Researchers from the Janelia Farm Research Campus at the Howard Hughes Medical Institute (HHMI) have created a new technique to view neurological activity in a Drosophila brain as it moves freely. Certain cells in the fly’s brain amplify their response to visual motion when the fly walks. Imaging this activity in real time has never been done in the Drosophila and promises to help uncover the general principles of neurological circuit function that are relevant to mammalian higher sensory motor processing.
The fly-on-a-ball technology has been a behavioral research standard for 40 years, and works by confining an insect’s movement to the surface of a suspended ball. Its behavior can then be studied under controlled sensory conditions. But unlike larger animals, a fly walking on a ball was not a conducive setup for experiments in sophisticated sensory imaging.
The HHMI group, led by Vivek Jayaraman, overcame this limitation by adapting two-photon imaging—a method which provides high depth view of living tissue typically use with organisms contorted into place—to flies in motion (1). The group constructed a special holding chamber which allowed the fly’s brain to be immersed in artificial brain fluid for imaging while its legs and wings were kept dry. The setup also effectively decoupled the fly’s own motion from the visual motion it sees, allowing them to test neural responses to the same visual motion under different walking conditions.
“What my post-doc Johannes Seelig did which was a little bit McGyver was fixing the chamber,” Vivek told BioTechniques. “Not quite chewing gum, but it did require a few tricks.”
Using two-photon imaging to monitor for intracellular changes in calcium that signify neuron activity, the researchers observed the activity of motion-sensitive lobula plate tangential cells (LPTCs). His post-doctoral fellow Eugenia Chiappe then found that horizontal system (HS) neurons—a subset of LPTCs that play a key role in the visual motor pathways of insects—showed increased calcium transients when responding to visual motion when the fly itself was moving.
“Essentially, Eugenia found that the tuning of the same neurons changes and they respond more strongly to faster visual motion when the fly is walking,” said Vivek.
By using Drosophila as their model, Vivek’s group can see and manipulate the organism’s neural circuits. Larger organisms—such as primates—are valuable for studies invested in cognition but do not easily permit tinkering such as the identification, labeling, sensing and manipulation of individual classes of neurons.
“You can build a picture of what you think is happening and you can test these models. That’s a huge motivating factor,” said Vivek. “The most appealing thing is we can go beyond opaque words to describe what we find. We can really observe basic processes that enable the phenomenology we see,” he said of the team’s technique.
While the mechanics of a fly and a primate are different, there may be similar broad principles at work in neural circuits across species. The key is starting small. “We can get the mechanisms of principles that are hard to study in larger organisms,” he said.
In a separate study conducted recently by researchers in Michael Stryker’s laboratory at University of California, San Francisco, the visual neurons of mice were shown to respond differently to the same stimuli when the rodent was walking (2).
“Already we have a link in that neurons in the rodent primary visual cortex seem to respond more to visual input when the animal is walking. It seems to be a common principle that responses of an animal’s visual system are dependent on the animal’s motion state,” said Vivek.
The next step for the team will be to study the central complex, a region thought to underlie higher sensorimotor processing in the fly, looking for clues about how learned oriented behaviors arise. “We have an opportunity to discover basic sensorimotor principles that are common to more than just insects or flies,” said Vivek.
1. Eugenia Chiappe, M., J.D. Seelig, M.B. Reiser, and V. Jayaraman. 2010. Walking modulates speed sensitivity in Drosophila motion vision. Current Biology 20:R679-80.
2. Niell, C.M. and M.P. Stryker. 2010. Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65: 472-479.