Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Sahil Loomba (Donders series 587)

7 February 2023

Promotor: prof. dr. M. N. Helmstaedter
C0-promotor: dr. Y. Hua (Shanghai Jiao Tong University School of Medicine, China)

Connectomic comparison of the human and non-human primate cortex to mouse

The questions of how we sense the world and what gives rise to complex brain functions, cognition and behavior have occupied the research in neuroscience for decades. The complexity of cortical organization in the human brain is remarkable. It has encouraged studies in simple model systems such as rodents, as these seemed to be more promising. The recent advances in imaging and genomic technologies have enabled precise mapping of the structural and functional connectivity and their correlation to animal behavior. This has rapidly transformed our understanding of the neurobiological underpinnings of the mechanisms such as sensory perception. However, these remain largely limited to the model systems under consideration. Therefore, it is important to apply similar techniques to the human and non-human primate brains to discover cross-systems generalities. Comparative studies are crucial for understanding the similarities and differences in underlying cortical circuits and evolutionary-driven principles of cortical organization, learning and computation. In this chapter, an overview of connectomic methods at difference spatial scales and resolutions is provided along with their advantages and limitations. Electron microscopy (EM)-based techniques enable complete and unbiased mapping of synaptic connectivity and can thereby reveal local synaptic organization principles of cortical circuits. Recent advances in EM methods are discussed in detail. Lastly, a summary of volumetric EM-based neuronal reconstructions from mouse, macaque and human brain tissue is provided. This comprises the differences in neuropil composition, the synaptic input properties of pyramidal cells and interneurons and the degree of change in cell-type-to-cell-type specific connectivity across species.