The central project Z01 consists of two main pillars: The first concerns genetically encoded tools and transgenic mouse lines that allow for the interrogation of engrams and neuronal ensembles with cellular and even synaptic resolution. The second pillar of Z01 is based on the mapping of brain-wide neuronal networks using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Brain function and cognitive performance is the result of a complex interaction between individual brain areas, that make up global neuronal networks (macroscale). These interactions in turn determined by a finely tuned neuronal connectivity at the cellular and synaptic level between brain regions (micro- and mesoscales). Therefore, the aim of project Z01 is to provide state-of-the-art methods for the interrogation of brain circuits at the micro-, meso- and macroscales, which enables CRC members to answer pressing questions like how local neuronal network activity influences global neural networks.
Prof. Dr. med. Frank Angenstein
Since 2012 I am head of the research group “Functional Neuroimaging” at the German Center for Neurodegenerative Diseases (DZNE) in Magdeburg. My work focuses on the search for the neurophysiological basis of fMRI imaging and how different modulatory transmitter systems influence the interaction of the hippocampus with individual cortical and subcortical brain structures under normal and pathological conditions. To address this, individual brain structures are selectively activated by electrical, optogenetic, or chemogenetic stimulation, and the resulting neuronal responses are simultaneously measured both directly by in vivo electrophysiological recordings in the hippocampus and indirectly in the whole brain by fMRI measurements.
Dr. Michael R. Kreutz
Michael R. Kreutz is head of the Neuroplasticity research group at the Leibniz Institute for Neurobiology and he has a second affiliation at the Center for Molecular Neurobiology (ZMNH) in Hamburg where he is heading the Leibniz Group ‘Dendritic Organelles and Synaptic Function’. His research interest is in synapse biology. His work is concerned with fundamental questions on how synapses communicate with the nucleus, how gene activity-dependent gene expression feeds back to synaptic function and how this is related to the formation of a cellular engram and last but not least how the nanoscale organization of the synapse determines functional properties in the context of learning and memory.
Prof. Dr. Oliver Stork
Prof. Dr. Oliver Stork is head of the Department of Genetics & Molecular Neurobiology at the Institute of Biology at the Otto von Guericke University Magdeburg. His research is devoted to understanding molecular and cellular mechanisms underlying the formation and specification of emotional memories. His special focus is on the analysis of local circuit processes in the context of the formation of engram cell assemblies in the hippocampus. He will contribute his expertise in the establishment and integrative analysis of rodent models for behavioral and memory research to the CRC.
In addition to the SFB1436, Prof. Stork is a member of the Magdeburg Collaborative Research Center SFB854 and the German Center for Mental Health in Magdeburg, and serves as a spokesperson for various neuroscientific graduate schools, including the IRTG1436 (this program), the CBBS graduate program and the GRK2413 (deputy spokesperson).
Dr. Cornelia Hesse
In recent years, the focus of my research was and still is the investigation and visualisation of neuronal network activity in the brain of rodents using electrophysiology, functional magnetic resonance imaging (fMRI, 4.7T / 9.4T animal MRI-scanner) and cyclic voltammetry. I was particularly interested how the release of neuromodulators (such as dopamine, noradrenaline, serotonin, adenosine) effect active neuronal networks.
Dr. Guilherme Gomes
I am a Brazilian neuroscientist member of the Research Group Neuroplasticity (LIN). I am interested on the molecular players that give rise to complex behaviors., and over the past 10 years I have been focusing on how NMDAR signaling controls the expression of plasticity-related genes, both in health and disease. As a member of the CRC1436 I am part of project A02, A04 and Z01, and my goal is to provide state-of-the-art methods for engram detection and manipulation to the CRC community
How is the activity of local neuronal networks visualized?
Z01 offers to CRC members a broad variety of genetically encoded tools that can trace and label activated neuronal ensembles, like CaMPARI 2, RAM and Dual e-GRASP).
Some of these methods also allow the use of opto and chemo-genetic tools, which ultimately gives the researchers control over behavior.
How can global neural networks be imaged?
When neuronal activity changes in a particular region, the blood supply to that region also changes. This mechanism, also known as neuro-vascular coupling, can be measured non-invasively with functional magnetic resonance imaging (fMRI). Thus, changes in individual hemodynamic parameters, such as blood flow/volume or blood oxygen saturation, are measured with a high spatial resolution (≤ 400 µm) in the entire brain of the studied animals (mouse, gerbil, or rat). As soon as in different regions the hemodynamic parameters change (correlate) in a similar way within a certain time frame, it is very likely that the neuronal activities present there are also similar, i.e. that these neuronal populations interact.
How to study the influence of local neural network activity on global neural networks?
There are a couple of molecular techniques which can manipulate the activity of specific neurons. Using these molecular techniques, such as the expression of DREADDs (Designer Receptor Exclusively Activated by Designer Drugs) or opsins in specific neurons, the activity in a corresponding local neuronal network can now be specifically altered, e.g. by giving an activator to the DREADDs or stimulating the opsins by laser light. If such a manipulation of a local neuronal network occurs during an fMRI measurement, possible changes of global neuronal networks also become measurable. I.e., comparison of fMRI activation patterns before and during stimulation of DREADDs or opsins shows which interactions between individual brain structures are regulated by the modulated local network.
The goals of our project
In the individual subprojects of the CRC, different cellular mechanisms are investigated that can serve as a neural resource for cognitive flexibility and enable the potential transfer of this performance from one task to another. What all these approaches have in common is that they are mediated by a modification of local network properties, which in turn, in order to become behaviorally relevant, also require changes in global network properties. Therefore, in this central project, we offer methods to identify engram cells and their neuronal ensembles, as well as methods to measure local and global neuronal networks activity. Z01 works as a platform where participating labs can profit from the established tools and from the accumulating expertise of all users.
Look into the future
Central Project Z01 will continue to keep the CRC at the cutting edge of technology to map neural network activity in the context of neuronal resources at the micro-, meso-, and macroscopic levels. In addition, molecular biology techniques will be used to identify, in particular, neuronal networks responsible for engram formation. Targeted activation and thus more detailed characterization of these networks should provide a better understanding on the mechanisms of neural resource for cognitive flexibility.
Publications of the project Z01
Integration of nuclear Ca2+ transients and subnuclear protein shuttling provides a novel mechanism for the regulation of CREB-dependent gene expression
Karpova A, Samer S, Turacak R, Yuanxiang P, Kreutz MR. Cell Mol Life Sci (2023)
Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer’s disease
K. M Grochowska, G. M Gomes, R. Raman, R. Kaushik, L. Sosulina, H. Kaneko, A. M Oelschlegel, P. Yuanxiang, I. Reyes-Resina, G. Bayraktar, S. Samer, C. Spilker, M. S Woo, M. Morawski, J. Goldschmidt, M. A Friese, S. Rossner, G. Navarro, S….
Katarzyna M Grochowska, Maria Andres-Alonso, Anna Karpova, Michael R Kreutz EMBO J (2022)
Brief neuronal afterdischarges in the rat hippocampus lead to transient changes in oscillatory activity and to a very long-lasting decline in BOLD signals without inducing a hypoxic state
Alberto Arboit, Shih-Pi Ku, Karla Krautwald, Frank Angenstein Neuroimage (2021)
Multiomics of synaptic junctions reveals altered lipid metabolism and signaling following environmental enrichment
Maximilian Borgmeyer, Cristina Coman, Canan Has, Hans-Frieder Schött, Tingting Li, Philipp Westhoff, Yam F H Cheung, Nils Hoffmann, PingAn Yuanxiang, Thomas Behnisch, Guilherme M Gomes, Mael Dumenieu, Michaela Schweizer, Michaela Chocholoušková, Michal Holčapek, Marina Mikhaylova, Michael R Kreutz, Robert Ahrends Cell Rep (2021)
The cholinergic system modulates negative BOLD responses in the prefrontal cortex once electrical perforant pathway stimulation triggers neuronal afterdischarges in the hippocampus
Alberto Arboit, Karla Krautwald,, Frank Angenstein J Cereb Blood Flow Metab (2021)