Striatal endocannabinoids drive one-shot learning.

Authors

Charlotte Piette, Arnaud Hubert, Sylvie Perez, Jérémy Peixoto, Nicolas Gervasi, Hugues Berry, Jonathan Touboul, Laurent Venance

Published in

Nature neuroscience. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

One-shot learning-the ability to form memories after a single, brief salient event-is essential for behavioral flexibility in a dynamic world. However, how one-shot learning unfolds in the brain and whether it relies on distinct plasticity mechanisms remains unknown. Here we show that a nonclassical plasticity mechanism requiring only a few stimulations-endocannabinoid-mediated long-term potentiation (eCB-LTP)-underlies one-shot learning in the striatum. To do so, we developed a one-shot behavioral paradigm-the sticky tape avoidance test-in which mice learn to avoid a piece of sticky tape after a spontaneous single and brief contact. Brief, but not prolonged, contacts drive striatal potentiation in vivo and engage coordinated cortical-striatal activity patterns consistent with eCB-LTP induction, as corroborated by ex vivo electrophysiology and computational modeling. Finally, genetic and pharmacological disruptions of eCB-LTP impaired one-shot learning. These results highlight the essential role of nonclassical plasticity mechanisms in supporting memory formation after a single experience.

PMID:
42567967
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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