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The Journal of Neuroscience, September 1, 2000, 20(17):6317-6325
Both Protein Kinase A and Mitogen-Activated Protein Kinase Are
Required in the Amygdala for the Macromolecular Synthesis-Dependent
Late Phase of Long-Term Potentiation
Yan-You
Huang,
Kelsey C.
Martin, and
Eric R.
Kandel
Center for Neurobiology and Behavior, College of Physicians and
Surgeons of Columbia University, New York State Psychiatric Institute,
and Howard Hughes Medical Institute, New York, New York 10032
The lateral amygdala (LA) is thought to be critical for the
specific acquisition of conditioned fear, and the emotionally charged
memories related to fear are thought to require a form of synaptic
plasticity related to long-term potentiation (LTP). Is LTP in the
lateral amygdala enduring, and, if so, does it require gene expression
and the synthesis of new protein? Using brain slices, we have examined
the molecular-signaling pathway of LTP in the cortico-amygdala and the
thalamo-amygdala pathways. We find that a single high-frequency train
of stimuli induces a transient LTP (E-LTP); by contrast, five repeated
high-frequency trains induce an enduring late phase of LTP (L-LTP),
which is dependent on gene expression and on new protein synthesis. In
both pathways the late phase of LTP is mediated by protein kinase A
(PKA) and mitogen-activated protein kinase (MAPK). Application of the
adenylyl cyclase activator forskolin induced L-LTP in both pathways,
and this potentiation is blocked by inhibitors of protein synthesis. The late phase of LTP also is modulated importantly by
-adrenergic agonists. An inhibitor of -adrenergic receptors
blocks L-LTP; conversely, application of a -adrenergic agonist
induces the L-LTP. Immunocytochemical studies show that both repeated
tetanization and application of forskolin stimulate the phosphorylation
of cAMP response element-binding proteins (CREB) in cells of the lateral nucleus of the amygdala. These results suggest that PKA and MAPK are critical for the expression of a persistent phase of LTP
in the lateral amygdala and that this late component requires the
synthesis of new protein and mRNA.
Key words:
amygdala; L-LTP; PKA; MAPK; protein synthesis; CREB
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176317-09$05.00/0
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