The Journal of Neurophysiology Vol. 87 No. 4 April 2002, pp. 1948-1959
Copyright ©2002 by the American Physiological Society

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

Department of Physiology and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611

Billups, Daniela, Ying-Bing Liu, Susanne Birnstiel, and N. Traverse Slater. NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells. J. Neurophysiol. 87: 1948-1959, 2002. The properties of N-methyl-D-aspartate (NMDA) receptor-mediated currents at the giant cerebellar mossy-fiber unipolar brush cell (UBC) synapse were compared with those of adjacent granule cells using patch-clamp recording methods in thin slices of rat cerebellar nodulus. In UBCs, NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) decayed as a single exponential whose time constant was independent of membrane potential. The EPSC was reduced in all cells by the NR1/NR2B-selective antagonist ifenprodil, and the Zn²⁺ chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) produced a transient potentiation in 50% of cells. In contrast, the NMDA EPSC in granule cells decayed as a double exponential that dramatically switched to a slower rate at positive membrane potentials. The synaptic response in some granule cells also displayed a late second peak at positive potentials, and in others, activation of mossy fibers produced repetitive trains of EPSCs indicating they may be postsynaptic to the UBC network. Single-channel recordings of outside-out somatic patches from UBCs in magnesium-free solution revealed only high-conductance (50 pS) channels whose open time was increased with depolarization, but the opening frequency was decreased to yield a low (p_o = 0.0298), voltage-independent opening probability. Lowering extracellular calcium (2.5-0.25 mM) had no effects on channel gating, although an increase of single-channel conductance was observed at lower calcium concentrations. Taken together, the data support the notion that the NMDA receptor in UBCs may comprise both NR1/NR2A and NR1/NR2B receptors. Furthermore, the properties of the EPSC in these two classes of feedforward glutamatergic interneurons display fundamental differences that may relate to their roles in synaptic integration.