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PMID: 12441060 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex.

Neuron ·Vol. 36 ·No. 4 ·2002-11-14 ·Pages 727-38

Lamprecht R, Farb CR, LeDoux JE

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport Amygdala/metabolism,ultrastructure Animals Conditioning, Psychological/physiology DNA-Binding Proteins Enzyme Inhibitors/pharmacology Fear/physiology GRB2 Adaptor Protein Guanine Nucleotide Exchange Factors/metabolism Immunohistochemistry Intracellular Signaling Peptides and Proteins Male Memory/physiology Memory, Short-Term/drug effects,physiology Microscopy, Electron Neurons/metabolism,ultrastructure Nuclear Proteins/metabolism Phosphorylation Protein Serine-Threonine Kinases/metabolism Proteins/metabolism Rats Rats, Sprague-Dawley Repressor Proteins Shc Signaling Adaptor Proteins Src Homology 2 Domain-Containing, Transforming Protein 1 Tyrosine/metabolism ras GTPase-Activating Proteins/metabolism rho-Associated Kinases
Chemicals
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport Arhgap35 protein, rat DNA-Binding Proteins Enzyme Inhibitors GRB2 Adaptor Protein Grb2 protein, rat Guanine Nucleotide Exchange Factors Intracellular Signaling Peptides and Proteins Nuclear Proteins Proteins Repressor Proteins Shc Signaling Adaptor Proteins Shc1 protein, rat Src Homology 2 Domain-Containing, Transforming Protein 1 ras GTPase-Activating Proteins Tyrosine Protein Serine-Threonine Kinases rho-Associated Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lamprecht Raphael
W.M. Keck Foundation Laboratory for Neurobiology, Center for Neural Science, New York University, New York, NY 10003, USA.
Farb Claudia R
LeDoux Joseph E
Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
DOI
10.1016/s0896-6273(02)01047-4
Published
2002-11-14
Pages
727-38
Language
English
Region
United States
NLM ID
8809320
Subset
IM
Grants
NIMH NIH HHS · MH00956 · United States
NIMH NIH HHS · MH38774 · United States
NIMH NIH HHS · MH46516 · United States
NIMH NIH HHS · MH58911 · United States
External Links
PubMed source DOI: 10.1016/s0896-6273(02)01047-4 View journal details
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