title: Presynaptic NMDA receptors act as local high-gain glutamate detector in developing cerebellar molecular layer interneurons.
abstract: In the classical view, NMDA receptors (NMDARs) are located postsynaptically and play a pivotal role in excitatory transmission and synaptic plasticity. In developing cerebellar molecular layer interneurons (MLIs) however, NMDARs are known to be solely extra- or presynaptic and somewhat poorly expressed. Somatodendritic NMDARs are exclusively activated by glutamate spillover from adjacent synapses, but the mode of activation of axonal NMDARs remains unclear. Our data suggest that a volume transmission is likely to stimulate presynaptic NMDARs (preNMDARs) since NMDA puffs directed to the axon led to inward currents and Ca²⁺ transients restricted to axonal varicosities. Using local glutamate photoliberation, we show that pre- and post-synaptic NMDARs share the same voltage dependence indicating their containing NR2A/B subunits. Ca²⁺ transients elicited by NMDA puffs are eventually followed by delayed events reminding of the spontaneous Ca²⁺ transients (ScaTs) described at the basket cell/Purkinje cell terminals. Moreover, the presence of Ca²⁺ transients at varicosities located more than 5 μm away from the uncaging site indicates that the activation of preNMDARs sensitizes the Ca²⁺ stores in adjacent varicosities, a process that is abolished in the presence of a high concentration of ryanodine. Altogether, the data demonstrate that preNMDARs act as high-gain glutamate detectors.
authors.affiliation: Laboratoire de Physiologie Cérébrale, CNRS-UMR 8118, Université Paris Descartes, Université Paris Diderot, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Rossi
authors.forename: Thibault
authors.initials: T
authors.lastname: Collin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008027:Light; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology* / Q000528:radiation effects; D017661:Receptors, Presynaptic / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D012433:Ryanodine; D018698:Glutamic Acid