Abstract # 1839 Lentiviral overexpression of interleukin-1β in the hippocampus induces neurogenesis-associated cognitive deficits in adult male Sprague–Dawley rats

Previous studies have demonstrated that acutely elevated levels of the pro-inflammatory cytokine interleukin- 1 β (IL- 1 β in the hippocampus has detrimental effects on some aspects of memory and cognitive function, as well as a negative impact on the proliferation and survival of newly born neurons. The current study aimed to assess whether long-term increased expression of IL- 1 β through lentiviral-mediated overexpression of the protein would alter cognitive performance in hippocampal-dependent tasks including pattern separation, which has been demonstrated to be dependent on hippocampal neurogenesis. To accomplish this, a lentivirus overexpressing IL- 1 β or a control mCherry virus was bilaterally injected into the dorsal dentate gyrus of adult male Sprague–Dawley rats. A battery of behavioural tests were then carried out, including spontaneous alternation in the Y-maze, the location recognition task, pattern separation in a modified location recognition task, and the open field test. IL- 1 β overexpression did not alter spontaneous alternations in the Y-maze test, or location discrimination in the location recognition task. In the pattern separation task, rats overexpressing IL- 1 β in the dorsal dentate gyrus were not able to pattern separate in the small separation condition, but were able to do so with a large separation, suggesting hippocampal neurogenesis-associated dysfunction. Thus, the ability to pattern separate may be more susceptible to the detrimental effects of chronic inflammation than other hippocampal-dependant functions such as working memory and location recognition memory.