| FEAR MEMORY FORMATION INVOLVES p190 RhoGAP AND ROCK
PROTEINS IN AMYGALA |
| R. Lamprecht*; J.E. LeDoux |
| Ctr Neural Sci, New York Univ, New York, NY, USA |
|
Changes in synaptic efficacy underlying
memory are achieved by modulation of molecular activity. We used auditory
fear conditioning, which is known to alter synaptic efficacy in lateral
amygdala (LA), to establish long-term memory. We show that a 190 kDa
tyrosine phosphorylated protein becomes associated with the adapter
molecule GRB2 in LA significantly more in conditioned than in control
rats. The protein was identified to be the Rho-regulatory protein
p190 RhoGAP. RasGAP and Shc were also found to associate with GRB2
significantly more in the conditioned animals. Inhibition in LA of
the p190 RhoGAP-downstream kinase ROCK during fear conditioning impaired
long- but not short-term memory. Thus, the p190 RhoGAP/ROCK pathway,
which regulates the morphology, outgrowth and guidance of dendrites
and axons during neural development, plays a central role, through
a GRB2 mediated molecular complex, in fear memory formation in the
amygdala.
Supported by: This study was supported by NIH grants: MH58911,
MH38774, MH46516, MH00956 and long-term postdoctoral Human Frontier
Science Program fellowship.
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