Dopamine increases the protein synthesis rate in the hippocampus enabling dopamine-dependent LTP

The reward and novelty-related neuromodulator dopamine has been implicated in protein synthesis-dependent plasticity and is important for long-term memory. However, the direct effects of dopamine on protein synthesis rates and the functional implications of the newly synthesized proteins remain largely unknown. Here, we show that dopamine increases the rate of protein synthesis in hippocampal neurons in CA1, enabling dopamine-dependent long-term potentiation (DA-LTP). Neuronal activity is required for the dopamine-induced increase in protein synthesis, and we found that DA-LTP is mediated by the Ca2+-sensitive adenylate cyclase subunits 1/8 and PKA. Furthermore, dopamine-induced changes in protein synthesis increase GluA1 levels. We found that DA-LTP is absent in GluA1 knockout (KO), and requires calcium-permeable AMPA receptors. Taken together, our results suggest that dopamine, together with neuronal activity, control the synthesis of plasticity-related proteins, enabling DA-LTP.