Neuroscience Cluster Scientific Retreat
Chicago Cultural Center, Chicago, IL
September 17, 2009

Claire Piochon

Postdoctoral Fellow, Department of Neurobiology

Involvement of postsynaptic NMDA receptors in cerebellar LTD

N-methyl-D-aspartate receptors (NMDA-R), that are key players of neuronal function, are widely expressed by most of integrative neurons. Regarding this rule, adult cerebellar Purkinje cells have long been considered as an exception by lacking NMDA-R and were therefore used as peculiar model of plastic integrative neurons. This view has largely emerged from electrophysiological studies performed on rats or mice aged of two or three weeks, that, however, are not yet adult. Furthermore, immunohistochemistry or in situ hybridization studies indicated the presence of NR1 subunits in adult Purkinje cells, while NR2 subunits were detected only by some authors.

Recently, this controversial question of functional NMDA-Rs expression by Purkinje cells has been clarified. In mouse older than 2 months, adult Purkinje cells have been shown to express functional NMDA receptors. In patch-clamp whole-cell recordings, NMDA receptors participate in the excitatory postsynaptic current induced by the stimulation of the climbing fiber (CF-EPSC). This NMDA-mediated CF-EPSC is blocked by D-APV and external magnesium ions. Its I/V curve is typical of postsynaptic NMDA receptors and is blocked by intracellular MK801, showing that NMDA receptors are postsynaptic. Immunolabelings have also confirmed the presence of NR2-A/B subunits in Purkinje cells. The NMDA-mediated CF-EPSC, hardly detectable before 3 postnatal weeks, appears in all Purkinje cells by 21 postnatal days but is still very small at this age. Its amplitude increases subsequently until 12 weeks after birth. Thus, there is actually a "gap" in the developmental expression of NMDA-Rs in Purkinje cells, during the second and the third postnatal weeks.

In mature Purkinje cells, NMDA-Rs contribute to the depolarizing plateau of complex spikes and modulate the spikelets latency and number. The complex spike and its calcium signaling have been shown to play a crucial role in the induction of long term depression (LTD) at parallel fibers to Purkinje cell synapses. According to these observations and to the fact that NMDA receptors are highly permeable to calcium, our recent data indicate that these receptors would favor the induction of LTD at parallel fiber synapses: intracellular MK801, as well as D-APV bath application, inhibit the induction of LTD. We are presently studying the contribution of NMDA-receptors to spine calcium transients at CF input sites in the context of synaptic plasticity.

09/03/2009