Pre and post synaptic NMDA effects targeting Purkinje cells in the mouse cerebellar cortex.

Etienne Lonchamp,Antoine Valera,Frédéric Gambino,Frédéric Doussau,Jean-Louis Bossu,Bernard Poulain,Jean Luc Dupont

doi:10.1371/journal.pone.0030180

Etienne Lonchamp, Antoine Valera + Show 5 more

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https://doi.org/10.1371/journal.pone.0030180

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Abstract

N-methyl-D-aspartate (NMDA) receptors are associated with many forms of synaptic plasticity. Their expression level and subunit composition undergo developmental changes in several brain regions. In the mouse cerebellum, beside a developmental switch between NR2B and NR2A/C subunits in granule cells, functional postsynaptic NMDA receptors are seen in Purkinje cells of neonate and adult but not juvenile rat and mice. A presynaptic effect of NMDA on GABA release by cerebellar interneurons was identified recently. Nevertheless whereas NMDA receptor subunits are detected on parallel fiber terminals, a presynaptic effect of NMDA on spontaneous release of glutamate has not been demonstrated. Using mouse cerebellar cultures and patch-clamp recordings we show that NMDA facilitates glutamate release onto Purkinje cells in young cultures via a presynaptic mechanism, whereas NMDA activates extrasynaptic receptors in Purkinje cells recorded in old cultures. The presynaptic effect of NMDA on glutamate release is also observed in Purkinje cells recorded in acute slices prepared from juvenile but not from adult mice and requires a specific protocol of NMDA application.

Highlights

NMDA receptors are glutamate activated ion channels that shape the response of postsynaptic neurons and regulate presynaptic neurotransmitter release ([1,2] for reviews)
The response to NMDA was characterized firstly in Purkinje cells recorded from organotypic slice cultures at a holding potential of 240 mV, and secondly in Purkinje cells recorded from acute slices at a holding of 260 mV
Data were expressed as a function of age of Purkinje cells or the culture, whereas in acute slices the data were reported as a function of the postnatal age of the animal

Summary

Introduction

NMDA receptors are glutamate activated ion channels that shape the response of postsynaptic neurons and regulate presynaptic neurotransmitter release ([1,2] for reviews). The presynaptic effect is mediated either directly by NMDA receptors localized on axons or synaptic boutons, or indirectly by postsynaptic receptors allowing the release of retrograde messengers acting on the presynaptic element ([2,4] for reviews). Functional NMDA receptor channels are tetrameric assemblies formed by the association between two NR1 subunits (represented by a family of eight different splice variants) with NR2A-D subunits. NMDA receptor subunit expression is regulated and the NR2A/NR2B ratio changes with development, sensory experience and synaptic plasticity ([5] for a review)

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