P239 Striatal endocannabinoid long-term potentiation mediates one-shot learning
Charlotte PIETTE1, Arnaud HUBERT2,3, Sylvie PEREZ1, Hugues BERRY2,3, Jonathan TOUBOUL4#, Laurent VENANCE1#
1Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Université PSL, 75005 Paris, France
2INRIA, Villeurbanne, France
3University of Lyon, LIRIS UMR5205, Villeurbanne, France4Brandeis University, MA Waltham, USA
#: co-senior authors
Correspondence:laurent.venance@college-de-france.fr,jtouboul@brandeis.edu
Introduction
One-shot learning - the behavioral and neuronal mechanisms underlying the acquisition of a long-term memory after a unique and brief experience -, is a crucial mechanism for developing adaptive responses. Yet its neural correlates remain elusive(see for review: Piette et al., 2020). Here, we aimed at elucidating how changes in cortico-striatal dynamics contribute to one-shot learning. Considering that a brief exposure to a stimulus involves only a few spikes and based on our earlier work uncovering a new form of endocannabinoid-dependent synaptic potentiation (eCB-LTP) induced by a very low number of temporally coupled cortical and striatal spikes (Cui et al., 2015 & 2016; Xu et al. 2018), we hypothesize that the endocannabinoid system could underlie striatal one-shot learning.
Methods
We first developed a one-shot learning test in which mice learn to avoid contact with an adhesive tape after a single exposure. We then usedin vivoandex vivoelectrophysiological recordings in the striatum of behaving mice to probe cortico-striatal plasticity and the specific contribution of the endocannabinoid system. In addition, based on Neuropixels recordings of cortical and striatal neuronsin vivo, we developed a mathematical model to test the induction of eCB-LTP. Finally, we test the performance of transgenic mouse strains in which eCB-LTP is altered and in mice in which local striatal infusion of drugs prevent either NMDA or eCB-mediated plasticities.
Results
The “sticky tape avoidance test” proved an efficient one-shot learning test, since following a single and short (< 20 seconds) uncomfortable contact with an adhesive tape, mice avoided further contact. We found a cortico-striatal long-term synaptic potentiation emerged 24h after short contacts with the tape. Furthermore, thedetailed computational model of cortico-striatal synapse predicted an increased occurrence of eCB-LTP induction events during contact.Indeed,ex vivowhole-cell patch-clamp recordings revealed an occlusion of eCB-LTP in mice shortly exposed to the sticky tape. In addition, we showed that eCB-LTP knock-out mice and AM251-infused mice exhibited impaired one-shot learning, while no significant difference was observed between D-AP5 and saline-infused mice.
Discussion
These multiple approaches demonstrate that eCBs underlie one-shot learning.Overall,these findings revisit the recently challenged view that dorsolateral striatum is involved mostly in habit formation. For the first time, they outline the temporal and activity-dependent boundaries delineating the expression of a synaptic plasticity pathway within a learning paradigm. Such insights into the nature and roles of eCB-based plasticity will also offer keys to interpreting the wide array of functions of the eCB system.
Acknowledgements
We thank S. R. Datta and the Venance lab members for helpful suggestions and critical comments on the manuscript. Camille Chataing and Emma Idzikowkski for their help on the behavioral experiments at one-month retrieval interval. Yves Dupraz (CIRB micromechanics workshop) for the building of the arenas, cross-maze and electrophysiology micromechanics.
References
1. Piette, C., Touboul, J., Venance, L. (2020). Engrams of fast learning.Front. Cell. Neurosci.,14. 10.3389/fncel.2020.575915
2.Cui Y., et al.(2015).Endocannabinoids mediate bidirectional striatal spike-timing-dependent plasticity.J. Physiol.593, 2833–2849. 10.1113/JP270324
3. Cui Y., et al.(2016).Endocannabinoid dynamics gate spike-timing dependent depression and potentiation.eLife5:e13185. 10.7554/eLife.13185
4. Xu H., et al.(2018).Dopamine-endocannabinoid interactions mediate spike-timing-dependent potentiation in the striatum.Nat. Commun.9:4118. 10.1038/s41467-018-06409-5
