Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity

Abstract

Single action potentials (APs) backpropagate into the higher-order dendrites of striatal spiny projection neurons during cortically driven “up” states. The timing of these backpropagating APs relative to the arriving corticostriatal excitatory inputs determines changes in dendritic calcium concentration. The question arises to whether this spike-timing relative to cortical excitatory inputs can also induce synaptic plasticity at corticostriatal synapses. Here we show that timing of single postsynaptic APs relative to the cortically evoked EPSP determines both the direction and the strength of synaptic plasticity in spiny projection neurons. Single APs occurring 30 ms before the cortically evoked EPSP induced long-term depression (LTD), whereas APs occurring 10 ms after the EPSP induced long-term potentiation (LTP). The amount of plasticity decreased as the time between the APs and EPSPs was increased, with the resulting spike-timing window being broader for LTD than for LTP. In addition, we show that dopamine receptor activation is required for this spike-timing-dependent plasticity (STDP). Blocking dopamine D 1 /D 5 receptors prevented both LTD and LTP induction. In contrast, blocking dopamine D 2 receptors delayed, but did not prevent, LTD and sped induction of LTP. We conclude (1) that, in combination with cortical inputs, single APs evoked in spiny projection neurons can induce both LTP and LTD of the corticostriatal pathway; (2) that the strength and direction of these synaptic changes depend deterministically on the AP timing relative to the arriving cortical inputs; (3) that, whereas dopamine D 2 receptor activation modulates the initial phase of striatal STDP, dopamine D 1 /D 5 receptor activation is critically required for striatal STDP. Thus, the timing of APs relative to cortical inputs alone is not enough to induce corticostriatal plasticity, implying that ongoing activity does not affect synaptic strength unless dopamine receptors are activated.