Impact of NMDA Receptor Overexpression on Cerebellar Purkinje Cell Activity and Motor Learning.

ABSTRACT

In many brain regions involved in learning NMDA receptors (NMDARs) act as coincidence detectors of pre- and postsynaptic activity, mediating Hebbian plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in the cerebellar cortex, which is critical for procedural learning, shows virtually no postsynaptic NMDARs. Why is this? Here, we address this question by generating and testing independent transgenic lines that overexpress NMDAR containing the type 2B subunit (NR2B) specifically in PCs. PCs of the mice that show larger NMDA-mediated currents than controls at their PF input suffer from a blockage of long-term potentiation (LTP) at their PF-PC synapses, while long-term depression (LTD) and baseline transmission are unaffected. Moreover, introducing NMDA-mediated currents affects cerebellar learning in that phase-reversal of the vestibulo-ocular reflex (VOR) is impaired. Our results suggest that under physiological circumstances PC spines lack NMDARs postsynaptically at their PF input so as to allow LTP to contribute to motor learning.