Dopamine-endocannabinoid interactions mediate spike-timing-dependent potentiation in the striatum

Nat Commun. 2018 Oct 8;9(1):4118. doi: 10.1038/s41467-018-06409-5.

Abstract

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. 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. Here, we report 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Antiparkinson Agents / pharmacology
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Endocannabinoids / metabolism*
  • Levodopa / pharmacology
  • Long-Term Potentiation / physiology*
  • Long-Term Synaptic Depression / physiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neostriatum / cytology
  • Neostriatum / metabolism
  • Neostriatum / physiology*
  • Parkinson Disease / physiopathology
  • Parkinson Disease / prevention & control
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / metabolism

Substances

  • Antiparkinson Agents
  • Endocannabinoids
  • Receptors, Dopamine D2
  • Levodopa
  • Dopamine