The ability of individual neurons to modulate the gain of their input-output function is important for information processing in the brain. In a recent study (Mitchell & Silver, 2003), shunting inhibition was found to modulate the gain of cerebellar granule cells subjected to simulated currents through AMPA receptor synapses. Here we investigate the effect on gain modulation resulting from adding the currents mediated by NMDA receptors to a compartmental model of the granule cell. With only AMPA receptors, the changes in gain induced by shunting inhibition decreased gradually with the average firing rate of the afferent mossy fibers. With NMDA receptors present, this decrease was more rapid, therefore narrowing the bandwidth of mossy fiber firing rates available for gain modulation. The deterioration of gain modulation was accompanied by a reduced variability of the input current and saturation of NMDA receptors. However, when the output of the granule cell was plotted as a function of the average input current instead of the input firing frequency, both models showed very similar response curves and comparable gain modulation. We conclude that NMDA receptors do not directly impair gain control by shunting inhibition, but the effective bandwidth decreases as a consequence of the increased total charge transfer.

We have examined a model by Holmes and Levy (1990) of the induction of associative long-term potentiation (LTP) by a rise in the free Ca 2+ concentration ([Ca 2+ ]) after synaptic activation of dendritic spines. The previously reported amplification of the change in [Ca 2+ ] caused by coactivation of several synapses was found to be quite sensitive to changes in the permeability of the N -methyl-D-aspartate (NMDA) receptor channels to Ca 2+ . Varying this parameter indicated that maximum amplification is obtained at values that are close to Ca 2+ permeabilities reported in the literature. However, amplification failed if permeability is reduced by more than 50%. We also found that the maximum free [Ca 2+ ] reached in an individual spine during synaptic coactivation of several spines depended on the location of that spine on the dendritic tree. Distal spines attained a higher [Ca 2+ ] than proximal ones, with differences of up to 80%. The implications of this result for the uniformity of induction of associative LTP in spines in different regions of the dendrite are discussed.