The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on "full" human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of "full" human neuron morphologies and present direct evidence that human neurons are not "scaled-up" versions of rodent or macaque neurons, but have unique structural and functional properties.
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http://dx.doi.org/10.1093/cercor/bhv188 | DOI Listing |
J Comp Neurol
January 2025
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu, India.
Direction selectivity is a fundamental feature in the visual system. In the retina, direction selectivity is independently computed by ON and OFF circuits. However, the advantages of extracting directional information from these two independent circuits are unclear.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Pharmacology, School of Health Sciences, Central University of Punjab, Bathinda, 151401, India.
Background: Multiple sclerosis (MS) is a chronic autoimmune condition that damages the myelin sheath of neurons in the central nervous system, resulting in compromised nerve transmission and motor impairment. The astrocytopathy is considered one of the prominent etiological factor in the pathophysiology of demyelination in MS. The expression level of ceramide synthase-2 (CS-2) is yet to be established in the pathophysiology of astrocytopathy although the derailed ceramide biosynthetic pathways is well demonstrated in the pathophysiology of demyelination.
View Article and Find Full Text PDFNat Neurosci
January 2025
Sagol Department of Neuroscience, The Integrated Brain and Behavior Center, University of Haifa, Haifa, Israel.
To protect the body from infections, the brain has evolved the ability to coordinate behavioral and immunological responses. The conditioned immune response (CIR) is a form of Pavlovian conditioning wherein a sensory (for example, taste) stimulus, when paired with an immunomodulatory agent, evokes aversive behavior and an anticipatory immune response after re-experiencing the taste. Although taste and its valence are represented in the anterior insular cortex and immune response in the posterior insula and although the insula is pivotal for CIRs, the precise circuitry underlying CIRs remains unknown.
View Article and Find Full Text PDFNat Methods
January 2025
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Teravoxel-scale, cellular-resolution images of cleared rodent brains acquired with light-sheet fluorescence microscopy have transformed the way we study the brain. Realizing the potential of this technology requires computational pipelines that generalize across experimental protocols and map neuronal activity at the laminar and subpopulation-specific levels, beyond atlas-defined regions. Here, we present artficial intelligence-based cartography of ensembles (ACE), an end-to-end pipeline that employs three-dimensional deep learning segmentation models and advanced cluster-wise statistical algorithms, to enable unbiased mapping of local neuronal activity and connectivity.
View Article and Find Full Text PDFNat Methods
January 2025
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often limited to one or two modalities, offering an incomplete view of cellular identity. Here we present spatial-Mux-seq, a multimodal spatial technology that allows simultaneous profiling of five different modalities: two histone modifications, chromatin accessibility, whole transcriptome and a panel of proteins at tissue scale and cellular level in a spatially resolved manner.
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