Thesis defense Florian Drawitsch (Donders series 483)

14 December 2020

Promotor: prof. dr. Helmstaedter (MPI Brain Research Frankfurt, Radboud),

Correlative three-dimensional light- and electron microscopy for long-range connectomics

Modern neuroscience has succeeded at characterizing the brain at various descriptive levels. However, (micro-) connectomes resolving the brain's circuitry densely at single synapse resolution still are relatively scarce. The acquisition of such connectomic data generally requires three-dimensional electron microscopy (3D EM), which currently is restricted to relatively small imaging volumes of a few hundred micrometer edge length.  Unfortunately, these technological limitations hinder the connectomic analysis of larger circuits as for example most cortical long-range connectivity.  In order to study how long-range inputs are integrated into local connectomes, a method  allowing to identify the origin of non-local axonal inputs within confined EM volumes would be required. In this work, a novel volumetric light- and electron microscopic correlation method was developed allowing to directly identify the origin of long-range axons in connectomic 3D EM data while only making use of conventional, multi-color fluorescent markers. In addition, the developed method was applied to the sensorimotor system and allowed the connectomic analysis of how primary motor (M1) and secondary somatosensory (S2) cortex long-range inputs are integrated into the local wiring of primary somatosensory (S1) barrel cortex.