Bone and Blood – Of mice and men, part one

Kim Le

Kim Le

Networking has gotten a bit easier for me, as I’ve gotten older and less bothered with social mores and feeling self-conscious. These days I’ve given up any pretense of being a normal person at a party, dispensing quickly with introductory chit chat – “So like, what’s your day job?” – and instead, elect to go right into pontificating about shuttered malls and the death of the middle class. (Okay, so maybe this is why I don’t often get invited to parties.) Many politely excuse themselves and drift to a far away corner, but this tactic has successfully connected me to several kindred souls.

This is how I met Simon, a postdoctoral researcher, whose day job I did eventually learn; it involves installing windows into the brains of mice, opening up a view to help better understand the decay of human minds. Intrigued, I made an appointment to further chat with him. We grabbed some beers at an Irish pub and talked about the path that led him to his current work.

As a young nerd, he’d been inspired to study cell biology by the Hulk. During the course of his undergraduate studies, he couldn’t find work in any labs that would let him expose himself to high level gamma radiation. Instead, he wound up in a neuroscience lab, investigating pain signals.

Here, in the pain lab, he came to the realization that “neurons are the coolest of all cells.” Simon and his colleagues studied the secrets of the spinal cord, which functions as a bit of a mini-brain. The spinal cord takes in a massive amount of information (touch, sight, sound) gleaned from various parts of the body and integrates it all in a sensible, coherent fashion, resulting in balance. This enables us to perform feats such as walking around without knocking into things (well, most of the time for some of us. Ahem).

All this was indeed quite fascinating, but Simon was not quite content with pursuing this – he wanted to get even closer to the source of knowledge, the brain itself. He moved on to study brain structures, how they change during the process of learning, aging and after acquiring cognitive damage. Researchers actually learn a lot about how the brain works by examining brains that have stopped working; in engineering terms, this is called “failure analysis.” This led Simon to his current area of research, studying how the brain changes in those with Alzheimer’s.

What tangible changes are happening to your brain, your synapses and neurons, as your memories slough off into the ether, and elements of your personality disintegrate? What happens to the very basic fundamental building blocks of what makes you you? What causes these plaques and tangles to form and accumulate; what precipitates these mini-disasters in your head?

Delving ever further into the inner workings of the degenerating mind, Simon began talking to systems neuroscientists, who are considered by many to be the cool new kids on the block with regard to brain research. Instead of messing about with isolated cell cultures in petri dishes, systems neuroscientists look at the way the brain and its subunits work (or don’t) as a whole. One little lonesome neuron by its dorksome self is fairly useless, if it’s just lurking in a corner refusing to talk to anyone. Get a bunch of neurons together, though, and now you have a party. Working in concert, these neural networks can make things happen; the possibilities are endless (kegstands! riots! couches aflame!).

Until relatively recently, studying the workings of these neural networks to any fine degree of precision had been a bit of a challenge. There are a bewildering variety of neurons of different shapes, functions and name lengths. How to pick out just one type of neuron out of the many hundreds of shapes in the crowd? How to study just those specific neurons belonging to this group, without messing with any of the others?

Enter the advent of optogenetics, a rather sexy new technology that essentially enables researchers to control brain cells with light. How it works, for dummies and written by a dummy: take a specific gene from a certain type of pond algae, which naturally gravitates towards light. Load that gene onto a virus, and send that virus after the type of neuron you are wanting to investigate. Rig it so that the virus infects only those specific neurons with the gene from that pond algae, and then et voila – if you want just only those neurons to fire, just shine a light on them. Of course, the light actually has to reach the neurons, so you’ll probably need to install a window in the neuron owner’s cranium*. You can also load a gene that makes a type of neuron become fluorescent when it fires, in essence, causing a literal light bulb go off in a mouse’s head whenever it thinks. You can watch the mouse learn a new task, and actually see that learning take place as shining neurons reconfigure themselves.


(Optogenetics is pretty much tailor-made for superhero / villain origin story material).

The brain is wonderfully adaptable and flexible, which is great for us brain-havers, but makes it difficult to know when things have irreversibly broken. By the time you show symptoms of Alzheimer’s, most of the brain’s degeneration has already taken place. Simon thinks systems neuroscience tools can be used to help detect changes early. We might be able to record brain activity and be alert to any distinct off “notes” or deviations in pattern, making treatment and intervention strategies a lot more effective.

As Simon spoke, I sat and typed up notes, enthralled by all the possibilities that I had now learned. (Had my brain cells been infected with that pond scum gene, I’d have shone like a Christmas tree, I’m sure.) Now, Simon and I are obviously very different people with varying levels of usefulness. He happens to be an actual scientist working to better the world; I write columns on the Internet about weird museums. But I’d like to flatter myself in thinking that we share a basic approach to the world. I feel like we’re both looking around in unexpected places to try and find the invisible strings – the bones and sinew that hold things together.

Stay tuned for next column, which may or may not entail a potential field trip?

* Note: all animal research conducted complies with the guidelines set out by his university’s Institutional Review Board, as well as Institutional Animal Care and Use Committee. Please do not try and liberate these mice, activists. The city rats will likely beat them up and bash in their head-windows.

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Kim Le is a writer and shiftless gadabout who hails from the distant wheat fields of Kansas. Obsessions include sustainability, yurts and extreme DIY. Also, she makes sculptures out of food, mostly potatoes. She never updates her blog at http://badmetaphor.net.

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