[en] Burst firing in substantia nigra pars compacta dopamine neurons is a critical biomarker temporally associated to movement initiation. This phasic change is generated by the tonic activation of NMDARs but the respective role of synaptic versus extrasynaptic NMDARs in the ignition of a burst and what is their level of activation remains unknown. Using ex vivo electrophysiological recordings from adolescent rats, we demonstrate that extrasynaptic NMDARs are the primary driver of burst firing. This pool of receptors is recruited during intense synaptic activity via spillover of glutamate and require the binding of NMDAR co-agonist glycine for full activation. Basal synaptic transmission activating only synaptic NMDARs with the support of D-serine is insufficient to generate a burst. Notably, both synaptic and extrasynaptic NMDARs share the same subunit composition but are regulated by distinct co-agonists. Location of NMDARs and regionalization of co-agonists but not NMDAR subunit composition underly burst generation and may serve as a guideline in understanding the physiological role of dopamine in signaling movement.
Motta, Zoraide; The Protein Factory 2.0 Lab, Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, via Dunant, Varese 3-21100, Italy
Vandries, Laura ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Seutin, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Jehasse, Kevin ; Université de Liège - ULiège > Montefiore Institute of Electrical Engineering and Computer Science
Caldinelli, Laura; The Protein Factory 2.0 Lab, Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, via Dunant, Varese 3-21100, Italy
Pollegioni, Loredano; The Protein Factory 2.0 Lab, Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, via Dunant, Varese 3-21100, Italy
Engel, Dominique ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Language :
English
Title :
Glycine-gated extrasynaptic NMDARs activated during glutamate spillover drive burst firing in nigral dopamine neurons.
We thank Dr. Jean-Marc Goaillard for helpful comments on the manuscript, Sandy El Sayed and Laurent Massotte for technical assistance and the GIGA-imaging platform for using the confocal microscope and Imaris. We also thank particularly Alexandre Hego for his excellent help with analysis using Imaris and Aurore Beuchet for analyzing data. This work was supported by the Belgian FNRS (FRIA), the Fondation Leon Fredericq, Prix de l\u2019espoir from Marie-Jos\u00E9 De Ridder (to S. R.) and Fonds facultaires de l\u2019ULi\u00E8ge (to D.E). Z.M. is a PhD student of the Life Sciences and Biotechnology course at the University of Insubria. L.P. thanks the support from FAR Fondo di Ateneo per la Ricerca. D.E. thanks Dr. Laurent Nguyen for his support and for integrating D.E. in his (L.N.) Group and Dr. Sophie Laguesse for sharing data.We thank Dr. Jean-Marc Goaillard for helpful comments on the manuscript, Sandy El Sayed and Laurent Massotte for technical assistance and the GIGA-imaging platform for using the confocal microscope and Imaris. We also thank particularly Alexandre Hego for his excellent help with analysis using Imaris and Aurore Beuchet for analyzing data. This work was supported by the Belgian FNRS (FRIA), the Fondation Leon Fredericq, Prix de l'espoir from Marie-Jos\u00E9 De Ridder (to S. R.) and Fonds facultaires de l'ULi\u00E8ge (to D.E). Z.M. is a PhD student of the Life Sciences and Biotechnology course at the University of Insubria. L.P. thanks the support from FAR Fondo di Ateneo per la Ricerca. D.E. thanks Dr. Laurent Nguyen for his support and for integrating D.E. in his (L.N.) Group and Dr. Sophie Laguesse for sharing data.
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