Effects of repetitive training on learning and memory performance of TLR2 KO mice

Behav Brain Res. 2022 May 24:426:113836. doi: 10.1016/j.bbr.2022.113836. Epub 2022 Mar 9.


Current antipsychotics have limited effects on the cognitive deficits of schizophrenia patients, therefore, cognitive remediation has been applied to schizophrenia patients to ameliorate cognitive dysfunction. However, the neurobiological mechanisms of cognitive training programs have not been well studied because established animal models are not suitable or because repetitive training has not been introduced in such animal models. In the present study, we employed Toll-like receptor 2 knockout (TLR2 KO) mouse as a schizophrenia mouse model and evaluated the effects of repetitive training as cognitive remediation therapy for schizophrenia. TLR2 KO mice could fully learn the Barnes maze paradigm through repetitive training to improve memory retrieval and reversal learning ability, although the learning speed was slower than that of wild-type (WT) animals. In addition, highly repetitive training activated the neuronal cells in the prefrontal cortex, hippocampal CA3 and hippocampal DG regions of TLR2 KO mice, similar to WT mice. These results indicated that TLR2 KO mouse would be a useful tool for studying the neurobiological mechanisms of cognitive remediation in schizophrenia.

Keywords: Barnes maze test; Cognitive function; Cognitive remediation; Schizophrenia; TLR2 KO mouse; c-Fos.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognition*
  • Hippocampus / metabolism
  • Humans
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reversal Learning / physiology
  • Toll-Like Receptor 2* / genetics
  • Toll-Like Receptor 2* / metabolism


  • TLR2 protein, human
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2