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Human cortex development is shaped by molecular and cellular brain systems.

ABSTRACT: Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cerebral cortex development unfolds along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of variance associated with regional cortical thickness trajectories. Adult cortical change patterns are best explained by cholinergic and glutamatergic neurotransmission. These relationships are supported by developmental gene expression trajectories and translate to longitudinal data from over 8,000 adolescents, explaining up to 59% of developmental change at population- and 18% at single-subject level. Integrating multilevel brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand typical and atypical brain development in living humans.

SUBMITTER: Lotter LD

PROVIDER: S-EPMC10187287 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Regional patterns of human cortex development correlate with underlying neurobiology.

Lotter Leon D LD Saberi Amin A Hansen Justine Y JY Misic Bratislav B Paquola Casey C Barker Gareth J GJ Bokde Arun L W ALW Desrivières Sylvane S Flor Herta H Grigis Antoine A Garavan Hugh H Gowland Penny P Heinz Andreas A Brühl Rüdiger R Martinot Jean-Luc JL Paillère Marie-Laure ML Artiges Eric E Orfanos Dimitri Papadopoulos DP Paus Tomáš T Poustka Luise L Hohmann Sarah S Fröhner Juliane H JH Smolka Michael N MN Smolka Michael N MN Vaidya Nilakshi N Walter Henrik H Whelan Robert R Schumann Gunter G Nees Frauke F Banaschewski Tobias T Eickhoff Simon B SB Dukart Juergen J

bioRxiv : the preprint server for biology 20240810

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distrib ...[more]

PMID: 37205539

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Project description:Retrograde neurotrophin (NT) transport is a specialized form of signal transduction used to conduct information from axons to the cell bodies of central and peripheral nervous system neurons. It is activated upon NT-Trk receptor binding, NT-Trk internalization into signaling endosomes, and their motion along the axon toward the cell body. Brain-derived neurotrophic factor (BDNF) is an abundant NT that modulates key brain and spinal cord functions, and defects in BDNF trafficking are associated with neuronal death, neurodegenerative diseases and in nerve injury. Decades of study have yielded impressive progress in elucidating NT retrograde transport; however, much information remains unclear. For example, while it is known that NT function is dependent on tight control of NT-receptor intracellular trafficking, data describing the precise spatiotemporal molecular dynamics of their axonal to somatic transport are lacking. In past work, we showed the use of discrete, photo-bleaching-resistant quantum dot (QD)-BNDF probes to activate and track BDNF-TrkB receptor internalization; this revealed a rich diversity of molecular motions that intracellular BDNF signaling endosomes undergo within the soma of nodose ganglia sensory neurons. Here, we used combined techniques of discrete QD-BDNF tracking with compartmented microfluidic chambers to characterize retrograde BDNF-TrkB transport over long-ranging distances of primary dorsal root ganglion sensory neuronal axons. Our new findings show that axonal retrograde motion is comprised of heterogeneous mixtures of diffusive behaviors, pauses, and variations in net molecular-motor-dependent transport speeds. Notably, specific molecular dynamic features such as NT speed were dependent on spatial context that could be categorized in distance from distal axons and proximity to the soma and were not entirely dictated by active motor transport speed. The important implication is recognition that NT-receptor retrograde transport is comprised of molecular dynamics, which change over the course of long-range trafficking to shape overall transport and possibly signaling.

Dataset Information

Human cortex development is shaped by molecular and cellular brain systems.

Publications

Regional patterns of human cortex development correlate with underlying neurobiology.

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