Pavlovian Fear Conditioning Regulates Thr286Autophosphorylation of Ca2+/Calmodulin-Dependent Protein Kinase II at Lateral Amygdala Synapses

Journal of Neuroscience - Tập 24 Số 13 - Trang 3281-3288 - 2004
Sarina M. Rodrigues1, Claudia R. Farb2, Elizabeth P. Bauer2, Joseph E. LeDoux3, Glenn E. Schafe4
1W.M. Keck Foundation, Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003, USA
2New York University
3Neural Science
4Yale University

Tóm tắt

Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role in synaptic plasticity and memory formation in a variety of learning systems and species. The present experiments examined the role of CaMKII in the circuitry underlying pavlovian fear conditioning. First, we reveal by immunocytochemical and tract-tracing methods that αCaMKII is postsynaptic to auditory thalamic inputs and colocalized with the NR2B subunit of the NMDA receptor. Furthermore, we show that fear conditioning results in an increase of the autophosphorylated (active) form of αCaMKII in lateral amygdala (LA) spines. Next, we demonstrate that intra-amygdala infusion of a CaMK inhibitor, 1-[NO-bis-1,5-isoquinolinesulfonyl]-N-methyl-l-tyrosyl-4-phenylpiperazine, KN-62, dose-dependently impairs the acquisition, but not the expression, of auditory and contextual fear conditioning. Finally, in electrophysiological experiments, we demonstrate that an NMDA receptor-dependent form of long-term potentiation at thalamic input synapses to the LA is impaired by bath application of KN-62in vitro. Together, the results of these experiments provide the first comprehensive view of the role of CaMKII in the amygdala during fear conditioning.

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Thông tin xuất bản

Journal of Neuroscience

Tập 24 Số 13

3281-3288

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