title: Endocannabinoids mediate bidirectional striatal spike-timing-dependent plasticity.
abstract: CONCLUSIONS
  Although learning can arise from few or even a single trial, synaptic plasticity is commonly assessed under prolonged activation. Here, we explored the existence of rapid responsiveness of synaptic plasticity at corticostriatal synapses in a major synaptic learning rule, spike-timing-dependent plasticity (STDP). We found that spike-timing-dependent depression (tLTD) progressively disappears when the number of paired stimulations (below 50 pairings) is decreased whereas spike-timing-dependent potentiation (tLTP) displays a biphasic profile: tLTP is observed for 75-100 pairings, is absent for 25-50 pairings and re-emerges for 5-10 pairings. This tLTP induced by low numbers of pairings (5-10) depends on activation of the endocannabinoid system, type-1 cannabinoid receptor and the transient receptor potential vanilloid type-1. Endocannabinoid-tLTP may represent a physiological mechanism operating during the rapid learning of new associative memories and behavioural rules characterizing the flexible behaviour of mammals or during the initial stages of habit learning.
  Synaptic plasticity, a main substrate for learning and memory, is commonly assessed with prolonged stimulations. Since learning can arise from few or even a single trial, synaptic strength is expected to adapt rapidly. However, whether synaptic plasticity occurs in response to limited event occurrences remains elusive. To answer this question, we investigated whether a low number of paired stimulations can induce plasticity in a major synaptic learning rule, spike-timing-dependent plasticity (STDP). It is known that 100 pairings induce bidirectional STDP, i.e. spike-timing-dependent potentiation (tLTP) and depression (tLTD) at most central synapses. In rodent striatum, we found that tLTD progressively disappears when the number of paired stimulations is decreased (below 50 pairings) whereas tLTP displays a biphasic profile: tLTP is observed for 75-100 pairings, absent for 25-50 pairings and re-emerges for 5-10 pairings. This tLTP, induced by very few pairings (∼5-10) depends on the endocannabinoid (eCB) system. This eCB-dependent tLTP (eCB-tLTP) involves postsynaptic endocannabinoid synthesis, requires paired activity (post- and presynaptic) and the activation of type-1 cannabinoid receptor (CB1R) and transient receptor potential vanilloid type-1 (TRPV1). eCB-tLTP occurs in both striatopallidal and striatonigral medium-sized spiny neurons (MSNs) and is dopamine dependent. Lastly, we show that eCB-LTP and eCB-LTD can be induced sequentially in the same neuron, depending on the cellular conditioning protocol. Thus, while endocannabinoids are usually thought simply to depress synaptic function, they also constitute a versatile system underlying bidirectional plasticity. Our results reveal a novel form of synaptic plasticity, eCB-tLTP, which may underlie rapid learning capabilities characterizing behavioural flexibility.
authors: Centre for Interdisciplinary Research in Biology, College de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris, France.|University Pierre et Marie Curie, ED 158, Paris, France.
authors: Yihui
authors: Y
authors: Cui
authors: Centre for Interdisciplinary Research in Biology, College de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris, France.|University Pierre et Marie Curie, ED 158, Paris, France.
authors: Vincent
authors: V
authors: Paillé
authors: Centre for Interdisciplinary Research in Biology, College de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris, France.|University Pierre et Marie Curie, ED 158, Paris, France.
authors: Hao
authors: H
authors: Xu
authors: University Pierre et Marie Curie, ED 158, Paris, France.|Institute of Intelligent Systems and Robotics (ISIR), Paris, France.
authors: Stéphane
authors: S
authors: Genet
authors: University Pierre et Marie Curie, ED 158, Paris, France.|Institute of Intelligent Systems and Robotics (ISIR), Paris, France.
authors: Bruno
authors: B
authors: Delord
authors: Centre for Interdisciplinary Research in Biology, College de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris, France.|University Pierre et Marie Curie, ED 158, Paris, France.
authors: Elodie
authors: E
authors: Fino
authors: INRIA, Villeurbanne, France.|University of Lyon, LIRIS UMR5205, Villeurbanne, France.
authors: Hugues
authors: H
authors: Berry
authors: Centre for Interdisciplinary Research in Biology, College de France, INSERM U1050, CNRS UMR7241, Labex Memolife, Paris, France.|University Pierre et Marie Curie, ED 158, Paris, France.
authors: Laurent
authors: L
authors: Venance
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D063388:Endocannabinoids / Q000494:pharmacology*; D005260:Female; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels