? impairs hippocampus-dependent memory including contextual fear and spatial memories. However, it is unknown which memory processes are impaired by TNF?. Here, we show that TNF? blocked the retrieval and reconsolidation of contextual fear and spatial memories. Micro-infusion of TNF? 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 TNF? micro-infusion before memory retrieval decreased freezing responses, even at 24 h after retrieval, suggesting that TNF? impairs the reconsolidation of contextual fear memory. Similarly, hippocampal TNF? micro-infusion impaired the retrieval and reconsolidation of spatial memory in the Morris water maze. Consistent with these observations, hippocampal TNF? 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 TNF? negatively regulates the retrieval and reconsolidation of hippocampus-dependent memory.

Automated summary

Neural inflammation, particularly the generation of cytokine TNFα, has been shown to negatively impact cognitive function, especially learning and memory. Experimental results demonstrate that TNFα disrupts the retrieval and reconsolidation processes of contextual fear and spatial memories, providing insight into how neural inflammation affects hippocampus-dependent memory.