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

• Published in: Brain, behavior, and immunity Vol. 115; pp. 652 - 666
• Main Authors: Di Castro, Maria Amalia, Garofalo, Stefano, Mormino, Alessandro, Carbonari, Laura, Di Pietro, Erika, De Felice, Eleonora, Catalano, Myriam, Maggi, Laura, Limatola, Cristina
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2024
• Subjects: Animals; Hippocampus; Interleukin-15 - pharmacology; Memory, Episodic; Mice; Neurons; Synaptic Transmission - physiology; IL-15; cytokine-CNS interplay; Behavior; Synaptic transmission; Microglia
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2023.11.015

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-aminobutyricacid (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-HT A 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.