Genetics meets physiology: Research in a minute brain

Neurobiologists can now combine genetic and physiological methods in the tiny brain of the fruit fly.

March 18, 2008

What's the function of a single nerve cell and how do cells interact with each other? Scientists at the Max Planck Institute of Neurobiology investigate these questions in the brain of an animal which is smaller than a pinhead. In the fruit fly Drosophila, the scientists are now able to combine genetic and physiological methods to investigate the fly visual system. This new approach should greatly enhance our knowledge about the function and wiring of nerve cells.

The human brain consists of approximately a hundred billion nerve cells and trillions of cell contacts. The activity and interplay of these cells control every single reaction and even the minutest of movements. Unraveling how this is achieved is one of the major challenges of modern neurobiology.

Flies: Masters of visual perception

Moving stripes stimulate the optic nerve cells in the fruit fly brain while electrodes record the cells' electrical responses.

A first step towards understanding such complex nervous systems is to look at something a bit simpler. Scientists choose model systems, which differ in dependence of the questions considered. The processing of optical information, for example, is investigated at the Max Planck Institute of Neurobiology in the brain of the fly. In comparison to a vertebrate brain is the brain of a fly a much simpler structure, containing fewer nerve cells by several orders of magnitude. This eases the investigation of interactions between cells. In addition to this benefit, fly nerve cells are extremely efficient in processing optical information. The blow fly, for example, would see a movie with 100 frames per second as separate pictures, whereas humans already miss the dark breaks at 24 frames per second. Moreover, the fly's brain needs a mere 60 nerve cells to process this rapid visual input – with ample time to initiate escape maneuvers even while flying at a speed of 10 km/h.

Major improvement in fly research

The now possible combination of this method with the genetic manipulation of target cells promotes the investigation of single cells and cell network function. Right: A single cell from the fruit fly's flight control center.

So far, the cell connections of the fly optical system were investigated mainly in the blow fly. The fly would see stripes moving past its eyes in a sort of "fly cinema" (see figure below). This would trigger an optic response, which could then be recorded with the aid of electrodes inserted into single nerve cells. Such measurements already confirmed the predictions of mathematical models on how flies perceive motion. "However, even after 40 years of research, we still don't know what really happens at the level of the involved cells" explains Maximilian Jösch. The young scientist now succeeded in recording the cells' electrical responses also in the brain of the fruit fly Drosophila. At first, this sounds mainly crazy: An entire fruit fly is about as large as the brain of a blow fly; to insert electrodes into single nerve cells in this minute brain seems hard. Well, it is. However, it also opens up exciting research abilities. The intensive Drosophila research of the past decade(s) allows researchers to choose from a wealth of genetic manipulation methods for this fly. One possibility is to fluorescently mark single nerve cells, which facilitates investigations. Even more thrilling is the possibility to utilize temperature sensitive mutations. A slight rise in temperature can temporarily deactivate the synapses of a specific nerve cell. Now, the effect of the target cell's removal from the cell network can finally be investigated through the use of electrodes.

Improvement in comprehension of brain functions

"Up to now, scientists investigating the brain functions of Drosophila would knock out certain cells and then scrutinize for any changes in the fly's behavior" explains Alexander Borst, whose department investigates the fly visual system. "However, which changes in the nerve cells induced the observed behavioral changes remained arcane." Such underlying changes in the electrical wiring between nerve cells could be detected by the blow fly research, which lacks the possibilities of selective genetic manipulations. Bringing the blow fly research now into the fruit fly, enabling the new combination of genetic and physiological methods, is a major step forward. This should not only enhance our comprehension of the fly's motion vision but also improve our understanding of the function and wiring of nerve cells in general.

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