Z01
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.
Principal Investigators
Prof. Dr. med. Frank Angenstein
Dr. Michael R. Kreutz
Prof. Dr. Oliver Stork
Co-Workers
Dr. Cornelia Hesse
Dr. Guilherme Gomes
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.