Endocannabinoids mediate bidirectional striatal spike-timing dependent plasticity

Abstract : 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, it remained elusive whether synaptic plasticity occurs in response to limited event occurrences. To answer this question, we investigated if a low number of paired stimulations can induce plasticity in a major synaptic learning rule, the 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 decreasing the number of paired stimulations (below 50 pairings) whereas tLTP displays a biphasic profile: tLTP is observed for 75-100 pairings, absent for 25-50 pairings and reemerges for 5-10 pairings. This tLTP, induced by very few pairings (~5-10), depends on the endocannabinoid (eCB) system. This eCB-tLTP involves postsynaptic endocannabinoid synthesis, is homosynaptic and depends on type-1 cannabinoid receptor (CB1R) and transient receptor potential vanilloid type-1 (TRPV1) activation. eCB-tLTP occurs in both striatopallidal and striatonigral 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 paradigm. Thus, while usually considered as simply depressing synaptic function, endocannabinoids 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 behavioral flexibility.
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Journal of Physiology, Wiley, 2015, 593 (13), pp.2833-2849. 〈10.1113/JP270324〉
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Yihui Cui, Vincent Paille, Hao Xu, Stéphane Genet, Bruno Delord, et al.. Endocannabinoids mediate bidirectional striatal spike-timing dependent plasticity. Journal of Physiology, Wiley, 2015, 593 (13), pp.2833-2849. 〈10.1113/JP270324〉. 〈hal-01141205〉



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