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New microscopy techniques capture brain-wide sensory processing

In its 2014 Life Sciences Call ‘Imaging’, the Vienna Science and Technology Fund (WWTF) aims to stimulate innovative biological and biomedical applications of novel imaging technologies and to foster collaboration between biologists and physicists. Out of the 126 initial proposals, eight were chosen for funding by an international jury.

Among the successful applications is the project ‘Whole brain imaging of decision-making in freely moving C. elegans’, by neurobiologist Manuel Zimmer and physicist Alipasha Vaziri. Both scientists are Group Leaders at the Research Institute of Molecular Pathology (IMP) in Vienna (Alipasha Vaziri is also affiliated with the University of Vienna). Their project will address the question of how the nervous system processes information – from the initial sensory input to the resulting behavior.

Sensory to behavior transformations performed by the brain involve perception, decision making, and motor execution, all of which take place across different brain regions, involving cross talk and feedback between them. These mechanisms serve to continuously update brain circuitry for optimal behavioral performance. To gain full understanding of these processes, it would be desirable to track the flow of information across the entire brain with high resolution and in real time – ideally in animals that are free to move and decide. In most cases, however, such a holistic experimental approach is impeded by the sheer size and complexity of brains.

The teams of Manuel Zimmer and Alipasha Vaziri have therefore chosen a simple organism, the nematode C. elegans, as a model for their research. The tiny worm’s nervous system is made up of just 302 cells but still shares basic characteristics with the mammalian brain. Zimmer and Vaziri recently published two new approaches that enable them to perform near simultaneous recording of the activity of almost all individual neurons in the worm.

So far, these measurements were only possible in paralyzed animals. The newly funded project will now combine innovative microscopy and behavioral tracking techniques for high-resolution brain-wide imaging of animals that are allowed to move freely. Employing the new technique, it will be possible for the first time to capture a complete view of brain-wide sensory to behavior information flow at single cell resolution while an animal performs navigational decision making. The ultimate goal to reach a comprehensive understanding of the brain’s operational principles will thus become one step closer.