Abstract
Long-term synaptic plasticity is believed to be the cellular substrate of learning and memory. Synaptic plasticity rules are defined by the specific complement of receptors at the synapse and the associated downstream signaling mechanisms. In young rodents, at the cerebellar synapse between granule cells (GC) and Purkinje cells (PC), bidirectional plasticity is shaped by the balance between transcellular nitric oxide (NO) driven by presynaptic N-methyl-D-aspartate receptor (NMDAR) activation and postsynaptic calcium dynamics. However, the role and the location of NMDAR activation in these pathways is still debated in mature animals. Here, we show in adult rodents that NMDARs are present and functional in presynaptic terminals where their activation triggers NO signaling. In addition, we find that selective genetic deletion of presynaptic, but not postsynaptic, NMDARs prevents synaptic plasticity at parallel fiber-PC (PF-PC) synapses. Consistent with this finding, the selective deletion of GC NMDARs affects adaptation of the vestibulo-ocular reflex. Thus, NMDARs presynaptic to PCs are required for bidirectional synaptic plasticity and cerebellar motor learning.
| Original language | English |
|---|---|
| Article number | e2102635118 |
| Number of pages | 9 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 118 |
| Issue number | 37 |
| DOIs | |
| Publication status | Published - 14 Sept 2021 |
Bibliographical note
ACKNOWLEDGMENTS. This work was supported by the program “Investissements d’Avenir” from the French Government, implemented by Agence Nationale de la Recherche, references: ANR-10-LABX-54 MEMOLIFE, ANR-11-IDEX0001-02 PSL* Research University. M.S. was funded by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) Aard- en Levenswetenschappen (ALW-Veni) and European Research Council Starting Grant (ERC-Stg).C.I.D.Z. was supported by FP7-C7 European Commission, ZonMw, NWOExacte en Natuurwetenschappen (ENW-Klein), European Research Council
(Advanced Grant and Proof of Concept Grant), Medical NeuroDelta Programme, Topsector Life Sciences & Health (Innovative Neurotechnology for
Society), and the Albinism Vriendenfonds Netherlands Institute for Neuroscience. G.B. was funded by Région Ile de France, Fondation pour la Recherche
Medicale (FRM), and Labex MEMOLIFE. A.E.G. was supported by the National
Science Foundation (NSF) Graduate Research Fellowship Program (GRFP) and
the University of California, San Francisco Discovery Fellows Program. The
funders had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript. We thank R. de Avila Freire and
L. Post for technical assistance, and B. Barbour, R.S. Larsen, P.L. Reeson, E. Jones,
M. Mukundan, and C. Wang for comments on the manuscript.