Neonatal exposure to bacteria in rats leads to memory impairment following an immune challenge in adulthood. The proposed research will explore this phenomenon by examining 1) the role of the pro- inflammatory cytokine interleukin [IL]-1beta, 2) the mechanism(s) underlying cytokine-induced memory impairment, and 3) the generality of the phenomenon. To test the hypothesis that IL-1 produced in response to an immune challenge (LPS) in adulthood impairs memory, an IL-1 synthesis inhibitor will be administered prior to the learning experience and subsequent LPS, which normally impairs memory in neonatally-infected rats. To determine the mechanism(s) underlying cytokine-induced memory impairment, adult rats treated as neonates with bacteria or PBS will be injected with LPS or saline, and cytokine and glial cell marker gene expression will be measured in the hippocampus. LTP and BDNF expression will be measured in the hippocampus following LPS. To determine the generality of these effects, rats will be infected prenatally or neonatally with bacteria or virus, and behavioral consequences will be measured in adults. The duration of memory impairment will also be measured, and a number of memory paradigms will be tested.
