Input- and Cell-Type-Specific Endocannabinoid-Dependent LTD in the Striatum

Changes in basal ganglia plasticity at the corticostriatal and thalamostriatal levels are required for motor learning. Endocannabinoid-dependent long-term depression (eCB-LTD) is known to be a dominant form of synaptic plasticity expressed at these glutamatergic inputs; however, whether eCB-LTD can be induced at all inputs on all striatal neurons is still debatable. Using region-specific Cre mouse lines combined with optogenetic techniques, we directly investigated and distinguished between corticostriatal and thalamostriatal projections. We found that eCB-LTD was successfully induced at corticostriatal synapses, independent of postsynaptic striatal spiny projection neuron (SPN) subtype. Conversely, eCB-LTD was only nominally present at thalamostriatal synapses. This dichotomy was attributable to the minimal expression of cannabinoid type 1 (CB1) receptors on thalamostriatal terminals. Furthermore, coactivation of dopamine receptors on SPNs during LTD induction re-established SPN-subtype-dependent eCB-LTD. Altogether, our findings lay the groundwork for understanding corticostriatal and thalamostriatal synaptic plasticity and for striatal eCB-LTD in motor learning. [Display omitted] •eCB-LTD is induced specifically at corticostriatal, but not thalamostriatal, synapses•CB1 receptor expression levels are responsible for input specificity•eCB-LTD in the striatum is present independent of postsynaptic SPN subtype•Coactivation of dopamine receptors modulates eCB-LTD expression in the striatum Basal ganglia plasticity at glutamatergic synapses is required for motor learning. Wu et al. report that expression of endocannabinoid-dependent long-term depression (eCB-LTD) in the striatum is dependent on presynaptic input but independent of postsynaptic cell type. Furthermore, activation of dopamine receptors in the striatum bidirectionally modulates eCB-LTD expression.