Tuesday, 15 October 2013

Human brain cells make mice learn faster

Image by Coxy

If you're reading this blog, you're smarter than a mouse. And that's not because this blog is so very highbrow, whereas mice only read Heat magazine. Mice can't read, silly. But what is it that makes humans more intelligent than other animals?

If your response was "brain size", you're only partly right. Because for brains, like other body parts, size isn't everything. For example, sperm whales' brains are roughly five times more massive than humans', but sperm whales are easily beaten at backgammon.

So what else is important?

The answer is that we're still finding out. You might not know that brains are made up of both neurons - the cells that are coupled to each other and to nerves in the rest of the body via electrical junctions called synapses, and which are what most people think of when they think of brains - and other cell types, collectively called glia. Until the past decade or so, most scientists thought that only neurons were important to brains' ability to carry out the things that make having one desirable - sensing, learning, thinking, planning, acting, etc. But more and more they are coming to appreciate the large part that glia play in the brain's activity.

A paper I recently came across published by Xiaoning Han et al in Cell Stem Cell earlier this year adds to that growing appreciation. This group isolated immature human glial cells and then transplanted them into the brains of young mice whose immune systems had been weakened to prevent the cells being rejected. The researchers had labelled the human cells so that they would be able to visualise them later on, and when they did so after a number of months they found that the human cells had integrated nicely with the mice's own brain cells.

But in integrating, the human cells had retained their human shapes and characteristics. Some of the immature cells matured into a glial subtype called astrocytes, and human astrocytes are larger and more complex than their mouse counterparts.

Why is this interesting (and very cool)? Because when the researchers examined the mice's ability to learn by challenging them with a variety of well-established tests, like escaping from a maze, the mice that had received human cells learnt more quickly than control mice.

Those controls included mice that had had mouse glial precursors implanted instead of human cells, so the effect was nothing to do with the human-mouse chimeras having bigger brains. When the researchers delved deeper using a variety of biochemical techniques, they were able to narrow down the likely cause. It seems that the human cells strengthened synaptic signalling in the mouse brains by releasing a molecule that, through one or more downstream cascades, resulted in a neurotransmitter receptor subunit being modified by the addition of a small chemical group, facilitating insertion of the receptor into the synaptic membrane.

Discussing their findings, Han et al say 'These observations strongly support the notion that the evolution of human neural processing ... in part may reflect the course of astrocytic evolution.'

It does seem curious that this increased ability of the chimeras to learn, which would surely convey a substantial survival advantage, appears to be due simply to the phosphorylation of one amino acid in one receptor subunit. If I were a respected science journalist and not just an unknown hobbyist, I'd be asking the group whether they had any speculations on what might prevent mice or any other animals evolving some means of gluing that phosphate on - or doing some equivalent thing - and getting the extra smarts. I suppose it's more the ability to carry this modification out in a coordinated way over a large scale that is important, but still...

The full reference is below. The journal website says nothing about the paper being open-access, but for the moment at least non-subscribers can access the PDF here.

Han X, Chen M, Wang F et al (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12(3):342-53