New imaging techniques to reveal secrets of the brain

Every second our brains register billions of new impressions. Incomprehensible amounts of information are transported along nerve paths. Techniques are now being developed to image how nerve cells in the brain communicate and set up networks. The goal is to present new findings about the genesis of diseases like Parkinson’s and Alzheimer’s.

Andrew Ewing

Professor of analytical chemistry

Wallenberg Scholar 

University of Gothenburg and Chalmers University of Technology

Research field:
The focus is on understanding how signal substances are used to communicate at the cellular and subcellular level. 

This research is being driven by Andrew Ewing, an American researcher who has crossed the Atlantic and become professor of analytical chemistry at University of Gothenburg and Chalmers University of Technology. He has now been named a Wallenberg Scholar, and the associated grant will enable him to carry his research even further.

“We are hoping for research findings that can help us better understand learning and memory, but also findings that can enhance our knowledge of neurodegenerative diseases like Parkinson’s and Alzheimer’s,” says Andrew Ewing.

The research is being carried out at a new center of competence for chemical imaging, established jointly by University of Gothenburg and Chalmers. Andrew Ewing shows off his laboratory, which boasts some brand new equipment. Every square centimeter of the basement premises is utilized. This research is heavy on technology. Among other equipment, there are five mass spectrometers, where researchers separate molecules from each other and analyze their mass and charge. They can study the molecular composition of various areas of nerve cells. All the work is done at the micro and nano levels, and they deal with parts of cells that are about a hundred times smaller than the thickness of a strand of hair.

Filming individual cells

The adult human brain contains more than 100 billion cells. It may seem daunting to try to find order in this jumble. In order to perform electrochemical analyses, the scientists first need to figure out where in the brain the measurements are to be made.

Fruit flies are used in many research projects as a model system. This is also the case here, where the flies are first placed on ice to be numbed before fluorescent proteins are introduced into their brains, using a technique where the gene for green fluorescent protein is attached to a gene that codes for a protein of interest. In a fluorescence microscope the researchers can then visualize the brain structure and gain knowledge of where the measurements are to be undertaken.
One entirely new technique also involves placing electrodes that are 10 by 10 nanometers in size within an area of a few micrometers in order to create images of the chemical dynamics of individual cells. The plan is to successively increase the scale.

“Thus far we have reached 16 electrodes and are now working toward the 100 we planned. The dream is ultimately to achieve electrodes of 64 by 64 nanometers, thereby establishing 4,096 measuring points. That would yield sufficiently high resolution for us to use technology commonly used in video cameras to film the electromagnetic process in individual cells and cellular networks,” says Andrew Ewing.

Once the technology has matured, it will be possible to apply it not only to basic studies of individual cells, but also to use it in screening experiments to examine pathogenic mechanisms, neurological studies of how learning and memory work, and studies of the effects of new pharmaceuticals on individual cells and cellular networks.

Understanding communication in the brain

One particular question that interests Andrew Ewing is to grasp how signal substances are released in the brain. Signal molecules are stored in the synapse in tiny vesicles, which are then emptied into the synapse and fasten onto receptor proteins on the side of the receptor cell. These vesicles can contain several kinds of signal molecules.

“We want to track the vesicles and take images of how they function. Thus far we haven’t managed to achieve sufficiently high resolution. Among other things, we want to study how membranes function, what goes on when they release 30 to 40 percent of their contents and exchange certain lipids and proteins. It’s a highly energy-efficient and exciting system.”

Among other questions, these scientists are targeting what happens with the lipids that are exchanged and whether the lipids have the capacity to affect how much of the signal substances are exchanged. It may even be possible to capture in images how a short-term memory is converted into a long-term memory, and what happens in the brain’s chemistry when a drug is transformed into an addiction. They also wonder whether this knowledge, in turn, could make it possible to control the transport of signal substances, which might lead to new pharmaceuticals and improved methods of treatment in the future.

"It was wonderful news.
I don’t usually do cartwheels down the hall, but that’s what I did. As far as I know there’s no research funding like it in the world, and it’s tremendously flattering and gratifying to receive such a no-strings grant from the foremost independent research financier in Sweden."

Aspired to be a veterinarian

Andrew Ewing grew up in the US and dreamed of becoming a veterinarian in high school. He worked part-time at an animal clinic, doing everything from cleaning cages to assisting in operations. But in college he discovered what a truly exciting subject chemistry is, once you get past the elementary stage (he’s quick to add). He embarked on doctoral studies and published 14 scientific articles while still a PhD student.

“At the time the focus was on dopamine, and I discovered a few new things, including aspects of how dopamine is transported to membranes in cells. When my little brother died of leukemia in 1996, I considered switching to cancer research, but I came to my senses. I persuaded myself that it’s better to continue in a field I really know and burn for, and I haven’t regretted the decision.”

Understanding the brain has always been an important driving force. Next to his daughter’s colorful drawings above his desk, there’s a note that says: "What is the vision?" This is an exhortation, something researchers must always bear in mind, according Andrew Ewing.

“We have to have bold objectives, and think into the future. What is the vision behind my research, what is important, and why am I doing this work – these are questions you have to ask yourself every once in a while. And even though work in the lab is valuable, you have to take the time simply to read and ponder the bigger picture now and then. That’s what underpins successful research.”

Text Nils Johan Tjärnlund
Translation Donald S. MacQueen
Photo Magnus Bergström

Synapses in the brain

The vision is to attain a considerably more detailed understanding of how the contact points for cells, so-called synapses, function. In the synapse, signal substances are released by the signaling nerve cell. In other words, the electrical signal is converted to a chemical signal. The receptor cell gets the message and interprets it back into an electrical signal. 
This elegant communication system is comprehensive.

Every nerve cell can contain some 10,000 synapses from hundreds of different cells. The more often a signal path is used, the more synapses will be created. It can be likened to a regular road where the wheel ruts get deeper and deeper. Over time it gets easier and easier to send signals via a certain nerve path. This is how behaviors and memories are created, but also various types of addictions.