Balanced dopamine signaling for healthy learning and memory

In the mammalian brain, reward learning and memory depend on dopamine (DA) signaling. One type of signal, defined by a short absence of DA (0.5–2 s) called the “DA dip”, triggers long-term memory formation. To understand the underlying mechanism of the DA dip the researchers previously developed a computational model of DA signaling (Urakubo et al., 2020; PLoS Comput Biol 16(7): e1008078). In the current study, Urakubo et al. examined how DA dips are processed through a biochemical signaling network to generate long-term memory. Computer simulations and theoretical analyses showed that the DA dip signal is processed only if there is a balance in the levels of two key molecules, D2R and RGS (Fig 1A,1B). This balance is achieved during healthy development, whereas an imbalance between D2R and RGS levels is evident in patients with schizophrenia and DYT1 dystonia (Fig 1B), and could manifest in abnormal long-term memory. In computational analyses, the D2R–RGS imbalance hampered DA dip detectability, disturbed long-term memory formation, and resulted in selective symptoms of schizophrenia and dystonia. Thus, the balance between D2R and RGS appears to be a key biochemical control point for normal learning and memory in the brain.