Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity

Hippocampus. 2003;13(7):826-34. doi: 10.1002/hipo.10135.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Psychological / physiology
  • Electric Stimulation
  • Fear / physiology
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Interleukin-1 / metabolism*
  • Long-Term Potentiation / genetics
  • Male
  • Maze Learning / physiology
  • Memory Disorders / genetics
  • Memory Disorders / metabolism*
  • Memory Disorders / physiopathology
  • Mice
  • Mice, Knockout
  • Neural Inhibition / genetics
  • Neuronal Plasticity / genetics*
  • Reaction Time / genetics
  • Receptors, Interleukin-1 / deficiency*
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 Type I
  • Signal Transduction / genetics

Substances

  • Interleukin-1
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I