Interleukin-15 alters hippocampal synaptic transmission and impairs episodic memory formation in mice

Cytokines are potent immunomodulators exerting pleiotropic effects in the central nervous system (CNS). They influence neuronal functions and circuit activities with effects on memory processes and behaviors. Here, we unravel a neuromodulatory activity of interleukin-15 (IL-15) in mouse brain. Acute exposure of hippocampal slices to IL-15 enhances gamma-aminobutyric acid (GABA) release and reduces glutamatergic currents, while chronic treatment with IL-15 increases the frequency of hippocampal miniature inhibitory synaptic transmission and impairs memory formation in the novel object recognition (NOR) test. Moreover, we describe that serotonin is involved in mediating the hippocampal effects of IL-15, because a selective 5-HT3A receptor antagonist prevents the effects on inhibitory neurotransmission and ameliorates mice performance in the NOR test. These findings provide new insights into the modulatory activities of cytokines in the CNS, with implications on behavior.

Automated summary

Cytokines, such as interleukin-15 (IL-15), play important roles in modulating the central nervous system (CNS). In this study, the authors found that exposure to IL-15 enhances GABA release and reduces glutamatergic currents in hippocampal slices. Chronic treatment with IL-15 has negative effects on memory formation. Serotonin is involved in mediating these effects, as a selective 5-HT3A receptor antagonist prevents the effects on inhibitory neurotransmission and improves performance in a memory test.