The norepinephrine transporter regulates dopamine-dependent synaptic plasticity in the mouse dorsal hippocampus

The rodent dorsal hippocampus is essential for episodic memory consolidation, a process dependent on dopamine D1-like receptor activation. It was previously thought that the ventral tegmental area provided the only supply of dopamine to dorsal hippocampus, but several recent studies have established the locus coeruleus (LC) as a second major source. However, the mechanism for LC-dependent dopamine release has never been explored. Our data identify norepinephrine transporter reversal as one plausible mechanism by demonstrating that transporter blockade can reduce dopamine-dependent long-term potentiation in hippocampal slices. We also suggest that presynaptic NMDA receptors on LC terminals may initiate this norepinephrine transporter reversal. Furthermore, as dopamine and norepinephrine should be co-released from the LC, we show that they act together to enhance synaptic strength. Since LC activity is highly correlated with attentional processes and memory, these experiments provide insight into how selective attention influences memory formation at the synaptic and circuit levels.