Concurrent Thalamostriatal and Corticostriatal Spike-Timing-Dependent Plasticity and Heterosynaptic Interactions Shape Striatal Plasticity Map

The striatum integrates inputs from the cortex and thalamus, which display concomitant or sequential activity. The striatum assists in forming memory, with acquisition of the behavioral repertoire being associated with corticostriatal (CS) plasticity. The literature has mainly focused on that CS plasticity, and little remains known about thalamostriatal (TS) plasticity rules or CS and TS plasticity interactions. We undertook here the study of these plasticity rules. We found bidirectional Hebbian and anti-Hebbian spike-timing-dependent plasticity (STDP) at the thalamic and cortical inputs, respectively, which were driving concurrent changes at the striatal synapses. Moreover, TS- and CS-STDP induced heterosynaptic plasticity. We developed a calcium-based mathematical model of the coupled TS and CS plasticity, and simulations predict complex changes in the CS and TS plasticity maps depending on the precise cortex–thalamus–striatum engram. These predictions were experimentally validated using triplet-based STDP stimulations, which revealed the significant remodeling of the CS-STDP map upon TS activity, which is notably the induction of the LTD areas in the CS-STDP for specific timing regimes. TS-STDP exerts a greater influence on CS plasticity than CS-STDP on TS plasticity. These findings highlight the major impact of precise timing in cortical and thalamic activity for the memory engram of striatal synapses.