Recording electrical signals from inside a neuron in the living brain can reveal a great deal of information about that neuron’s function and how it coordinates with other cells in the brain. However, performing this kind of recording is extremely difficult. To make this technique more widely available, MIT engineers have now devised a way to automate the process, using a computer algorithm that analyses microscope images and guides a robotic arm to the target cell.
This technology could allow more scientists to study single neurons and learn how they interact with other cells to enable cognition, sensory perception, and other brain functions. Researchers could also use it to learn more about how neural circuits are affected by brain disorders.
“Knowing how neurons communicate is fundamental to basic and clinical neuroscience. Our hope is this technology will allow you to look at what’s happening inside a cell, in terms of neural computation, or in a disease state,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, and a member of MIT’s Media Lab and McGovern Institute for Brain Research.
Boyden is the senior author of the paper, which appears in Neuron. The paper’s lead author is MIT graduate student Ho-Jun Suk.
This technology paves the way for in-depth studies of the behaviour of specific neurons, which could shed light on both their normal functions and how they go awry in diseases such as Alzheimer’s or schizophrenia.
For example, the interneurons that the researchers studied in this paper have been previously linked with Alzheimer’s. In a recent study of mice, led by Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory, and conducted in collaboration with Boyden, it was reported that inducing a specific frequency of brain wave oscillation in interneurons in the hippocampus could help to clear amyloid plaques similar to those found in Alzheimer’s patients.
“You really would love to know what’s happening in those cells,” Boyden says. “Are they signaling to specific downstream cells, which then contribute to the therapeutic result? The brain is a circuit, and to understand how a circuit works, you have to be able to monitor the components of the circuit while they are in action.”
This technique could also enable studies of fundamental questions in neuroscience, such as how individual neurons interact with each other as the brain makes a decision or recalls a memory.
Bernardo Sabatini, a professor of neurobiology at Harvard Medical School, says he is interested in adapting this technique to use in his lab, where students spend a great deal of time recording electrical activity from neurons growing in a lab dish.
“It’s silly to have amazingly intelligent students doing tedious tasks that could be done by robots,” says Sabatini, who was not involved in this study. “I would be happy to have robots do more of the experimentation so we can focus on the design and interpretation of the experiments.”
To help other labs adopt the new technology, the researchers plan to put the details of their approach on their web site, autopatcher.org.
Other co-authors include Ingrid van Welie, Suhasa Kodandaramaiah, and Brian Allen. The research was funded by Jeremy and Joyce Wertheimer, the National Institutes of Health (including the NIH Single Cell Initiative and the NIH Director’s Pioneer Award), the HHMI-Simons Faculty Scholars Program, and the New York Stem Cell Foundation-Robertson Award.