High synaptic threshold for dendritic 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 dendrites to generate NMDA-receptor-dependent spikes (NMDA spikes). Using dendritic glutamate iontophoresis, as well as local dendritic synaptic stimulation, we find that human layer 2/3 pyramidal neurons can generate dendritic NMDA spikes. The capacity to evoke NMDA spikes in human neurons, however, was significantly reduced compared with that in rodents. Simulations in morphologically realistic and simplified models indicated that human neurons have a higher synaptic threshold for NMDA spike generation primarily due to the wider diameter of their dendrites. In summary, we find reduced NMDA spike generation in human compared with rodent layer 2/3 pyramidal neurons and provide evidence that this is due to the wider diameter of human dendrites. [Display omitted] •Human pyramidal neurons generate NMDA-receptor-dependent dendritic spikes (NMDA spikes)•NMDA spike generation is reduced in human compared with rodent pyramidal neurons•Differences in NMDA spike generation were reproduced in human and rodent models•The wider diameter of human dendrites reduces NMDA spike generation in human neurons Testa-Silva et al. investigate the capacity of human cortical pyramidal neurons to generate NMDA-receptor-dependent dendritic spikes and compare that with rodent neurons. They find that NMDA spike generation is reduced in human neurons and provide evidence that this is due to the wider diameter of human dendrites.