Coincidence of cholinergic pauses, dopaminergic activation and depolarisation of spiny projection neurons drives synaptic plasticity in the striatum

Dopamine-dependent long-term plasticity is believed to be a cellular mechanism underlying reinforcement learning. In response to reward and reward-predicting cues, phasic dopamine activity potentiates the efficacy of corticostriatal synapses on spiny projection neurons (SPNs). Since phasic dopamine activity also encodes other behavioural variables, it is unclear how postsynaptic neurons identify which dopamine event is to induce long-term plasticity. Additionally, it is unknown how phasic dopamine released from arborised axons can potentiate targeted striatal synapses through volume transmission. To examine these questions we manipulated striatal cholinergic interneurons (ChIs) and dopamine neurons independently in two distinct in vivo paradigms. We report that long-term potentiation (LTP) at corticostriatal synapses with SPNs is dependent on the coincidence of pauses in ChIs and phasic dopamine activation, critically accompanied by SPN depolarisation. Thus, the ChI pause defines the time window for phasic dopamine to induce plasticity, while depolarisation of SPNs constrains the synapses eligible for plasticity. It remains unclear how corticostriatal synapses utilize reward prediction error signaling in order to reinforce reward-related behaviors. Here, the authors show that potentiation of corticostriatal synapses requires phasic dopamine activation, pauses in striatal cholinergic interneuron firing, and depolarization of spiny projection neurons.

Automated summary

Dopamine-dependent long-term plasticity is a cellular mechanism underlying reinforcement learning. The coincidence of phasic dopamine activation and pauses in striatal cholinergic interneuron firing plays a critical role in long-term potentiation of corticostriatal synapses.