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Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory.

Raf kinases are downstream effectors of Ras and upstream activators of the MEK-ERK cascade. Ras and MEK-ERK signaling play roles in learning and memory (L&M) and neural plasticity, but the roles of Raf kinases in L&M and plasticity are unclear. Among Raf isoforms, B-raf is preferentially expressed in the brain. To determine whether B-raf has a role in synaptic plasticity and L&M, we used the Cre-LoxP gene targeting system to derive forebrain excitatory neuron B-raf knockout mice. This conditional knockout resulted in deficits in ERK activation and hippocampal long-term potentiation (LTP) and impairments in hippocampus-dependent L&M, including spatial learning and contextual discrimination. Despite the widespread expression of B-raf, this mutation did not disrupt other forms of L&M, such as cued fear conditioning and conditioned taste aversion. Our findings demonstrate that B-raf plays a role in hippocampal ERK activation, synaptic plasticity, and L&M.

Pubmed ID: 16342120


  • Chen AP
  • Ohno M
  • Giese KP
  • Kühn R
  • Chen RL
  • Silva AJ


Journal of neuroscience research

Publication Data

January 27, 2006

Associated Grants

  • Agency: NINDS NIH HHS, Id: R01NS38480

Mesh Terms

  • Animals
  • Avoidance Learning
  • Behavior, Animal
  • Blotting, Western
  • Discrimination (Psychology)
  • Down-Regulation
  • Electrophysiology
  • Fear
  • Hippocampus
  • Immunohistochemistry
  • Learning
  • Long-Term Potentiation
  • Maze Learning
  • Memory
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins B-raf
  • Taste