Figure 4.

Noradrenergic β-receptors and PKA strengthen extinction memory through multiple actions in IL. Fear conditioned stimuli evoke NE release in IL, stimulating β-receptors. This, in turn, increases intracellular levels of cAMP, which stimulates activation of PKA. PKA has multiple modes of action. First, PKA increases excitability via phosphorylation of receptors and ion channels, increasing NMDA-mediated calcium influx and promoting synaptic plasticity. Second, PKA interacts with anchoring proteins responsible for AMPA receptor insertion into the membrane. Third, PKA activates downstream targets, including MAPK and the transcription factor CREB, leading to gene transcription and translation necessary for stabilization of extinction memory.