High Synaptic Threshold for NMDA Spike Generation in Human Layer 2/3 Pyramidal Neurons

Neurons receive synaptic input primarily onto their dendrites. While we know much about the electrical properties of dendrites in rodents, we have only just started to describe their properties in the human brain. Here we investigate the capacity of human neurons to generate NMDA spikes. We find that dendritic iontophoresis of glutamate, as well as local dendritic synaptic stimulation, can evoke NMDA spikes in dendrites of human layer 2/3 pyramidal neurons. However, the capacity to evoke NMDA spikes in human neurons was significantly reduced compared to that in rodent neurons. Simulations in morphologically realistic and simplified models indicated that human neurons have a higher synaptic threshold for NMDA spike generation primarily due to the larger diameter of human dendrites. In summary, we find reduced NMDA spike generation in human compared to rodent layer 2/3 pyramidal neurons which is likely a direct result of the wider diameter of human dendrites.