TY - JOUR
T1 - Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex
AU - Lamprecht, Raphael
AU - Farb, Claudia R.
AU - LeDoux, Joseph E.
N1 - Funding Information:
We thank Keren Paz for excellent advice and discussions. This work was supported by NIH grants MH58911, MH46516, MH38774, MH00956, and a Human Frontier Science Program postdoctoral fellowship.
PY - 2002/11/14
Y1 - 2002/11/14
N2 - We used fear conditioning, which is known to alter synaptic efficacy in lateral amygdala (LA), to study molecular mechanisms underlying long-term memory. Following fear conditioning, the tyrosine phosphorylated protein p190 RhoGAP becomes associated with GRB2 in LA significantly more in conditioned than in control rats. RasGAP and Shc were also found to associate with GRB2 in LA significantly more in the conditioned animals. Inhibition of the p190 RhoGAP-downstream kinase ROCK in LA during fear conditioning impaired long- but not short-term memory. Thus, the p190 RhoGAP/ROCK pathway, which regulates the morphology of dendrites and axons during neural development, plays a central role, through a GRB2-mediated molecular complex, in fear memory formation in the lateral amygdala.
AB - We used fear conditioning, which is known to alter synaptic efficacy in lateral amygdala (LA), to study molecular mechanisms underlying long-term memory. Following fear conditioning, the tyrosine phosphorylated protein p190 RhoGAP becomes associated with GRB2 in LA significantly more in conditioned than in control rats. RasGAP and Shc were also found to associate with GRB2 in LA significantly more in the conditioned animals. Inhibition of the p190 RhoGAP-downstream kinase ROCK in LA during fear conditioning impaired long- but not short-term memory. Thus, the p190 RhoGAP/ROCK pathway, which regulates the morphology of dendrites and axons during neural development, plays a central role, through a GRB2-mediated molecular complex, in fear memory formation in the lateral amygdala.
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U2 - 10.1016/S0896-6273(02)01047-4
DO - 10.1016/S0896-6273(02)01047-4
M3 - Article
C2 - 12441060
AN - SCOPUS:0037079063
SN - 0896-6273
VL - 36
SP - 727
EP - 738
JO - Neuron
JF - Neuron
IS - 4
ER -