Presynaptic N-methyl-d-aspartate receptors at the parallel fiber–Purkinje cell synapse

Presynaptic N-methyl-d-aspartate receptors at the parallel fiber–Purkinje cell synapse

Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8544, Ecole Normale Supérieure, 46, rue d'Ulm, 75005 Paris, France

Communicated by Clay M. Armstrong, University of Pennsylvania School of Medicine, Philadelphia, PA (received for review December 20, 1999)

Abstract

At the cerebellar synapse between the parallel fibers (PFs) and the Purkinje cells in the cerebellum, we have found that application of N-methyl-d-aspartate (NMDA) reversibly depresses the postsynaptic current. We present evidence that this depression involves NMDA receptors located on the presynaptic axons and requires that the NMDA application be combined with action potentials in the PFs. Unexpectedly, unlike other modulations mediated by presynaptic receptors, the NMDA-induced inhibition does not involve a depression of transmitter release. Because it is blocked by both nitric oxide synthase and soluble guanylate cyclase inhibitors, we propose that it involves a trans-synaptic mechanism in which NO released by the PFs decreases the glutamate sensitivity of the Purkinje cell.

Footnotes

↵ * To whom reprint requests should be addressed at: Laboratoire de Neurobiologie, Ecole Normale Supérieure, 46, rue d'Ulm, 75005, Paris, France. E-mail: casado{at}wotan.ens.fr.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.200354297.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.200354297
Abbreviations:

NMDA,

N-methyl-d-aspartate;

PF,

parallel fiber;

PC,

Purkinje cell;

EPSC,

excitatory postsynaptic current;

BAPTA,

1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate;

APV,

2-amino-5-phosphonovaleric acid;

l-NAME,

N(G)nitro-l-arginine methyl ester;

ODQ,

1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one;

DPCPX,

8-cyclopentyl-1,3-dipropylxanthine;

PPF,

paired pulse facilitation;

NOS,

NO synthase