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The Journal of Neuroscience, October 3, 2007, 27(40):10797-10809; doi:10.1523/JNEUROSCI.2422-07.2007

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Cellular/Molecular
NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell

Claire Piochon,¹ Theano Irinopoulou,² Daniel Brusciano,¹ Yannick Bailly,³ Jean Mariani,^1,4 and Carole Levenes¹

¹Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 7102, Centre National de la Recherche Scientifique (CNRS), Laboratoire Neurobiologie des Processus Adaptifs, Équipe Développement et Vieillissement du Système Nerveux, 75005 Paris, France, ²Unité 536/Unité 706, Inserm, Institut du Fer à Moulin, F-75005 Paris, France, ³Neurotransmission et Sécrétion Neuroendocrine, Institut des Neurosciences Cellulaires et Intégratives UMR 7168, CNRS, Université Louis Pasteur, 67084 Strasbourg, France, and ⁴Hôpital Charles Foix, Assistance Publique–Hôpitaux de Paris, 94 Ivry sur Seine, France

Correspondence should be addressed to Dr. Carole Levenes, Université Pierre et Marie Curie, Équipe Développement et Vieillissement du Système Nerveux, Case Courrier 14, 9 quai St. Bernard, 75005 Paris, France. Email: carole.levenes{at}snv.jussieu.fr

Among integrative neurons displaying long-term synaptic plasticity, adult Purkinje cells seemed to be an exception by lacking functional NMDA receptors (NMDA-Rs). Although numerous anatomical studies have shown both NR1 and NR2 NMDA-R subunits in adult Purkinje cells, patch-clamp studies failed to detect any NMDA currents. Using more recent pharmacological and immunodetection tools, we demonstrate here that Purkinje cells from adult mice respond to exogenous NMDA application and that postsynaptic NMDA-Rs carry part of the climbing fiber-mediated EPSC (CF-EPSC), with undetectable contribution from presynaptic or polysynaptic NMDA currents. We also detect NR2-A/B subunits in adult Purkinje cells by immunohistochemistry. The NMDA-mediated CF-EPSC is barely detectable before 3 weeks postnatal. From the end of the third week, the number of cells displaying the NMDA-mediated CF-EPSC rapidly increases. Soon, this EPSC becomes detectable in all the Purkinje cells but is still very small. Its amplitude continues to increase until 12 weeks after birth. In mature Purkinje cells, we show that the NMDA-Rs contribute to the depolarizing plateau of complex spikes and increase their number of spikelets. Together, these observations demonstrate that mature Purkinje cells express functional NMDA receptors that become detectable in CF-EPSCs at 21 d after birth and control the complex spike waveform.

Key words: Purkinje cell; cerebellum; development; climbing fiber; complex spike; NMDA

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Received July 4, 2006; revised Aug. 9, 2007; accepted Aug. 21, 2007.

Correspondence should be addressed to Dr. Carole Levenes, Université Pierre et Marie Curie, Équipe Développement et Vieillissement du Système Nerveux, Case Courrier 14, 9 quai St. Bernard, 75005 Paris, France. Email: carole.levenes{at}snv.jussieu.fr

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