Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity.
The cytokine interleukin-1 (IL-1) is produced by peripheral immune cells as well as glia and neurons within the brain; it plays a major role in immune to brain communication and in modulation of neural, neuroendocrine, and behavioral systems during illness. Although previous studies demonstrated that excess levels of IL-1 impaired memory processes and neural plasticity, it has been suggested that physiological levels of IL-1 are involved in hippocampal-dependent memory and long-term potentiation (LTP). To examine this hypothesis, we studied IL-1 receptor type I knockout (IL-1rKO) mice in several paradigms of memory function and hippocampal plasticity. In the spatial version of the water maze test, IL-1rKO mice displayed significantly longer latency to reach a hidden platform, compared with wild-type controls. Furthermore, IL-1rKO exhibited diminished contextual fear conditioning. In contrast, IL-1rKO mice were similar to control animals in hippocampal-independent memory tasks; i.e., their performance in the visually guided task of the water maze and the auditory-cued fear conditioning was normal. Electrophysiologically, anesthetized IL-1rKO mice exhibited enhanced paired-pulse inhibition in response to perforant path stimulation and no LTP in the dentate gyrus. In vitro, decreased paired-pulse responses, as well as a complete absence of LTP, were observed in the CA1 region of hippocampal slices taken from IL-1rKO mice compared with WT controls. These results suggest that IL-1 contributes to the regulation of memory processes as well as short- and long-term plasticity within the hippocampus. These findings have important implications to several conditions in humans, which are associated with long-term defects in IL-1 signaling, such as mutations in the IL-1 receptor accessory protein-like gene, which are involved in a frequent form of X-linked mental retardation.
Avital
Avi
A
Department of Psychology, Haifa University, Haifa, Israel.
Goshen
Inbal
I
Kamsler
Ariel
A
Segal
Menahem
M
Iverfeldt
Kerstin
K
Richter-Levin
Gal
G
Yirmiya
Raz
R
D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D004558:Electric Stimulation; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D007375:Interleukin-1 / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics*; D011930:Reaction Time / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics; D053573:Receptors, Interleukin-1 Type I; D015398:Signal Transduction / Q000235:genetics
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I