Premium
Neuronal MEK is important for normal fear conditioning in mice
Author(s) -
Shalin Sara C.,
Zirrgiebel Ute,
Honsa Katya J.,
Julien JeanPierre,
Miller Freda D.,
Kaplan David R.,
Sweatt J. David
Publication year - 2004
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.20052
Subject(s) - neuroscience , fear conditioning , mapk/erk pathway , premovement neuronal activity , transgene , kinase , activator (genetics) , cyclin dependent kinase 5 , genetically modified mouse , hippocampus , extracellular , biology , psychology , protein kinase a , microbiology and biotechnology , amygdala , mitogen activated protein kinase kinase , receptor , biochemistry , gene
Abstract The extracellular signal‐regulated kinase (ERK) cascade has received much attention for its possible role in neuronal synaptic plasticity. Although ERK activation has been linked to learning behaviors and activity‐dependent neuronal function, much of the acquired data has relied upon pharmacological agents that suppress ERK function in both neurons and nonneuronal cells. To determine the function of neuronal ERK activity in learning, a new line of transgenic mice was generated wherein dominant‐negative MEK1, the upstream obligate activator of ERK1/2, was expressed by using a neuronal‐specific and pan‐neuronal Tα1 α‐tubulin promoter element. Mice expressing this construct exhibited decreased ERK1/2 activity in the hippocampus and thus were tested for learning impairments. In a battery of control tests, including open field, rotarod, and shock threshold, the transgenic mice displayed no deficits and performed as well as their wild‐type littermate counterparts. However, the mice displayed a significant impairment in contextual fear conditioning compared with the wild‐type littermates. These findings indicate that the MEK1/ERK1/2 cascade within neurons plays an important role in the processes of learning and memory. © 2004 Wiley‐Liss, Inc.