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Pro-inflammatory cytokines have been implicated in a wide range of central nervous system (CNS) disorders, including trauma, ischemia, multiple sclerosis and Alzheimer s disease. Tumour necrosis factor- (TNF- ) and interleukin-18 (IL-18), both pro-inflammatory cytokines, have previously been shown to attenuate long-term potentiation (LTP), a proposed model for learning and memory. This study investigated the mechanisms underlying the TNF- and IL-18 mediated inhibition of LTP. Initial experiments consolidate evidence on inducing LTP in the dentate gyrus of the hippocampus. Subsequent experiments consolidate evidence that TNF- and IL-18 can impair LTP in the dentate gyrus.