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Application Domains
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Section: New Results

Dopamine interacts with endocannabinoids to regulate spike timing dependent plasticity

participants: H. Berry, I. Prokin

Dopamine modulates striatal synaptic plasticity, a key substrate for action selection and procedural learning. Thus, characterizing the repertoire of activity-dependent plasticity in striatum and its dependence on dopamine is of crucial importance. In collaboration with L. Venance Lab (CIRB, Collège de France) we recently unraveled a striatal spike-timing-dependent long-term potentiation (tLTP) mediated by endocannabinoids (eCBs) and induced with few spikes ( 5-15). Whether this eCB-tLTP interacts with the dopaminergic system remains to be investigated. We found that eCB-tLTP is impaired in a rodent model of Parkinson's disease and rescued by L-DOPA. Dopamine controls eCB-tLTP via dopamine type-2 receptors (D2R) located presynaptically in cortical terminals. Dopamine-endocannabinoid interactions via D2R are required for the emergence of tLTP in response to few coincident pre-and post-synaptic spikes and control eCB-plasticity by modulating the long-term potentiation (LTP)/depression (LTD) thresholds. While usually considered as a depressing synaptic function, our results show that eCBs in the presence of dopamine constitute a versatile system underlying bidirectional plasticity implicated in basal ganglia pathophysiology. These results have been published in Nature Communications [23]