title: Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory.
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.
authors.affiliation: Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, 90095-1761, USA.
authors.forename: Adele P
authors.initials: AP
authors.lastname: Chen
authors.forename: Masuo
authors.initials: M
authors.lastname: Ohno
authors.forename: K Peter
authors.initials: KP
authors.lastname: Giese
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Chen
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D004192:Discrimination, Psychological / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004594:Electrophysiology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000502:physiology*; D013649:Taste / Q000502:physiology
chemical_list: D048493:Proto-Oncogene Proteins B-raf