Striatal endocannabinoid-long-term potentiation mediates one-shot learning
The ability to learn and adapt its behavior from salient events encountered only once is crucial for survival. Few action potentials may be elicited during such one-shot learning, challenging usual learning frameworks. While the striatum is classically associated with incremental learning, some activity changes have been detected during the initial learning phase, but following several and/or long trials. Hence, the striatal engram for one-shot learning per se remains to be elucidated. Here, we show in a novel one-shot behavioral test in mice, the sticky tape avoidance test, that in vivo striatal long-term potentiation (LTP) emerges after a single, spontaneous and brief contact with an uncomfortable stimulus, and is associated with its subsequent avoidance that can last more than a month. We found that the non-classical endocannabinoid-mediated LTP, shown to occur in vitro after a small number of action potentials, is engaged during one-shot learning, even for brief exposures to the stimulus, and that paired cortico-striatal network activity shows behaviorally-correlated changes in activity consistent with endocannabinoid-mediated LTP induction during contact. Furthermore, we found impairments of one-shot learning in conditional knock-out mice affecting endocannabinoid-mediated LTP. Our results thus reveal new functional relevance of endocannabinoids in activity-dependent boundaries delineating synaptic plasticity expression in one-shot learning. This opens new avenues for understanding the effects of endo- and phyto-cannabinoids, including endocannabinoid-based medicinal drugs, on learning and memory.