Both protein kinase a and mitogen-activated protein kinase are required inthe amygdala for the macromolecular synthesis-dependent late phase of long-term potentiation

The lateral amygdala (LA) is thought to be critical for the specific acquis ition of conditioned fear, and the emotionally charged memories related to fear are thought to require a form of synaptic plasticity related to long-t erm potentiation (LTP). Is LTP in the lateral amygdala enduring, and, if so , does it require gene expression and the synthesis of new protein? Using b rain 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 contras t, five repeated high-frequency trains induce an enduring late phase of LTP (L-LTP), which is dependent on gene expression and on new protein synthesi s. In both pathways the late phase of LTP is mediated by protein kinase A ( PKA) and mitogen-activated protein kinase (MAPK). Application of the adenyl yl cyclase activator forskolin induced L-LTP in both pathways, and this pot entiation is blocked by inhibitors of protein synthesis. The late phase of LTP also is modulated importantly by beta-adrenergic agonists. An inhibitor of beta-adrenergic receptors blocks L-LTP; conversely, application of a be ta-adrenergic agonist induces the L-LTP. Immunocytochemical studies show th at both repeated tetanization and application of forskolin stimulate the ph osphorylation of cAMP response element-binding proteins (CREB) in cells of the lateral nucleus of the amygdala. These results suggest that PKA and MAP K are critical for the expression of a persistent phase of LTP in the later al amygdala and that this late component requires the synthesis of new prot ein and mRNA.