Postsynaptic currents in deep cerebellar nuclei

Postsynaptic currents were studied by whole cell recordings in visually identified large neurons of the deep cerebellar nuclei (DCN) in slices of 4- to 11-day-old mice, Spontaneous postsynaptic currents were abolished by the GABAA receptor antagonist bicuculline and had a single-exponential decay with a mean time constant of 13.6 \ub1 3.2 (SD) ms. Excitatory postsynaptic currents (EPSCs) were evoked in 48/56 neurons recorded. The addition of AMPA and N-methyl-D-aspartate (NMDA) receptor antagonists together completely abolished all synaptic responses. In 1 mM [Mg2+]o and at a holding potential of -60 mV, the peak amplitude of the NMDA component of the EPSC (NMDA-EPSC) was 83.2 \ub1 21.2% of the AMPA component (AMPA-EPSC). This indicates that in DCN neurons, at a physiological [Mg2+]o and at the resting membrane potential, NMDA receptors contribute to the synaptic signal. AMPA-EPSCs had a linear current-voltage relationship with a reversal potential of +2.3 \ub1 0.4 mV and a single-exponential decay with a voltage-dependent time constant that at -60 mV was 7.1 \ub1 3.3 ms. In 10 \u3bcM glycine and 1 mM [Mg2+]o, the I-V relationship of NMDA-EPSCs had a reversal potential of -0.5 \ub1 3.3 mV and a maximal inward current at -33.4 \ub1 5.8 mV. The apparent dissociation constant (KD) of Mg2+ for the NMDA receptor-channel at -60 mV, measured by varying [Mg2+]o, was 135.5 \ub1 55.3 \u3bcM, and when measured by fitting the I-V curves with a theoretical function, it was 169.9 \ub1 119.5 \u3bcM. Thus in the DCN, NMDA receptors have a sensitivity to Mg2+ that corresponds to subunits that are weakly blocked by this ion (\u3b53 and \u3b54) of which the DCN express \u3b54. NMDA-EPSCs had a double-exponential decay with voltage-dependent time constants that at -60 mV were 20.2 \ub1 8.9 and 136.4 \ub1 62.8 ms. At positive voltages, the time constants were slower and their contributions were about equal, while in the negative slope conductance region of the I-V curve, the faster time constant became predominant, conferring faster kinetics to the EPSC. The weak sensitivity to Mg2+ of NMDA receptors, together with a relatively fast kinetics, provide DCN neurons with strong excitatory inputs in which fast dynamic signals are relatively well preserved