Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex.
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.
Lamprecht
Raphael
R
W.M. Keck Foundation Laboratory for Neurobiology, Center for Neural Science, New York University, New York, NY 10003, USA.
Farb
Claudia R
CR
LeDoux
Joseph E
JE
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000679:Amygdala / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D051380:GRB2 Adaptor Protein; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D008854:Microscopy, Electron; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D054460:rho-Associated Kinases
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C513040:Arhgap35 protein, rat; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012097:Repressor Proteins; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases