Dopamine · Grey Matter

Dopamine is a neuromodulator made by a small group of midbrain neurons that broadcasts, to the striatum and the frontal cortex, whether things are going better or worse than expected, and that signal drives learning from reward, the vigour of movement and motivation.

Dopamine. Dopamine is a neuromodulator made by a small group of midbrain neurons that broadcasts, to the striatum and the frontal cortex, whether things are going better or worse than expected, and that signal drives learning from reward, the vigour of movement and motivation.

The cells sit in the substantia nigra, projecting mainly to the dorsal striatum (movement and habits), and in the ventral tegmental area, projecting to the ventral striatum (nucleus accumbens) and prefrontal cortex (reward, motivation, working memory). Dopamine is a catecholamine made from tyrosine, and it acts only through metabotropic receptors: D1-type receptors generally raise cyclic AMP and favour plasticity and excitability, D2-type receptors lower it, and D2 receptors on dopamine terminals act as autoreceptors.

It signals surprise about reward. Recorded dopamine neurons fire a burst when a reward is better than predicted, stay at baseline when it is exactly as predicted, and pause when it is worse; with learning the burst moves from the reward to the cue that predicts it. This matches the prediction error of reinforcement-learning algorithms.

It decides which synapses learning keeps. Arriving shortly after a Hebbian coincidence, dopamine helps convert it into lasting change, which is how a reward can strengthen the connections that led to it (see Hebbian learning).

Losing it slows movement. Degeneration of the nigral neurons causes the motor signs of Parkinson's disease, treated with its precursor L-DOPA; many addictive drugs raise dopamine in the striatum directly, bypassing the prediction.

Dopamine teaches what works, glutamate stores what is.

Plasticity at glutamate synapses records associations; the dopamine signal says which of them paid off.

Questions: How does a dopamine neuron limit its own release? Dopamine terminals and cell bodies carry D2 receptors that respond to the dopamine they have just released. Through inhibitory G proteins these autoreceptors reduce calcium entry and release at the terminal, slow the cell's firing at the soma, and turn down the synthesis of new dopamine. The loop keeps release in range: blocking D2 autoreceptors, as some antipsychotics do in part, transiently increases dopamine release and synthesis. Together with reuptake by the dopamine transporter, this feedback shapes how long a burst of dopamine lasts. How could dopamine tell a synapse, seconds later, that it helped? Dopamine neurons fire more when an outcome is better than expected and less when it is worse, a reward prediction error broadcast to large parts of the brain. In three-factor learning rules, a synapse whose two neurons were active together sets a temporary chemical tag, an eligibility trace that fades over about a second or more, and the synapse changes only if dopamine or another modulator arrives while the tag is still there. The tag says which synapses were involved and the modulator says whether it went well, which assigns credit across the delay between an action and its result, with experimental support in the striatum, hippocampus and cortex. How can dopamine turn a Hebbian rule into learning from reward? A pure Hebbian rule strengthens every connection that takes part in firing a cell, whether the result was useful or not. In three-factor models, coincident activity of two cells only leaves a temporary mark on the synapse (an eligibility trace, lasting around a second), and the change becomes lasting only if a third signal arrives while the mark remains. Dopamine bursts after a better-than-expected outcome can play that role, and in the striatum, dopamine acting on D1 receptors shortly after a pre-post pairing has been shown to convert it into potentiation. The rule then strengthens the connections that preceded good outcomes, which is what reinforcement learning needs. What does a burst of dopamine signal? Recordings in monkeys showed that midbrain dopamine neurons burst when a reward arrives unexpectedly, stay at their baseline rate when a fully predicted reward arrives, and pause when a predicted reward fails to come. As the animal learns that a cue predicts the reward, the burst moves from the reward to the cue. This is the reward prediction error of reinforcement-learning theory, the difference between what happened and what was expected, as Schultz, Dayan and Montague pointed out in 1997. Broadcast to the striatum and frontal cortex, the signal tells recently active synapses whether the outcome was better or worse than predicted, so it acts as a teaching signal more than a pleasure signal. How is dopamine removed after release, and what do cocaine and amphetamine change? The dopamine transporter (DAT) on dopamine terminals pumps released dopamine back into the terminal, using the sodium gradient, where it is repackaged or broken down by monoamine oxidase; outside the cell catechol-O-methyltransferase degrades some of it, especially in the prefrontal cortex where DAT is scarce. Cocaine blocks DAT (and the noradrenaline and serotonin transporters), so each release lingers longer and spreads farther. Amphetamine enters the terminal through DAT, displaces dopamine from vesicles and makes the transporter run backwards, pushing dopamine out even without spikes. Both raise dopamine in the striatum far above what any natural reward produces, which is central to their addictive power.