We examined the distribution of pre-synaptic contacts in axons of mouse neurons and constructed whole-brain single-cell neuronal networks using an extensive dataset of 1,891 fully reconstructed neurons. We found that bouton locations were not homogeneous throughout the axon and among brain regions. As our algorithm was able to generate whole-brain single-cell connectivity matrices from full morphology reconstruction datasets, we further found that non-homogeneous bouton locations have a significant impact on network wiring, including degree distribution, triad census, and community structure. By perturbing neuronal morphology, we further explored the link between anatomical details and network topology. In our in silico exploration, we found that dendritic and axonal tree span would have the greatest impact on network wiring, followed by synaptic contact deletion. Our results suggest that neuroanatomical details must be carefully addressed in studies of whole-brain networks at the single-cell level.
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http://dx.doi.org/10.1016/j.celrep.2024.113871 | DOI Listing |
Transl Psychiatry
January 2025
Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these differences. We performed the largest study of sex differences in brain volumes (N = 33,208) by examining sex differences both in the raw brain volumes and after controlling the whole brain volumes.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya, China.
Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by damage to cortical circuits. However, the mechanisms underlying AD-associated changes in long-range circuits remain poorly understood.
Methods: In this study, we used viral tracing and fluorescence micro-optical sectioning tomography (fMOST) imaging to investigate whole-brain changes in the input circuit of the frontal cortex of 5×FAD mice.
Nat Commun
January 2025
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability.
View Article and Find Full Text PDFNat Neurosci
January 2025
Neuroscience Graduate Program, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Development of the mammalian brain requires precise molecular changes across diverse cell lineages. While single-cell RNA abundances in the developing brain have been characterized by single-cell RNA sequencing (scRNA-seq), single-cell protein abundances have not been characterized. To address this gap, we performed mass cytometry on the whole brain at embryonic day (E)11.
View Article and Find Full Text PDFElife
November 2024
Division of Biology and Biological Engineering, Tianqiao and Chrissy Chen Institute for Neuroscience, California Institute of Technology, Pasadena, United States.
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