Yearbook Articles

Our brain is a complex network of nerve cells that communicate with each other through synapses. We are investigating which proteins are used at these synapses and how different nerve cells and synapses differ from each other. Our findings help us to understand the molecular basis of communication in our brain. This communication is essential for all our brain functions and can be disrupted, for example, in neurodegenerative diseases or in old age.

The brain must create an internal model, a so-called ‘cognitive map’, of its environment in order to successfully navigate to a desired destination. Another purpose of this map is to be able to assess the consequences of a decision in a hypothetical environment that we have not yet experienced in the real world. This may be the basis for our creativity and imagination. It is the goal of our research to understand the neural circuits that underlie our inner thought processes.

Our visual ability to separate objects from background depends greatly on detecting local discontinuities of motion, color, contrast or texture. Computing the characteristics of a texture is surprisingly difficult, as confirmed by the hundreds of thousands of trials that neural networks require to “learn” them. Yet our brains segment and differentiate textures without apparent effort. Our research aims to understand how this is done, using cephalopods’s unique ability to camouflage.

The mammalian brain, with its immense number of neurons and extreme density of communication, is the most complex network we know. Methods for partial and sparse analysis of these networks exist for more than a hundred years. However, obtaining locally complete wiring maps of neuronal networks in the mammalian brain only became possible a few years ago. Our research team has now succeeded in mapping brain tissue from the mammalian brain and analyzing it for traces of previous learning processes.

Although learning and memory are tasks performed by our brain on multiple interconnected levels, we can trace them down to chemical reactions leaving molecular footprints. By visualizing these tiny footprints, we aim to build a molecular model of learning. One important factor seems to be the local production of new proteins near the site of information transfer between nerve cells. We have decoded a logistics principle connecting local protein assembly to increase or decrease of information transfer and clarified questions of energy supply for this process.

The neural networks in the brain are able to perform calculations such as normalization, information storage and rhythm generation. To date, various mathematical models have been established to imitate these individual calculations. We have used the stabilized supralinear network (SSN) as a basic model and found that it can perform several calculations simultaneously. This indicates the possibility of formulating a unified theory of cortical function.

The Neocortex represents the largest and most powerful area of the human brain. Having expanded and differentiated the most during mammalian evolution, it mediates many capacities that distinguish humans from their closest relatives. It also plays a central role in many psychiatric disorders. In 2018 our research group has discovered fundamentally new mechanisms that enable neocortex to rapidly and flexibly adjust information processing to the behavioral requirements of the animal.

Neurons communicate by short electric pulses, the so-called action potentials or spikes. In order to fully understand cognitive functions, knowledge about how spikes encode information is necessary. The research group found that pairwise spike correlations and their linear components shape the coding of information. Linear response functions are one of the most versatile concepts and have been used to understand many neuroscientific topics, though their validity regime is not unlimited.

Recent technological advancement has opened up a new era of neuroscience research to acquire large-scale datasets from the brain, and to model and interpret them by novel analytical techniques and algorithms. Here, computational and mathematical approaches are used to understand how neural activity shapes circuit organization and dynamics. The focus lies on neural circuits that enable animals to navigate to a desired location in space.

 

The Laurent lab at the MPI for Brain Research works on deciphering rules of brain computation using simpler systems and model organisms for experimentation. Much of their interest is focused on cortical computation. The only non-mammalian animals with a layered cortex are the non-avian reptiles, and their cortex is much simpler as compared to mammals. Using turtles and lizards, the group of Gilles Laurent has undertaken a study of visual cortex, of cortical dynamics – travelling waves and oscillations – and of sleep.

The brain’s complex neuronal communication network, its connectome, has to be considered a crucial basis for the brain’s impressive performance. Only in recent years, the partial mapping of connectomes has become possible in mammalian brains: MPG-researchers W. Denk and M. Helmstaedter succeeded in mapping the local connectome of mouse retina. The newly established department of connectomics will now focus on connectomic mapping of the cerebral cortex to understand how sensory experience is combined with novel sensory input for the detection and classification of objects in the environment.

The brain is the most complex system we know. At the MPI for Brain Research two groups were appointed in 2013 that use complementary approaches to address the fundamental functions of neuronal circuits: Tatjana Tchumatchenko’s group uses theoretical approaches to understand information encoding in neuronal circuits. The Laboratory of Johannes Letzkus takes the experimental approach and employs 2-photon microscopy and optogenetic methods to understand which activity patterns occur in neocortical circuits during behavior, and how these activity patterns in turn guide the animal’s behavior.

The change of single communication sites between nerve cells, independent of neighboring sites, is believed to be a cellular basis of learning and memory. An elegant explanation how neurons accomplish this arose from the detection that specific proteins might be synthesized close to contact points. With a combination of sensitive methods MPIH investigators now showed that the diversity of protein building plans in neuronal processes is much higher than anticipated – a drastic change in the picture of the neuronal world.

Neuroblastoma (NB) is a childhood tumor that arises from the sympathoadrenal lineage. The mechanisms that direct sympathetic neuron generation are fundamentally different from the control of neurogenesis in other parts of the nervous system and involve the transcription factor Phox2b and the tyrosine kinase receptor Alk. Mutations in Phox2b and Alk predispose to NB in familiar forms of this disease. The expression of mutant Phox2b and Alk in embryonic sympathetic ganglion cells identified signaling pathways that result in aberrant growth and may contribute to NB predisposition.

Which factors determine whether a stimulus is consciously perceived or unconsciously processed? Here it is investigated how previous knowledge affects perception and its underlying neuronal processes. Furthermore, it is investigated whether conscious perception can be learned. The results show that conscious perception is not solely due to the amount of information that a stimulus carries. Rather, conscious perception is the result of a plastic, integrative process during which current information interacts with previously acquired knowledge.

The properties of the retinal photoreceptors determine the information that the visual system receives for further processing. All mammals have rod photoreceptors for low-light and night vision, and cone photoreceptors for daylight and colour vision. However, this basic blueprint is rather flexible and shows species-specific adaptations to different visual needs, e. g. differences in colour vision, ultraviolet vision in some species, and colour blindness in others. The rod nuclei of nocturnal mammals act as light-collecting lenses for improved light transmission.

Glycine, the simplest of all amino acids, inhibits postsynaptic neurons via strychnine-sensitive glycine receptors and, together with glutamate, enhances neuronal excitation by the activation of excitatory N-methyl-D-aspartate (NMDA) receptors. Studies at the MPI for Brain Research indicate that a distinct NMDA receptor subtype is activated by glycine alone, and thus functions as an “excitatory glycine receptor”. Recent results establish a central role of glycine in the regulation of neuronal excitability.

Glycine and GABA are the two principal inhibitory neurotransmitters in the mammalian central nervous system. Dysfunctions of inhibitory neurotransmission are major causes of neurological diseases like epilepsy or a predominantly spinal form of neuronal hyperexcitability, hyperekplexia. Here, the analysis of genetically modified mice revealed two novel disease genes associated with malfunctioning of inhibitory synapses, the collybistin and the glycine transporter 2 genes. Genetic screening of human patients established mutations in both genes as causal for human disease.

Neurons in primary visual cortex have been thought of as spatially restricted analyzers of the visual field. However, a single neuron’s response is also critically influenced by the visual context outside its receptive field. This report deals with investigations how contextual stimuli get integrated into the activity patterns of the visual cortex and which neuronal structures convey the subthreshold activity crucial for that integration.

Neural synchrony represents a possible mechanism to coordinate distributed neural activity patterns in cortical networks. Evidence is emerging that besides a role for cognitive processes, neural synchrony may function as an important pathophysiological and developmental mechanism in neuropsychiatric disorders, such as schizophrenia.

The retina covers the inside of the eye and, comparable to the film in a photographic camera, represents the light sensitive layer. During embryonic development the retina forms as a protrusion of the future brain and is, therefore, part of the central nervous system. Because of its well defined function, its regular structure and its easy accessibility, the retina serves as a model to study brain function. This report describes the contacts (synapses) between neurons of the retina where the inhibitory neurotransmitter glycine is released.

Nervous system development depends on mechanisms that control the generation of different neuronal subtypes. In the peripheral nervous system, signals from innervated targets elicit the specialization to different functional neuronal subtypes. The target-dependent cholinergic differentiation of sympathetic neurons is mediated in vivo by members of the gp130-cytokine family.

In the cerebral cortex information processing strongly relies on the connectivity between different areas. So far, investigations have concentrated on the role of feed-forward connections linking lower areas to higher order centers. However, there is also a dense network of feed-back connections which transmit signals back to the primary sensory areas. We have investigated the role of these connections using optical and electrophysiological recording techniques in combination with reversible deactivation methods and showed that feed-back connections exert a strong influence over the neuronal processes in early sensory areas. Moreover, we investigated how use-dependent cortical plasticity is related to different states of cortical processing and found that only in states of high frequency oscillatory activity, which are related to wakefulness and attention, an enhancement of the representations of repetitively experienced stimuli can be induced.

The cerebral cortex of mammals consists of two main types of nerve cells: excitatory projection neurons and inhibitory interneurons. The excitatory or inhibitory action is mainly determined by the released transmitter glutamate or γ-amino-butyric acid (GABA). Transmitter release takes place at synapses, the communication sites between nerve cells. The balanced interplay of excitation and inhibition allows for the computational power of the cerebral cortex. A central element of neuronal signal processing is the regulation of transmission strength at synapses. The independent research group “Synaptic regulation and function” studies regulatory mechanisms at glutamatergic synapses with two focal points: the role of electrical signaling at presynaptic nerve endings for transmitter release and long-term plasticity of glutamatergic excitation of inhibitory interneurons. These questions are addressed by use of the patch-clamp technique in brain slices of rodents.

The proper functioning of the nervous system requires a precise interplay of excitatory and inhibitory nerve impulses. Our department investigates the molecular mechanisms of synaptic inhibition in the central nervous system. A particular focus are studies on the function of membrane proteins which mediate or regulate inhibition by the amino acid glycine. By generating mouse mutants for specific subtypes of glycine transporters and glycine receptors, important functions of these proteins in the inhibition of motor and pain pathways could be identified. Our results are important for the development of new neuroactive drugs.