A double dissociation between the effects of sub-pyrogenic systemic inflammation and hippocampal lesions on learning

Immune system activation has been found to affect the function of the hippocampus. Sub-pyrogenic systemic inflammation impairs performance of species-typical behaviours that are also disrupted by hippocampal lesions in rodents. In a series of experiments the effect of a low, sub-pyrogenic dose of lipopolysaccharide (LPS) on hippocampus-dependent learning and memory was tested. LPS failed to impair hippocampus-dependent spatial reference memory and working memory. However, LPS affected learning a simple side-discrimination task in which an arm of a T-maze was rewarded (correct arm), and the other arm was never rewarded (incorrect arm). Whereas LPS actually enhanced performance when reward was available on every trial in the correct arm, LPS impaired learning when the correct arm was rewarded on 50% of trials. Hippocampal lesions did not impair either the continuous or partial reinforcement versions of the task. These results demonstrate that a low, sub-pyrogenic dose of LPS can impair cognitive function, but can, depending on the demands of the task, also facilitate learning. However, the double dissociation between the effects of LPS and hippocampal lesions demonstrate that sub-pyrogenic inflammation does not affect learning by disrupting hippocampal function.