Nerve cell imaging in freely swimming fish

HFSP Project Grant for advances in optical microscopy

We sense something and then react accordingly. It remains largely unknown, however, how the brain integrates sensory information to generate an appropriate behavioral response. A team of scientists from the Max Planck Institute of Neurobiology in Martinsried, the Charité Berlin and the University of North Carolina now aim to advance optical microscopy in such a way, that it becomes possible to image the activity of individual nerve cells in freely swimming fish. The aim is to boost the research on how sensory information leads to behavioral responses. The Human Frontier Science Program (HFSP) supports the project with a Research Grant.

To understand how the brain processes sensory information and initiates a respective behavioral response is a central goal of systems neuroscience. However, in order to investigate this process, it is necessary to image those nerve cells in the network that become active when the organism senses something and reacts accordingly. For a long time, this seemed impossible. Recent advances in genetics, optogenetics and microscopy, make it now possible to both see nerve cells lighting up when they become active and to change the cells' activity by shining light on them.

Zebrafish larvae, which are small vertebrates, have become a very promising model for this non-invasive research: they are almost completely transparent and the brains of the roughly five millimeters long fish are so small, that the majority of neurons can be imaged simultaneously with cellular resolution. image the neuronal dynamics in the brains of zebrafish larvae – while the five-millimeter-long fish are freely moving about.

In order to record the nerve cell activity, the head of the fish larva is temporarily fixed in a gel. Scientists are then able to see through the microscope which nerve cells are active when the fish sees a stimulus and reacts to it. The head-fixation has little effect on the fish larvae, which freely swim about after the observation. However, the virtual reality the fish see during the experiment is no replacement for a real environment. This fact poses a barrier to progress in this research area.

Ruben Portugues, Research Group Leader at the Max Planck Institute of Neurobiology and his colleagues, Benjamin Judkewitz and Spencer Smith, aim to breach this research limitation. In their HFSP supported project, they will pool their collective expertise in optical systems design, wavefront-¬shaping, electrical engineering, and zebrafish neuroscience to image nerve cell activity with single cell resolution in freely swimming fish. The project runs for three years and will support each team with approximately $300,000.