IL-4Rα deletion disrupts psychomotor performance and reference memory in mice while sparing behavioural phenotype associated with spatial learning

Contribution of immune mediators, interleukin-4 and interferon gamma to cognitive functioning is receiving increasing attention. However, the fundamental question about how heterodimeric interleukin-4 receptor alpha– and interferon gamma– producing myeloid cells converge to influence hippocampal–dependent spatial memory tasks through immunomodulation of multisensory inputs from other brain areas remains unexplored. Here, we show that mice lacking interleukin-4 receptor alpha are able to successfully learn spatial tasks, while reference memory is impaired. Moreover, the absence of interleukin-4 receptor alpha leads to simultaneous increase in proportions of CD11b + myeloid cells in the hippocampus and thalamus, but not the brainstem during acquisition. Interleukin-4 receptor alpha deletion significantly decreased expression of myeloid cell–derived interferon gamma in the thalamus during the acquisition phase and simultaneously increased brain-derived neurotrophic factor production in the thalamus and brainstem of trained mice. We provide evidence that interleukin-4 receptor alpha is essential for cognitive performance while training–induced alterations in interferon gamma activity and brain-derived neurotrophic factor signalling may contribute to neuromodulation of learned tasks and consequently affect systems–level memory encoding and consolidation.