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Scientists from the Max Planck Institute of Neurobiology in Martinsried have developed a method that allows them to identify nerve cells involved in a specific motor command. For the first time, it is now possible to evoke behaviour of a small fish by artificially activating just a handful of neurons. Understanding the core components of a neural circuit is a key step for deciphering the complex code underlying even elementary brain functions.

Recent years have seen much progress in understanding of the brain’s structure and function. Advances in microscopy and functional imaging enable researchers to monitor the activity of neuronal populations, while an animal perceives sensory stimuli or generates specific behaviours. However, these studies often cannot distinguish cause from consequence of the observed changes in activity. Using the method of optogenetics, scientists can find out which neurons are essential for the chain of events that ultimately lead to behaviour, and which neurons may serve other tasks or are merely by-standers. A particular challenge for this field of research is the staggering degree of "interconnectedness" of neuronal networks. Activating even a single neuron may send ripples through a large part of the nervous system. The new study from Herwig Baier and his team at the Max Planck Institute of Neurobiology has removed both obstacles in one sweep: it is now possible to pinpoint cause and effect to the cellular components of neural circuitry while simultaneously watching how activity propagates through the entire brain network and evokes behaviour.

The Martinsried scientists developed a workflow allowing the 3D photo-stimulation of multiple targeted neurons while, at the same time, imaging network activity in the brain of a zebrafish larva. “The zebrafish with its small, translucent brain is ideal for our new method”, explains Marco dal Maschio, one of the two lead authors of the publication describing the technique.

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Folds in the human brain enlarge the surface of this important processing organ and in this way create more space for higher functions including thought and action. However, certain species of mammals exist whose brains have smooth surfaces, for example mice. Scientists from the Max Planck Institute of Neurobiology in Martinsried have discovered a previously unknown mechanism for brain folding. Young neurons, which migrate to the cortex during the development of a smooth-surfaced brain, have so-called FLRT receptors on their cell surface. These ensure a certain degree of adhesion between the cells and regular migratory behaviour which favours the formation of a smooth brain surface. Compared to the mouse brain, in the human brain FLRTs are much less abundant. If the expression of FLRTs in the mouse brain is reduced experimentally, folds similar to those found in the human brain form. These findings provide new insights into the evolution of smooth and folded mammalian brains.

The human brain has many grooves and furrows which enlarge the brain surface considerably compared to that of a smooth brain. Homo sapiens is not the only species to form folds in the brain, however. It is likely that the ancestral mammal, which lived around 200 million years ago, also had a folded brain. Over the course of evolution, various mammalian species lost their brain folds again. Hence mice and rats, for example, have brains with smooth surfaces.

“The evolutionary success of these and other animal species with smooth brains shows that having a brain without folds is not necessarily disadvantageous and works well for these species,” explains Rüdiger Klein, a Director at the Max Planck Institute of Neurobiology. “We were interested in how brain folds actually arise.”

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In order to successfully survive in a changing environment, animals must be able to combine sensory inputs with information about their own movement. Complex motor behaviors, like walking or riding a bike, would be difficult to perform without feedback signals such as the sense of the feet touching the ground or the perception of movement with respect to the world. Scientists from the Max Planck Institute of Neurobiology in Martinsried use zebrafish as a simple vertebrate model to study how different kinds of sensory and motor information map onto the cerebellum. Their recent study shows that scientists need to rethink about how this large and important part of the brain of all vertebrates, including humans, works.

In a recent study published in the journal Current Biology, Laura Knogler and her colleagues from the Portugues group at the Max Planck Institute of Neurobiology used small translucent larval zebrafish to record cerebellar activity. For the first time, scientists were thus able to record from all the granule cells in the cerebellum of an awake, behaving vertebrate. As Laura explained: “This is possible because the brains of these fish are small, less than 1 mm cubed, and because we can express fluorescent proteins in their brains that light up when neurons are active.” When asked to summarize the main findings, Laura continues: “We were surprised to see that a large fraction of the cerebellar granule cells, nearly 50%, were active when we presented simple sensory stimuli such as light flashes or moving scenes. Some neurons were only active when the fish swam.”

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Schopf FH, Biebl MM, Buchner J.
Nat Rev Mol Cell Biol, 2017, [Epub ahead of print].

The HSP90 chaperone machinery.

The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of proteostasis under both physiological and stress conditions in eukaryotic cells. As HSP90 has several hundred protein substrates (or 'clients'), it is involved in many cellular processes beyond protein folding, which include DNA repair, development, the immune response and neurodegenerative disease. A large number of co-chaperones interact with HSP90 and regulate the ATPase-associated conformational changes of the HSP90 dimer that occur during the processing of clients. Recent progress has allowed the interactions of clients with HSP90 and its co-chaperones to be defined. Owing to the importance of HSP90 in the regulation of many cellular proteins, it has become a promising drug target for the treatment of several diseases, which include cancer and diseases associated with protein misfolding.