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

Item Type:Article
Title:Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory
Creators Name:Chen, A.P. and Ohno, M. and Giese, K.P. and Kuehn, R. and Chen, R.L. and Silva, A.J.
Abstract: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.
Keywords:MEK-ERK, Ras, Cre-LoxP, Conditional Knockout, Water Maze, Contextual Discrimination, Fear Conditioning, Conditioned Taste Aversion, Animals, Mice
Source:Journal of Neuroscience Research
ISSN:0360-4012
Publisher:Wiley (U.S.A.)
Volume:83
Number:1
Page Range:28-38
Date:January 2006
Official Publication:https://doi.org/10.1002/jnr.20703
PubMed:View item in PubMed

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