Structural Neurobiology

Molecular, Ultrastructural and Functional Profiles of Neuronal Circuits in the Healthy and Diseased Brain

Our research aims to reveal the molecular, ultrastructural and functional profiles of neuronal circuits that underlie neuronal computations and cognition in the healthy and diseased brain.  We address these fundamental questions using a dynamical proteo-connectomics approach that combines behavioral experiments, in vivo multiphoton calcium imaging, ultra-highplex proteomics, X-ray and volume electron microscopy with dense neuronal circuit reconstruction, computational modeling and network analysis. We are developing novel electron and X-ray microscopy techniques for dense, multiscale imaging of neuronal circuits from individual synapses in local circuits to single cell resolution projection patterns.

Our research is generously supported by

  • a SERI-funded ERC Starting Grant
  • the Swiss National Science Foundation
  • the NIH BRAIN CONNECTS program
  • the SNI PhD School
  • the PSI Fellow Program
     
Dynamical Connectomics workflow
Mice are being trained to perform different behavioral tasks in virtual reality setting. While the mice are performing the tasks, in vivo multiphoton calcium imaging is used to record the activity of hundreds of neurons with single cell resolution. Subsequently, the same brain area is processed for ultrastructural imaging by volume electron microscopy or by X-ray computed nanotomography. Finally, deep learning-based automated image processing is used to reconstruct all neurons, their synaptic connections and ultrastructural organization.

Lab. of Nanoscale Biology
Paul Scherrer Institute PSI
Forschungsstrasse 111
5232 Villigen PSI, Switzerland