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This video nicely explains the latest research at caesar. Scientists have developed a small head-mounted microscope that allows access to the inner workings of the brain. The new system enables measurement of activity from neuronal populations located in the deep cortical layer with single-cell resolution, in an animal that is freely behaving. How do nerve cells in the brain process information from the senses and drive complex behaviors? This question has fascinated neuroscientists for many years. In the field of neuroethology, researchers use model organisms like the rat to understand biological processes. Their brain is functional almost identical to the human. In addition, rats perform very well in learning tasks and are well suited to studies of learning and cognition. In the last decade, it has become possible to genetically engineer neurons in animals to produce fluorescence reporters that change their brightness in response to brain activity and then monitor them under a microscope. With this tool at hand, we are getting closer to the central goal of neuroethology: To get a mechanistic understanding of animal behavior at a neural circuit level. To fully answer this question, we have to combine various research tools, such as behavioral experiments and microscopy of brain circuits in the freely moving animal with single cell resolution. To look inside the brain, special microscopes are used that can see through the tissue and observe the neuronal circuits at work. Nonlinear microscopy, such as 2-Photon-Imaging, is well suited for imaging in light-scattering tissue such as the brain. Using a microscope to image neural activity has the advantage of being relatively non-invasive. Mounted outside the brain, it simply sends light into it, in turn receiving the light emitted out of the brain. While conventional microscopes are too heavy to enable functional imaging from freely behaving animals, significant effort has gone into developing head-mounted, miniaturized microscopes over the last years. So far, the state of the art, were so called ‘two-photon fiberscopes’ that are able of measuring brain activity from freely behaving animals with single cell resolution. Unfortunately, still many of the cortical layers remained out of reach. With the use of three-photon imaging one can solve this issue. Due to the light having a longer wavelength, three-photon microscopy is able to penetrate deeper into tissue with reduced out-of-focus excitation. This results in clearer images of structures deep in scattering tissue. In collaboration with Philip Russell’s group at the Max Planck Institute for the Science of Light, the group of Jason Kerr now developed a small head-mounted three-photon microscope, capable of imaging all cortical layers in a freely moving rat. Light is delivered through a custom designed and manufactured glass fiber. The new microscope allows for continuous imaging of activity from neuronal populations, even when the animals runs or jumps, over extended periods of time. Complex behavioral tasks can be performed while the brain is being imaged. They published their results in the Nature Methods article “Three-photon head-mounted microscope for imaging deep cortical layers in freely moving rats”. The fiberscope weighs only 5.0 g, a weight well suited to cortical imaging in rats. It is capable of functionally imaging the majority of the cortical thickness of mature rats. The researchers expect the fiberscope to be widely applicable to behavioral research, as previous microscopes were limited in their imaging depth and unsuitable for use over extended periods of time, restricting the types of behaviors that could be observed. Researchers are now able to address new questions to gain additional mechanistic insights in complex behavior such as social behavior, sleep or spatial navigation. https://www.nature.com/articles/s4159... https://www.caesar.de/en/ https://sfb1089.de/ https://www.mpl.mpg.de/ / caesarbonn / forschungszentrum.caesar / caesar_bonn © caesar Production: Julia Fischer