| Ca2+/CALMODULIN DEPENDENT PROTEIN KINASE
II IS REQUIRED FOR FEAR MEMORY FORMATION IN THE LATERAL AMYGDALA
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| S.M. Rodrigues*; C.R. Farb; J.E. LeDoux; G.E.
Schafe |
| Center for Neural Science, New York University, New York,
NY, USA |
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Ca2+/calmodulin dependent protein
kinase II(CaMKII) is a multifunctional enzyme that is critical for
synaptic plasticity and memory formation. In this study, we used neuroanatomical,
Western immunoblotting, and behavioral methods to examine the role
of CaMKII in the lateral nucleus of the amygdala (LA), a critical
site of plasticity in fear conditioning. First, we used immunohistochemistry
to evaluate the cellular and subcellular localization of the active
(phosphorylated) form of the enzyme (pCAMKII) in the LA. By light
microscopy, pCAMKII-immunoreactivity appeared to be most robust in
the dorsal LA, and was expressed in cytoplasm, proximal dendrites,
and punctate processes. At the EM level, pCAMKII was localized to
perikarya with the morphological characteristics of projection cells,
large and small dendritic shafts, spines, and axon terminals. Next,
we used Western immunoblotting to measure changes in pCaMKII in the
LA after fear conditioning. Preliminary results suggest an increase
in pCaMKII levels in the LA of conditioned animals relative to controls.
This increase peaked at 15 m and persisted for at least 3 h after
conditioning, and it was not accounted for by changes in total CaMKII
levels. Finally, we gave rats pretraining intra-LA infusions of the
CaMKII antagonist, KN-62. KN-62 produced a dose-dependent disruption
of the acquisition of tone and contextual fear memory at both 1 h
and 24 h after conditioning. In contrast, KN-62 had no significant
effect on the expression of conditioned fear. Together, these findings
suggest that CaMKII is an important component of fear memory acquisition
in the LA.
Supported by: MH38774, MH00956, & MH46516
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