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Human and mouse neurons

Finally, our article on human and mouse neurons has been published! The popular science article in Russian could be found here. The picture above shows the neurons of a human and a mouse. Human and mouse neurons are similar overall, but they also have substantial differences. For example, human neurons are bigger and have more branches. Comparing human and mouse neurons allows us to learn about the human brain. In particular, the overall structure of mammalian cortex is very similar between the mouse and human.

Nevertheless, if the mouse and human brain look so similar, why are mice unable to play the violin or make the scientific discoveries? In other words, what makes humans special compared to our fellow mammals?

We do not have a good answer to this complex question, especially because it likely has multiple answers from different domains of knowledge. However, at the Allen Institute, we aim to answer at least some parts of this big question. The volume of the human brain, as well as the volume of the cortex area, have substantially increased in humans over the course of evolution. For example, for the last 125 million years, the human cortex has increased to be about 1000 times the size of a mouse cortex. It is reasonable to suspect that human neurons have adapted biologically to these quick evolutionary changes.

To avoid comparing apples to oranges, we compared the properties of only one type of neuron found in both mice and humans – the excitatory pyramidal neurons of layer 2/3. Even when the different sizes of mouse and human brains are considered, these neurons are in the thickest layer of the 6-layer cortex. These neurons have also experienced significant evolutionary divergence since humans and mice last shared a common ancestor. We found that in the membrane of human cortical neurons of layer 2/3 there is a lot of so-called h-current.

H-current is present in multiple neurons of the nervous system and not only in the brain. For example, the cardiomyocytes responsible for generating heartbeats have significant amounts of it. So, what is special about finding h-current in human neurons?

It turns out that human cortical neurons have much more h-current than mouse cortical neurons do. We studied this particular property in single neurons by injecting current into the neurons and quantifying their gene expression. We learned that the h-current is responsible for generating membrane potential oscillations when a human neuron receives an input from its neighboring neurons.

We also found that this current helps the neuron transfer the oscillations of the membrane potential from the dendrites to soma in the range of 4-10 Hz (theta wave). In the hippocampus, this current helps organize memories, but its function in the cortex is not completely clear.

We found that the presences of h-current in human neurons might increase the speed of action potential propagation. One might think that it is a good idea to have large neurons since these neurons would have more synaptic connections, which could potentially yield higher computational power. But everything comes with a cost. Using a computational model based on data from human neurons, we found that the larger the dendritic tree, the slower a signal propagates. It could be that the presence of h-current allows human neurons to transfer information faster, despite their large size.

By comparing the neurons of humans and other animals we hope to gradually understand what makes the human brain special. It could be that the difference between the human brain and mouse brain is similar to the difference between the Cray supercomputer and the Nintendo console. Despite these machines’ overall similarities, the supercomputer has much higher computational power because of its faster processors and larger numbers of elements. These are speculations of course, but appropriate metaphors might help us to understand the brain better.

Thanks for English corrections by Melissa MacEwen

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