Archive - Yearbook Articles of the MPI of Neurobiology 
(full texts in German)

Neurodegenerative diseases are devastating disorders for which no cure currently exists. The molecular mechanisms of these diseases are still not well understood. A characteristic feature of neurodegeneration is the accumulation of protein aggregates in the brain. Scientists at the Max Planck Institute of Neurobiology investigate the effects of aggregates on nerve cells, using histological and biochemical methods, behavioral tests and in vivo microscopy. The aim of these studies is to gain a deeper understanding of how diseases develop, in order to develop better treatments in the future.

As soon as we open our eyes and look around, we immediately realize where we are, which objects surround us, and in which direction they are moving. All this information is contained within the images that our e eyes deliver to our brain, but only implicitly: to extract it in an explicit way, our brain has to compute. But how do nerve cells compute? Using motion vision in the fruit fly Drosophila as an example for neural computation, we were able to answer this question in large parts within recent years.
 

The mammalian brain consists of hundreds of cell populations that all carry the same genetic information in the cell nucleus. How do neurons become specified as one differentiated subtype versus another? The ganglionic eminences (GE) are embryonic brain structures that produce many GABAergic cell types which disperse widely throughout the brain. We use single-cell RNA sequencing to profile the transcriptomes of developing neurons, in combination with genetic fate mapping techniques. Our findings shed new light on the molecular diversification of precursor cells.

A glance or a gesture is often enough to assess the intention of a neighbor and adapt one's own behavior to it. In a virtual environment for zebrafish larvae, we have succeeded in animating individual fish to shoal with simulated conspecifics. The results provide insights into the mechanisms of perception of signals that trigger social behaviour.

Directed evolution of proteins in vitro harbors great potential to generate tailor-made tools for applications in neuroscience. Our group has built an imaging-based screening platform that allows high throughput validation of hundred thousands of protein variants expressed in bacteria. We have used the platform to optimize a fluorescent protein that is particularly useful for labeling structures that are located deep within the brain.

The amygdala is part of multiple neuronal circuits which coordinate energy balance, emotions and reward. In this process, distinct neuronal cell types of the amygdala take on different tasks. Recently described "pleasure neurons" of the amygdala associate food consumption with positive emotions. Artificial activation of these neurons increases food intake in mice even when they are not hungry. Malfunctions of this amygdala circuit could result in eating disorders.

Understanding how the brain processes incoming sensory information and generates appropriate behavior is one of the greatest challenges in science. Thanks to their transparent brain and readily modifiable genes, zebrafish (Danio rerio) larvae provide an unparalleled opportunity to tackle this question at the level of individual neurons and neural circuits. Using zebrafish, the Max Planck scientists have discovered a key mechanism that distinguishes between different patterns of visual motion and drives the appropriate behavioral responses.

The cortex of the human brain is folded into an intricate pattern of grooves and furrows, which affords the cortex surface to be large, despite the small cranial space. But not all mammals have such a folded brain surface. By using a genetic manipulation, scientists at the Max-Planck Institute of Neurobiology have induced folds in the normally smooth surface of the mouse brain. The results have given insight into the underlying mechanisms that control brain folding.

The perception and reaction to food odors and tastes can change dependent on internal state and needs. How these perceptual changes are brought about is not well understood. Recent findings have shown that female fruit flies (Drosophila melanogaster) change their perception and behavior after mating to preferring polyamine-rich diets, which they identify with specific odor and taste receptors. The results suggest that physiological needs influence sensory perception and, ultimately, behavior, enhancing reproductive success and survival.

The brain performs its computations based on information from the sensory organs. If this input changes, for instance after an injury, the brain has the ability to adapt. Ideally, after the disturbance has passed, the brain`s processing returns to normal state. Recent studies show that not only the general processing capabilities but also the detailed neural circuits return to their original state. In addition, the work also demonstrates that new neurons can be functionally integrated - even in the adult brain.

A key function of the brain is to integrate incoming sensory information, and to select the optimal behavior in response to these external cues. The underlying computations in the brain are extremely complex and poorly understood. To address this area of research, scientists use the transparent larval zebrafish as model organism. With the aid of powerful microscopes, scientists can monitor the whole brain activity at single cell resolution in the intact, behaving animal. This helps to understand how neuronal circuit dynamics translate sensory processing into behavioral output.

The brain's wiring diagram is a map of information paths, containing the brain's software. The first wiring diagram of an entire brain (published in 1986) came from the roundworm C. elegans with its few hundred neurons. In contrast, the mouse brain has almost 100 million and the human brain about 100 billion neurons. Nevertheless, today it is no longer unthinkable to obtain at least a mouse brain's diagram. The first step on this path is already made: the development of a preparation with sufficient resolution and contrast. Work on methods for cutting, imaging, and analysis is in progress.

The brain’s insular cortex integrates sensory information with emotions and cognitive content. Insular alterations have frequently been described in neurological disorders such as Autism and Schizophrenia. New discoveries show that sensory integration properties of the insular cortex are impaired in mouse models of autism. An imbalance between excitatory and inhibitory synapses underlies this integration deficit. The balance could be permanently reinstated through early drug treatments. The results could potentially lead to the development of novel therapies or early diagnostic markers.

When flies perform their incredible aerobatic maneuvers, they rely, to a large extent, on visual cues. Accordingly, flies dedicate more than 50% of all their nerve cells to process the images coming from their large facet eyes. Thanks to the advent of sophisticated genetic methods available in the fruit fly Drosophila allowing for targeting and manipulating individual nerve cells, recent years have seen much progress in our understanding of the neural circuits involved. The results reveal astonishing parallels to the ones found in the mammalian retina.

The nervous system is characterized by extremely complex cell-cell interactions which primarily happen through chemical synapses. Mapping the structure of these intercellular networks is one of the major challenges in Neuroscience. The new field of Connectomics aims at the dense reconstruction of increasingly comprehensive nerve cell networks. Automated volume electron microscopy techniques are used for image acquisition. A major obstacle, however, is data reconstruction, for which unusual solutions such as mass reconstruction by crowd sourcing and online computer games are currently pursued.

Lately a lot of progress has been made, enhancing our understanding of how information is stored in the brain. It has become clear that changes in the points of connection between neurons – the synapses, play a major role. Technological progress in recent years has made it possible to actually observe such changes in the living brain. These observations clearly demonstrate functional as well as structural changes in the synapses. One remaining challenge is to observe and verify these changes in animals behaving and learning in a natural or at least semi-natural environment.

How are complex processes such as sensory perception, regeneration of nervous tissue or the activation of the immune system during autoimmune disease orchestrated within the living organism? Although these questions appear quite different, fluorescent proteins offer tailor-made tools for these research areas. Scientists enhance their skills in designing and using these indicator proteins – from bacteria to neurons in mice. The design and properties of the proteins can be modified so that they show e.g. biochemical signal cascades or the firing of action potentials in neurons.

Insects use their sense of smell to find food, mating partners or to avoid danger. Carbon dioxide is an important cue for insects. Interestingly, fruitflies reject it strongly, while mosquitoes use it to find human or animal hosts for blood feeding. CO₂ and its detection is a field of active research, because we hope to contribute knowledge to the fight against malaria and other deadly diseases. Certain genes could have played an important role during evolution making mosquitoes attracted and fruitflies repelled by CO₂.

Our movements are controlled by nerve cells located in the spinal cord. Before birth, these cells have to be connected with the correct muscles, some of which are situated far away from the spinal cord, like the muscles of the lower leg. To reach their destination, the processes of nerve cells have to cover large distances, growing through different tissues. How do they find their way in this complex environment? Scientists from the Max Planck Institute of Neurobiology use genetic and cell biological methods to study the molecular signals that help the growing nerves navigate through the body.

How does the mind perceive the world? This is not a trivial question: for many animal species, "seeing" is one of the most important senses. In order to understand such complex processes like the perception of movement, neurobiologists at the Max Planck Institute of Neurobiology study a somewhat simpler yet highly efficient system – the fly brain. The researchers use the latest technologies and thus unravel piece by piece the functions of the network on the level of individual nerve cells.

Synapses are the contact points between nerve cells. The word synapse originates from the Greek words syn (together) and haptein (touch). It is easy to imagine that special molecules exist not only to keep these contacts in place but also for the development of synapses. In the recent years various proteins, also called adhesion molecules, have been identified. SynCAM1, one of these proteins, has now been studied in more detail.

Flies are able to learn to approach or to avoid a certain odor. Hiromu Tanimoto and his Max Planck Research Group at the MPI of Neurobiology in Martinsried aim to understand how the association of odor and behavior is formed in the brain of fruit flies and how these distinct forms of memory are translated into behavior. To this end, the scientists take advantage of genetics, behavior, anatomy, and theoretical approaches.

Multiple sclerosis (MS) is a very complex disease whose causes and underlying mechanisms are still partially unresolved. Quite a number of new insights contributed by the neuroimmunologists of the MPI of Neurobiology help in piecing together this puzzle. The thus generated detailed picture of the MS is essential for the later development of new approaches to the treatment of the disease.

Scientists are beginning to get the gist of what happens in the brain when it learns or forgets something. A whole series of discoveries now shows how and where nerve cells create contacts between each other, or what happens, when the flow of information is disrupted or needs to be reestablished after a period of time. The results provide an intimate view into the fundamental functions of the brain.

An injury of nerve cells in the brain or spinal cord has generally serious consequences, since these cells can not regrow – in contrast to nerve cells e.g. in the arms or legs. For the first time scientists were now able to investigate the processes within an injured nerve cell. The investigations showed that the stabilization of small protein tubes within the cells is crucial for the cells' growth. The results could also lead to novel therapies.

Parkinson disease is characterized by a massive loss of nerve cells in a specific brain region. It was shown that the Ret receptor, which is activated by the neurotrophic factor GDNF, is essential for the survival and regeneration of nerve cells in this brain region. These results advance our understanding of the molecular mechanisms in the aging brain and may facilitate the development of new therapies for Parkinson disease.

The function of the immune system is to defend against intruders such as viruses and bacteria. In case of Multiple Sclerosis, however, the immune system attacks the central nervous system. A newly found mechanism of this disease now reveals how the immune system’s antibodies can attack nerve cells directly. The results could lead to new therapy approaches for some patients.

Neurons in many species have large receptive fields that are selective for specific optic flow-fields. In a recent study the neural mechanisms underlying flow-field selectivity in the so-called H2-cell of the blowfly was investigated. For the first time it was shown that the direct contact between two cells from opposite brain hemispheres is sufficient to explain flow-field selectivity of a neuron utilized by the blowfly for appropriate steering maneuvers.

A hallmark of the brain is its ability to change functional connectivity in response to experience, providing - as it is presumed - the neurobiological basis for memory storage. Two recent studies from the Department of Cellular and Systems Neurobiology report on novel facets of the plasticity of synaptic connections. It was shown that the functional downregulation of synaptic connections, called long-term depression, is associated with the disappearance of tiny structural protrusions, named dendritic spines, which normally allow neurons to form excitatory synapses by attaching their presynaptic partners. By physically disrupting a synaptic connection, the loss of spines may thus could be one way of how a synaptic coupling between neurons becomes weakened in a long-lasting manner. In a second study it was demonstrated that synapses which were potentiated or strengthened at about the same time started to compete for the same set of proteins needed to maintain the elevated state of synaptic coupling: if the available pool of proteins is limited, additional strengthening of a subset of synapses leads to a weakening of previously potentiated synapses.

Multiple sclerosis is an inflammatory disease of the central nervous system (CNS) mediated by autoimmune T- and B-lymphocytes. The role of B cells is largely unknown. A recent study showed that brain resident cells (astrocytes) produce a factor, named BAFF, which promotes the survival of B-lymphocytes. While BAFF is present in the healthy brain, its production is highly elevated in inflammatory brain lesions of MS patients. Thereby the CNS seems to provide a “B cell friendly” environment which promotes the survival of inflammatory cells inside of the CNS of MS patients.

The tasks of the human brain, as well as the animal brain, are fairly complex: On the one hand an uninterrupted stream of sensory input has to be processed, on the other hand at the same time memories have to be stored, sometimes for a lifetime, and retrieved. The generation and storage of new information-codes, as well as the transmission of chemical messengers between neurons occurs at the synapses. But what are the cellular and biochemical mechanisms of learning and memory?

During development of the nervous system each neuron is generating a long process called axon and several short, widely ramified structures called dendrites. Each of those axons is developing a growth cone from which foot- and tentacle-like extensions are protruding (lamellipodia and filopodia). The neurons are thus able to channel through tissue or contact other nerve cells to build a complete nervous system. Other cells that are contacted by a migrating neuron are leading the way, such that they first bind to the respective neuron and reject it shortly after.