Looking at the Human Brain in Detail

Exploring the architecture of neuronal circuits is an essential step toward mechanistically understanding how they operate. And since all species present specific adaptations to their own habitats resulting from the selective pressures they are exposed to, exploring the architecture of human neuronal circuits is essential to ensure an efficient transference of knowledge between routine connectomics studies performed in model organisms and human neuroscience ( 1 Loomba S. Straehle J. Gangadharan V. Heike N. Khalifa A. Motta A. et al. Connectomic comparison of mouse and human cortex. Science. 2022; 377eabo0924 Crossref PubMed Scopus (20) Google Scholar , 2 Karlupia N. Schalek R.L. Wu Y. Meirovitch Y. Wei D. Charney A.W. et al. Immersion fixation and staining of multicubic millimeter volumes for electron microscopy–based connectomics of human brain biopsies. Biol Psychiatry. 2023; 94: 352-360 Google Scholar ). In the current issue of Biological Psychiatry, Karlupia et al. ( 2 Karlupia N. Schalek R.L. Wu Y. Meirovitch Y. Wei D. Charney A.W. et al. Immersion fixation and staining of multicubic millimeter volumes for electron microscopy–based connectomics of human brain biopsies. Biol Psychiatry. 2023; 94: 352-360 Google Scholar ) report a new sample preparation protocol that allows staining of electron microscopy (EM) human brain biopsies spanning up to 2 mm in their smallest dimension, thereby paving the way for reliably obtaining connectomes of human neuronal circuits. Simplifying and enhancing the robustness of these protocols will play a critical role in understanding the key signatures of neuronal circuits in health and disease. SEE CORRESPONDING ARTICLE ON PAGE 352 SEE CORRESPONDING ARTICLE ON PAGE 352 Immersion Fixation and Staining of Multicubic Millimeter Volumes for Electron Microscopy–Based Connectomics of Human Brain BiopsiesBiological PsychiatryVol. 94Issue 4PreviewConnectomics allows mapping of cells and their circuits at the nanometer scale in volumes of approximately 1 mm3. Given that the human cerebral cortex can be 3 mm in thickness, larger volumes are required. Larger-volume circuit reconstructions of human brain are limited by 1) the availability of fresh biopsies; 2) the need for excellent preservation of ultrastructure, including extracellular space; and 3) the requirement of uniform staining throughout the sample, among other technical challenges. Full-Text PDF