Comparing human brains (and to a lesser extent all primate brains) to other animals like the mouse, we have many more, much bigger and much more complex astrocytes. Astrocytes have contributed to our larger brain by an order of magnitude more than neurons have. Astrocytes make contact and ‘surround’ synapses; one human astrocyte can encompasses 2 million synapses. They seem to look over the communication between neurons and are involved in long-term potentiation, the first stage of memory and learning. They release TNFalpha which increases the strength of synaptic transmissions. One human astrocyte makes contact with more synapses because of their bigger size and longer thin fibrils reaching to more distant synapses.
Astrocytes communicate with neighbouring astrocytes through movement of calcium ions. Waves of calcium pass through groups of astrocytes. These waves are faster and more extensive in human astrocytes. So as a communicating group, astrocytes affect the electrical and chemical environment of neuron synapses. And human astrocytes appear to do it better.
So… clever idea – put human astrocytes in mice and see what happens. Xiaoning Han et al (citation below) injected new born mice with human cells destined to become astrocytes. The human cells florished at the expense of the mouse ones, migrated to the right places and intergrated with each other and the mouse astrocytes. But they were the size and complexity that they would have been in a human brain. So the mice ended up with the more numerous, bigger and more connected human astrocytes amongst their own mouse ones. Like in humans the calcium waves were faster and the TNFalpha more potent. That this procedure worked as well as it did is a bit of a surprise.
When the mice were adult they were tested against control mice that had transplants of mouse rather than human astrocytes. The human astrocytes gave significantly better memories and learning. When the TNFalpha was disrupted, the human astrocyte advantage was much reduced.
What can be done with this development?
First, we could think of the brain differently. Last year, I posted what if? One of the imagined shifts of viewpoint was:
“There is a trickle of new results about the function of glial cells (those ignored cells that outnumber the neurons by factors like 10). What if: more of less all the work in the brain was actually done by very local groups of glial cells and neurons functioned like a kind of telephone system between groups of glia.”
Second, we can stop taking the simpler computer metaphors, ones containing only neurons and weighted connections, as a reasonably detailed model of the brain. “We are our connectome” also becomes less believable. The Neuron Theory has taken a little knock – there is more to brain processing then neurons firing.
Thirdly, these mice can be used to study astrocytes using procedures that are possible in animals but not humans.
Fourthly, they would be good systems to study diseases of the astrocytes and even to show whether a disease involves astrocytes or not.
Here is the paper’s summary:
Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca 2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.
Han, X., Chen, M., Wang, F., Windrem, M., Wang, S., Shanz, S., Xu, Q., Oberheim, N., Bekar, L., Betstadt, S., Silva, A., Takano, T., Goldman, S., & Nedergaard, M. (2013). Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice Cell Stem Cell, 12 (3), 342-353 DOI: 10.1016/j.stem.2012.12.015