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Zusammenfassung:
Single spikes are known to back-propagate into higher-order dendrites of striatal spiny projection neurons both during cortically driven Up-states and during Down-states. The timing of these back-propagating spikes relative to these arriving corticostriatal excitatory inputs determines dendritic calcium concentrations. Both, back-propagating spikes and changes in calcium concentration are required for synaptic plasticity to occur in the cortex. The question arises to whether single spikes can induce long-term synaptic plasticity at the corticostriatal synapse, and whether changes in spike-timing relative to cortical inputs determine the outcome of this plasticity.
Here we show that timing of postsynaptic single spikes relative to the arriving corticostriatal excitatory postsynaptic potential (EPSP) determines both direction and strength of synaptic plasticity in spiny projection neurons (n = 110 neurons). Single spikes occurring 30 ms before the cortically evoked EPSP induced strong long-term depression (LTD) (-28 ± 8%, 20-30 min post STDP protocol, n = 12) whereas spikes arriving 10 ms after the EPSP evoked long-term potentiation (LTP) (30 ± 11%, n = 11). These changes in synaptic efficacy decreased as the time between spikes and EPSPs was increased respectively. In addition, we show that STDP is under the strict control of dopamine receptors. Dopamine D1 receptor activation was necessary for both the increase and decrease of synaptic strength, as blocking dopamine D1 receptors prevented LTD induction (3 ± 9%, n = 7), as well as LTP induction (2 ± 4%, n = 9). In contrast, application of dopamine D2 antagonist delayed, but did not prevent LTD (-16 ± 10%, n = 6), and additionally did not change the induction of LTP (32 ± 12%, n = 8). We conclude: 1) in combination with cortical inputs, single spikes in striatal spiny projection neurons can induce both LTP and LTD of the corticostriatal pathway. 2) both the strength and direction of these changes depend deterministically on the spike-timing relative to the arriving cortical inputs. 3) striatal STDP depends on dopamine D1 receptor activation.