The synapses of Theseus

The Greek hero Theseus had a ship that was used in an annual ceremony. As the ship aged, the planks would slowly rot and were, over the years, replaced. Eventually, after many years, every one of the planks was replaced. Is it the same ship? This philosophical problem plagued the Greeks, and highlights the tension between stability and change.

This problem reappears in neurobiology in many ways. Neurons must have some stability or processing information becomes impossible. Neurons must be able to change or learning becomes impossible.

Neurons could change in many ways during learning, but most of the attention has focused on the synapse, the gap between neurons where chemicals flit from one cell to the next, and cause a change in the target cell. We know synapses can change during learning, but is that the only time they change?

Answering this question is a problem of resolution. You need lots of detail tracked very closely for a long time. Trying to do this in an animal is not going to happen, so Minerbi and colleagues used neurons in culture instead. One of the tricky bits is to keep the cells alive on a microscope slide! This required keeping the slide heated, blowing sterile air through it, and several other things to keep the neurons happy during the days the experiments ran.

The slides also contained a series of electrodes, so that they could record the action potentials of neurons. I am still trying to wrap my head around the “wires” hooking up the electrodes. They’re tiny and transparent. What neurobiologist knew indium tin oxide existed, never mind that it was transparent and conducted electricity?

To see the shape of the synapses, Minerbi and coworkers tagged a protein found mainly in the receiving side of synapses with a fluorescent marker. So now they've got activity, synapse shape, and a system that lets them scan many different areas in their culture every half hour for days.

As expected, when neurons spike a lot, the synapses change. You’d be concerned if they didn’t. interestingly, the small ones tended to get bigger, and the big ones tended to get smaller. They suggest there is perhaps some sort of optimal size the synapses are converging on.

To test what happens when there is no activity, they tossed in a little tetrodotoxin, also known as pufferfish poison. It’s poison because it stops action potentials cold. The authors still saw the synapses changing, although some of the patterns were different. The whole “big get smaller and small get bigger” pattern wasn’t seen. The key point is that the synapses didn’t just stay, as it were, “frozen.”

One issue is that these neurons were cultured from newborn rats, which is obviously a time when brains are still undergoing a lot of developmental changes. It would be very interesting to see if more mature neurons were more stable, or changed in different ways in response to activity, or lack thereof.

There’s more to this paper, but it involves substantial mathematical modeling, and it starts to pull me out of ability to comment coherently. Lots of very interesting data here in a real technical tour de force.

Reference

Amir Minerbi, Roni Kahana, Larissa Goldfeld, Maya Kaufman, Shimon Marom, Noam E. Ziv (2009). Long-Term Relationships between Synaptic Tenacity, Synaptic Remodeling, and Network Activity PLoS Biology, 7 (6)