Variability of quantal NMDA to AMPA current ratio in nucleus tractus solitarii neurons

The ratio between AMPA and NMDA receptors is a key factor governing integrative and plastic properties of excitatory glutamatergic synapses. To determine whether the respective proportions of AMPA and NMDA receptors are similar or vary across a neuron's synapse, we analyzed the variability of NMDA and AMPA currents in quantal responses recorded from neurons located in the nucleus tractus solitarii. We found that the average NMDA to AMPA current ratio strongly differed between recorded neurons and that most of the intra-neuronal current ratio variability was attributable to fluctuations in NMDA current. We next performed computer simulations with a Monte Carlo model of a glutamatergic synapse to estimate the part of AMPA and NMDA currents fluctuations induced by stochastic factors. We found that NMDA current variability mainly resulted from strong channel noise with few influence of release variations. On the contrary, partly because of the presence of subconductance states, AMPA receptor channel noise was low and AMPA current fluctuations tightly reflected changes in the amount of glutamate released. We next showed that these two factors, channel noise and fluctuations in glutamate release, were sufficient to explain the observed variability of the NMDA to AMPA current ratio in quantal events recorded from the same neuron. We therefore concluded that the proportion of AMPA and NMDA receptors was similar, or roughly similar, across synapses onto the same target cell.