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URPP Adaptive Brain Circuits in Development and Learning (AdaBD)

Expanding the Dynamic Range of Light Microscopy-based Analysis of Physiological and Aberrant Neural Circuit Development (EXPAND)

AdaBD made easy

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How can we look into tiny things, such as nerve connections?

In this project, we establish laboratory techniques and microscopy approaches to be able to visualize nerve connections in different model systems. For example, we are using a special preparation tool to expand tissues up to 20 times. We are applying these techniques to investigate the effects on neural circuit formation of gene variants causing neurodevelopmental disorders such as autism.

purkinje cells from the cerebellum
Purkinje cells from the cerebellum (Gonzalo Saiz-Castro, Stoeckli Lab)

Research project

The project EXPAND combines Expansion Microscopy (ExM), a method that expands biological samples up to 20 times, with other super-resolution microscopy approaches to investigate chemical synapses and neural circuits an the nanometer scale. Moreover, neural circuits will be imaged in large samples with increased resolution by combining ExM with mesoscale selective plane illumination microscopy (mesoSPIM). This allows us to bridge the gap between the subsynaptic and the neural circuit level and to elucidate how gene variants causing neurodevelopmental disorders (e.g. FOXP1) affect neural circuit architecture across spatial scales.

We currently analyze the role of FoxP, a gene family associated with autism spectrum disorders, in axon guidance in chicken embryos. In addition, we combine ExM and stumulated emission depletion (STED) super-resolution microscopy to probe homeostatic modulation of synaptic nano-architecture in human iPSC-derived neurons, as well as Drosophila synapses.

This project will provide the URPP with a versatile toolbox and an experimental pipeline that allows the systematic examination of neural circuits at increased resolution, and the characterization of candidate disease genes identified in patients.

Research groups

Principal investigators: Martin Müller, Esther Stoeckli, Anita Rauch

PhD students: Nasrin Bollmohr, Marta Brasili, Lisa Kistler, Hanna Yeliseyeva

Collaborators: Gonzalo Saiz-Castro, Gabriele Siegel, Severino Thomasin

Platforms: mesoSPIM

Publications

Nair AG*, Bollmohr N*, Schökle L, Keim J, Melero JMM, Müller M (2024)
Presynaptic quantal size enhancement counteracts post-tetanic release depression. J Physiol.

Muttathukunnel P, Frei P, Perry S, Dickman D, Müller M (2022) Rapid homeostatic modulation of transsynaptic nanocolumn rings. PNAS 119. 

Underlined: Current and previous AdaBD researchers
*: Equal contribution