Do-It-Yourself Neuroscience

Traditionally, scientific research was the preserve of the wealthy and today the situation is not much different—while researchers need not be rich, almost all of them work in institutional laboratories using equipment that can be very expensive.

Recently, however, a do-it-yourself biology movement has emerged, and a symposium held at the 41^st annual meeting of the Society for Neuroscience in Washington, DC, earlier this month described several innovative projects aimed at minimizing the cost of brain research and making it accessible to everyone.

“If astronomy were like neuroscience, you’d need a Ph.D. to look through a telescope,” says Tim Marzullo, who chaired the symposium. “It’s ridiculous—the technology for recording nervous impulses is 90 years old and there’s no reason why it can’t be brought into schools.”

Marzullo and his colleague Greg Gage are doing just that. Three years ago, they founded Backyard Brains, a small company that manufactures neuroscience kits out of cheap off-the-shelf electronics purchased from outlets such as Radio Shack and distributes them to high schools and colleges, with the help of grant funding from the National Institutes of Health.

“I come from a family of teachers,” says Marzullo. “Backyard Brains came out of my love of neuroscience, education and building things. We see ourselves as part of a broader movement of DIY hackers who are trying to build just-good-enough versions of gear to reduce the barrier to entry.”

A prime example

The symposium itself included a demonstration of how effectively the enterprise can break down these barriers. 11-year-old Ben Robbins of Novi Meadows Middle School in Michigan took to the stage and showed the audience how to use Backyard Brains’ first product, the SpikerBox electrophysiology rig, which consists of two electrodes and a cheap amplifier.

Robbins removed the leg from a cockroach that had been anaesthetized in ice water, pinned the leg to a corkboard with a ground electrode and then impaled it with a recording electrode. He then hooked the SpikerBox to an iPad, which showed waveforms of the spontaneous nervous impulses generated by the leg.

Next, Robbins brushed the bristles on the cockroach leg with a toothpick, observing on the iPad how the amplitude and frequency of the impulses changed according to the pressure applied. Finally, he played some dance music directly through the electrodes, and the cockroach leg began twitching in time with the electrical bursts emitted during the beats. Classical music, favored by his mother, elicited no such response.

Most of the projects described in the symposium use invertebrates as test subjects (like roaches, worms, and crayfish), because they are excellent systems for teaching the principles of cellular and network neuroscience. They are also cheap, easy to maintain, and there are far fewer legal regulations for using them in experiments. When combined with cheap electronics and open-source data acquisition and analysis software, the cost of neurophysiology experiments is drastically reduced.

One example of the free software available for students is Spike Hound, developed by engineer Gus Lott. Spike Hound replaces the need for an A/D integrated microchip board and an oscilloscope for recording differences in electrical potential. It stores data directly to a hard drive, and runs from the computer’s sound card.

Crawdads, and worms

Bruce Johnson, a senior research associate at Cornell University, described his project to help undergraduate students learn about neuroscience through hands-on experience. Together with collaborators from Cornell and Bowdoin College, Johnson has constructed a simple suction electrode that students can use to investigate nerve cell activity in pond snails and crayfish.

Using this scaled down version of equipment that would otherwise cost at least $30,000, the students can learn about how neurons generate and transmit electrical signals. Learning is facilitated by the Crawdad CD-ROM neurophysiology lab manual, which contains instructions and videos, and animated tutorials available on the Cornell University website. Johnson’s faculty workshops are sponsored by the National Science Foundation; his undergraduate course, by the Howard Hughes Medical Institute.

Jeffrey Wilson of Albion College described how he uses earthworms to teach behavioral neuroscience. Students measure worms’ sensitivity to vibration by using a Radio Shack motor attached to a Duplo base plate. Because worms’ axons are large, external electrodes can easily record the nervous impulses they carry. Students can also examine how sensitive worms are to chemical signals by watching them recoil when dead worms are placed near them, and analyze their behavior using tracking software developed at Cornell University.

Cutting-edge science

Stefan Pulver, a postdoctoral fellow in the zoology department at the University of Cambridge, described how he is bringing a state-of-the-art technique called optogenetics into the undergraduate teaching laboratory.

Optogenetics involves using genetic engineering to introduce special proteins into subsets of neurons that render them sensitive to light. This enables the electrical activity of neurons in freely moving animals to be controlled remotely, allowing researchers to manipulate the animal’s behavior with pulses of laser light. Pulver has collaborated with Marzullo and Gage to develop a $200 optogenetics kit for use with transgenic fruit fly larvae expressing the protein Channelrhodopsin in cholinergic neurons that control their muscles.

The control circuit, developed by Gage, fits into a pipette tip box, and is attached to a light source consisting of blue-light-emitting diodes attached to movable arms that can positioned around a dissecting microscope. The circuitry is controlled by an iPad, and produces light strong enough to activate the Channelrhodopsin-expressing cells, allowing students to observe and quantify the behavioral responses.

Using 3-D printing technology, Marzullo and Gage also designed and assembled a micromanipulator, a device students can use to physically interact with a sample under a microscope, helping correctly position electrodes, for example. With it, they can optically stimulate the fruit fly larva while simultaneously recording the activity of its muscles. Under the microscope, the larva can be seen to twitch in response to the pulses of blue light, and students can measure the corresponding increase in muscle activity.

Expanding undergrad science

The number of institutions offering neuroscience undergraduate programs has been increasing steadily over the past 25 years, said Raddy Ramos of the New York College of Osteopathic Medicine during the symposium. Most undergraduate neuroscience programs are found in small institutions such as liberal arts colleges that do not offer postgraduate programs, and there is a growing need for schools to develop their neuroscience coursework.

All of this equipment is well within smallest budget for any institution hoping to develop neuroscience resources. When tied to science writing exercises, quantitative analyses, and class presentations, these experiments bring the lecture material to life, helping students understand more fully the principles of brain function. They also encourage students to generate and test their own hypotheses, increase their interest in neurobiology, and may inspire them to seek out graduate neuroscience programs.

In fact, these projects enable them to get actively involved in scientific research even before they get to college. Students from Melanie Fields’ science class at Sidwell Friends School in the Washington, DC, area have published several academic papers, presented findings at scientific conferences, and taken part in Brain Awareness Week. They also visit public schools in the area to teach other children what they have learnt.

“We’ve been doing research into the jamming avoidance response in weakly electric fish,” says 11^th grader Chris Dock, who attended Fields’ class  two years ago and also spoke during the symposium. “We produce electrical signals then push the frequency up and down to try to determine the threshold of various species. In response, the fish change their own frequency so they don’t get confused and can still be able to locate objects around them.”

All of these low-cost projects are inclusive, catering to differences in students’ interests, skills and styles of learning and expression, and social and ethnic backgrounds. Because the lab teaching and evaluation can be tailored to match student diversity, they are ideal for reaching children who might not otherwise have access to such opportunities.

“We’re from southeastern Michigan,” says Marzullo, “so we’ve gone to Detroit and surrounding areas many times to do workshops and demos. Our first high school demonstration of optogenetics in fruit flies was in an urban school in Detroit, and we’re pretty proud of the fact that they were the first high school kids in the world to see it.”