Synapses

Support large-scale molecular profiling of neuronal populations and synapses in the Brain Proteome Organization team. Contribute to experimental workflows studying how proteins and their interactions shape synaptic physiology and brain-circuit connectivity.

Binary and analog variation of synapses between cortical pyramidal neurons

n the neurosciences the need for some 'overarching' theory is sometimes expressed, but it is not always obvious what is meant by this. One can perhaps agree that in modern science observation and experimentation is normally complemented by 'theory', i.e. the development of theoretical concepts that help guiding and evaluating experiments and measurements. A deeper discussion of 'brain theory' will require the clarification of some further distictions, in particular: theory vs. model and brain research (and its theory) vs. neuroscience. Other questions are: Does a theory require mathematics? Or

Neurons use a variety of strategies, including local protein synthesis and pre-established protein pools inside dendrites, to maintain the dynamic proteome requirements for appropriate synaptic activity. While certain proteins have local mRNA that allows for on-demand synthesis at the synapse, the vast majority do not. This poses an important question: how can these proteins manage their copy number without boosting the synthesis rate locally? This study looks into the hypothesis that the amount of the protein pool in dendrites corresponds with the presence or lack of dendritic mRNA for local

Neural networks need to continuously adapt their representations to survive in a constantly changing environment. To test behavioral flexibility reversal learning paradigms are often used [1]. This flexible adaptation of entrained representations can be mediated by unlearning and forgetting [2]. One possible factor for passive forgetting could be the spontaneous remodeling of neuronal circuitry [3]. Acknowledging that previous studies have presented conflicting views on the effects of forgetting during reversal learning, we hypothesize two potential scenarios: Hypothesis I ('Reusing'): Reusing

…properties of individual neurons and synapses contribute to neuronal circuit dynamics and behavior. In recent years we have done both computational and experimental studies that demonstrate that the same physiological output can arise from multiple, degenerate solutions, and that individual animals with similar behavior can nonetheless have quite different sets of underlying circuit parameters. Most recently, we have been studying the resilience of individual animals to perturbations such as temperature and high potassium concent

…Also synapses are key elements for healthy brain functioning. The synapses of neurons are highly dynamic, especially during early period of lifetimeand. Their rate increased during embryogenesis but subsequently unnecessary synapses are eliminated through a process called pruning modulated by autophagy. Many studies have shown that autophagy is a

…about the functional state of synapses during brain development. Quantifying dendritic spine shape changes will boost the comprehension of several neuropathies, such as Alzheimer and autism spectrum. Detection of dendritic spines is challenged by optical limitations. We propose a fully automated pipeline to segment and cluster spines to classify them according to th

Brain tissue comprises an extremely complex arrangement of cells that together make up the information- processing network enabling brain function. The connectivity of neurons underlies the unparalleled capabilities of our mind. Thus, mapping brain structure, which underlies brain function, has become a central focus in neuroscience.Electron microscopy provides extremely high resolution and comprehensive visualization of brain structure but requires correlative workflows to access molecular information. Light microscopy holds tremendous potential to analyze the ultrastructure of brain tissue t

…the mouse hippocampus, properties of synapses between pyramidal cells depend on the hemispheric origin of presynaptic inputs. In the CA3-CA1 connection, right-input synapses in stratum radiatum have larger postsynaptic density (PSD) and higher perforation ratio, expressing lower NR2B subunit density, than left-input synapses. The major histocompatibility complex class I (MHCI) and Paired immunoglobulin-like receptor B (PirB) contribute to this asymmetry, suggesting potential trans-synaptic signal

Neurons communicate through the formation of specialised junctions termed synapses, established by formation of extended protein networks. Our aim is to gain insights about the protein environment of the synapse by identification of novel proteins through employment of unbiased quantitative proteomic approaches. Here, we show results from a proteomic analysis of synaptic CAH10 protein complexes, which were affinity isolated from mouse brain. CAH10 was recently described as a pan-neurexin ligand. The interactome of CAH10 consists of presynaptic, secreted and post-synaptic proteins. Among them,

The serine-threonine kinase Ndr2 controls axonal and dendritic growth in vertebrates and invertebrates. Further work from our group has shown that Ndr2 KO mice display deficits in synapse development, and plasticity, that lead to spatial memory impairment. Moreover, the Ndr family of kinases have recently been implicated in the regulation of autophagy, which is essential for memory formation and cognitive function during ageing. Nonetheless, the question of whether Ndr2 is involved in age-related autophagy dysregulation and the cognitive decline associated with it remained. In the current stud

Quantifying the number and strength of synapses, and how these change over time is critical to understanding neuronal activity and plasticity. The dynamics of dendritic spines and the molecular composition of dendrites is strongly dependent on image analysis that can detect the position and quantity of labelled proteins and mRNAs of interest. Usually, light microscopy images are analyzed manually and involves switching between multiple software packages to locate spines, track dendrites, or identify mRNA puncta for each process step. State-of-the-art automated tools, while powerful, can often

Neurons communicate at specialized terminals called synapses, where hundreds of molecules work together in harmony to ensure proper and efficient signal transmission, which is crucial for normal brain functions. Aberrant synaptic signalling is involved in many neurodevelopmental and neurodegenerative diseases such as autism and Parkinson’s disease. This highlights the need to understand the organization and interactions of molecular complexes at the synapse. Cryo-electron tomography (cryo-ET) offers a close-to-native preservation of biological specimen and the unique possibility to capture bot

Memory is the capacity of an organism to acquire, store and recover information based on experience. In the brain, experiences that become memories appear as enduring changes only in a small set of activated neurons, called engrams.While the mechanisms of how such memories are deposited in engrams for short periods of time has received considerable attention over the past decade, the current knowledge of how memories are stored in engram cells in the long run is still scarce. Consequently, this project aims to identify the mechanisms based on which a memory becomes remote by integrating a wide

…view of storage through changes in synapses.

Memories are thought to be stored in synapses between neurons, but these connections in the hippocampus show complete turnover within a fortnight[1]. Dynamics have also been seen at the representational level, as the cells responding to a particular position change across days even when the animal isn’t overtly learning or forgetting[2]. While some researchers consider representational dynamics to be an inevitable consequence of ongoing learning, others suggest that drift may be beneficial. For instance, theoretical work by Kappel et al.,[3] suggests that if initial learning leads the system t

The complex morphology of neurons, with synapses located hundreds of microns from the cell body, necessitates the localization of important cell biological machines, including ribosomes, within dendrites and axons. Local translation of mRNAs is important for the function and plasticity of synapses. Using advanced sequencing and imaging techniques we have updated our understanding of the local transcriptome and identified the local translatome- identifying over 800 transcripts for which local translation is the dominant source of protein. In addition, we have explored the unique mechanisms neur

Connections between nerve cells called synapses are the fundamental units of communication and information processing in the brain. The accurate wiring of neurons through synapses into neural networks or circuits is essential for brain organization. Neuronal networks are sculpted and refined throughout life by constant adjustment of the strength of synaptic communication by neuronal activity, a process known as synaptic plasticity. Deficits in the development or plasticity of synapses underlie various neuropsychiatric disorders, including autism, schizophrenia and intellectual disability. The

In the adult brain, synapses are tightly enwrapped by lattices of extracellular matrix that consist of extremely long-lived molecules. These lattices are deemed to stabilize synapses, restrict the reorganization of their transmission machinery, and prevent them from undergoing structural or morphological changes. At the same time, they are expected to retain some degree of flexibility to permit occasional events of synaptic plasticity. The recent understanding that structural changes to synapses are significantly more frequent than previously assumed (occurring even on a timescale of minutes)

…work has shown that in naive animals, synapses on CRH neurons in the paraventricular nucleus of the hypothalamus are very reluctant to modification. If animals are stressed, however, these synapses become willing to learn. This seminar will focus on mechanisms linking acute stress to metaplastic changes at glutamate synapses, and also show how stress, and these synaptic changes can be transmitted

…and manifests both locally where synapses with similar functional properties are clustered, and globally along the axis from dendrite to soma. Recent experiments reveal species-specific differences in the local and global synaptic organization in mouse, ferret and macaque visual cortex. I will present a computational framework that implements functional and structural plasticity from sp