IL-2/15 receptor-beta gene deletion alters neurobehavioral performance.
The common IL-2/15 receptor-beta (IL-2/15Rbeta) is an essential signaling subunit that is shared exclusively by IL-2 and IL-15, and is enriched in the hippocampal formation and related limbic regions. We have previously shown that mice lacking IL-2 exhibit alterations in hippocampal-dependent learning, sensorimotor gating and accompanying reductions in hippocampal infrapyramidal mossy neuronal fiber length. Although the effects of exogenous IL-2 on various aspects of forebrain neuronal function are well documented, it is unclear whether IL-15 has neuromodulatory actions. Here we sought to test the hypothesis that the combined loss of the ability of IL-2 and IL-15 to signal through IL-2/15Rbeta in the brain would influence neurobehavioral performance, in particular spatial learning and memory performance. To test this hypothesis, we compared several different domains of behavior in mice that had one or both IL-2/15Rbeta gene alleles deleted. Compared with C57BL/6-IL-2/15Rbeta+/+ wild-type and C57BL/6-IL-2/15Rbeta+/- heterozygote littermates, C57BL/6-IL-2/15Rbeta-/- knockout mice exhibited a deficit in prepulse inhibition of the acoustic startle reflex (PPI). The IL-2/15Rbeta knockout mice also showed significant reductions in acoustic startle reactivity, and modest differences in behavior in the elevated plus-maze test indicative of reduced levels of fearfulness in response to novelty. The IL-2/15Rbeta knockout mice did not differ in locomotor activity in either the plus-maze or the Morris water-maze, and contrary to our working hypothesis, they did not differ in spatial learning or memory performance in the water-maze. Further studies are required to determine if these behavioral alterations may be attributable to factors such as the loss of the ability of IL-15 and/or IL-2 to modulate limbic neurons, autoimmunity or genetic factors associated with IL-2/15Rbeta gene deletion.
Petitto
John M
JM
McKnight Brain Institute, Departments of Psychiatry, Neuroscience, and Pharmacology, University of Florida College of Medicine, Gainesville, FL 32610-0256, USA. jpetitto@psych.med.ufl.edu
Huang
Zhi
Z
Hartemink
David A
DA
Beck
Ray
R
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D017353:Gene Deletion; D053646:Interleukin-2 Receptor beta Subunit; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009424:Nervous System Physiological Phenomena; D009433:Neural Inhibition / Q000502:physiology; D018123:Receptors, Interleukin / Q000235:genetics*; D013216:Reflex, Startle / Q000502:physiology; D013550:Swimming
C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D018123:Receptors, Interleukin