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Forebrain‐specific knockout of B‐raf kinase leads to deficits in hippocampal long‐term potentiation, learning, and memory
Author(s) -
Chen Adele P.,
Ohno Masuo,
Giese K. Peter,
Kühn Ralf,
Chen Rachel L.,
Silva Alcino J.
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20703
Subject(s) - long term potentiation , hippocampal formation , neuroscience , term (time) , forebrain , knockout mouse , hippocampus , psychology , biology , physics , biochemistry , central nervous system , receptor , quantum mechanics
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. © 2005 Wiley‐Liss, Inc.