NMDA receptors act as molecular coincidence detectors because their activation requires both binding of the neurotransmitter glutamate and a level of postsynaptic depolarization sufficient to eliminate a voltage-dependent Mg²⁺ block. This coincidence detection could conceivably support the transformation of delay between two glutamatergic inputs into a burst duration code by amplifying the summated EPSPs in a voltage dependent manner. Directly coincident input EPSPs, caused by activation of AMPA receptors, would summate maximally and therefore reduce the Mg²⁺ block of NMDA receptors to a greater degree than EPSPs with non-overlapping onsets. Although a voltage-sensitive Mg²⁺ block on NMDA-R activation was not included in the models, a combination of model results (summated EPSPs produce membrane potentials between —50 and —40mV) and previous characterization of the range of voltage sensitivity of the Mg2+ block of NMDA-Rs in rat cerebellar granule cells (-70 to —60mV; D’Angelo, De Filippit, Rossi, and Taglietti, 1995) strongly suggests that this type of voltage-dependent input amplification is not responsible for generation of the burst duration code in ELL granular cells.

Sensitivity tests performed on models 1a and 2a revealed that temporal acuity of the granular cell response to EOCD and primary afferent inputs required the inclusion of electrical synapses for both inputs when glutamatergic synapses were modeled as NMDA-mediated excitatory postsynaptic currents (EPSCs). This is due to the slow t _rise and t _decay time constants of these currents, which last nearly 10-fold longer than AMPA-mediated EPSCs. Although addition of the voltage-dependent Mg²⁺ block to model NMDA-Rs could have acted to complement the amplifying effects of the I-NaP current, differences in initial depolarization would still need to depend on summation between two sufficiently sharp EPSPs or electrical inputs.

Another problematic aspect of NMDA-mediated EPSP amplification is the fact that the range of input depolarizations that must be discriminated in the granular cell is in a narrow window between —50 and —40mV. Voltage-dependent Mg²⁺ block of NMDA-R activation in granule cells has been shown to operate at a range much closer to resting potential, with little change in voltage-dependence above —60mV (D’Angelo, De Filippi, Rossi, and Taglietti, 1995). It would be possible to test this directly in an in vitro preparation of ELL granular cells by substituting other divalent cations for Mg²⁺ in the extracellular solution and stimulating juxtalobar and primary afferent inputs to the granular cell layer. If NMDA-mediated amplification were involved in generation of the burst duration code, granular cell responses would be expected to saturate at some maximum number of spikes over all input delays. Similarly, persistence of the transformation to a burst duration code in the presence of a chemical blockade against I-NaP and/or I-KM would suggest that the control of burst onset was due to this type of NMDA-mediated amplification.

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