IL-4R α 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.

Automated summary

This study demonstrates that mice lacking interleukin-4 receptor alpha can successfully learn spatial tasks while their reference memory is impaired. The absence of interleukin-4 receptor alpha leads to an increase in the proportions of CD11b+ myeloid cells in the hippocampus and thalamus, with alterations in interferon gamma and brain-derived neurotrophic factor expression. These findings suggest that interleukin-4 receptor alpha is essential for cognitive performance and training-induced changes in immune mediators may modulate memory encoding and consolidation.