Computer simulations of NMDA and non-NMDA receptor-mediated synaptic drive: sensory and supraspinal modulation of neurons and small networks.

1. The segmental locomotor network in lamprey can generate the rhythmic burst pattern underlying locomotion when it is driven via synaptic glutamate receptors. Lower rates of activity can be evoked by activation of N-methyl-D-aspartate (NMDA) receptors, whereas a rapid activity can only be induced by non-NMDA receptors [kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)]. The reticulospinal and sensory inputs are known to act via both NMDA and non-NMDA receptors, but it is unclear how these inputs can provide an appropriate control of the locomotor rate. We have examined the effects of different types of excitatory synaptic input to neurons of the locomotor network with the use of a computer-simulated electrical neuron model, with Na+, K+, Ca(2+)-dependent K+ channels, and with inherent oscillatory properties linked to the NMDA conductance. Synapses were modeled as a modulated ionic conductance in the membrane of the postsynaptic cell comprising a voltage-dependent NMDA component (Na+, K+, Ca2+ conductances) of long duration, and/or a non-NMDA component (Na+, K+ conductance) of short duration. 2. By using two neurons to drive a postsynaptic cell with non-NMDA-type synapses, a continuous range of firing frequencies could be evoked in the postsynaptic cell, by altering the firing rate of the presynaptic cells. If a single presynaptic neuron was used, there was a tendency toward spike synchronization between the pre- and postsynaptic cells. 3. When a postsynaptic neuron was driven via NMDA synapses, an oscillatory burst activity could be evoked. The rate of the oscillations was, however, little affected by the presynaptic firing rate. When a drive neuron with mixed (NMDA and non-NMDA) synapses was used, the rate of the oscillations could be changed within a limited frequency range by altering the presynaptic firing rate. By adding another larger drive neuron, having a larger rheobase current and mixed synapses with smaller relative NMDA components, the frequency range of the postsynaptic oscillations could be markedly increased. The frequency range depended on the parameters selected for each of the two types of mixed synapses. 4. A small rhythm-generating neuronal network, comprising six cells connected as the principal interneurons of the lamprey spinal locomotor network, was used to test the role of a tonic NMDA and non-NMDA receptor activation to drive the network and produce bursting.(ABSTRACT TRUNCATED AT 400 WORDS)