Postnatal development and maturation of layer 1 in the lateral prefrontal cortex and its disruption in autism
Trutzer, Iris Margalit
Garcia-Cabezas, Miguel Angel
MetadataShow full item record
Citation (published version)Iris Margalit Trutzer, Miguel Angel Garcia-Cabezas, Basilis Zikopoulos. 2019. "Postnatal development and maturation of layer 1 in the lateral prefrontal cortex and its disruption in autism." ACTA NEUROPATHOLOGICA COMMUNICATIONS, Volume 7, 23 p. https://doi.org/10.1186/s40478-019-0684-8
Autism is a neurodevelopmental connectivity disorder characterized by cortical network disorganization and imbalance in excitation/inhibition. However, little is known about the development of autism pathology and the disruption of laminar-specific excitatory and inhibitory cortical circuits. To begin to address these issues, we examined layer 1 of the lateral prefrontal cortex (LPFC), an area with prolonged development and maturation that is affected in autism. We focused on layer 1 because it contains a distinctive, diverse population of interneurons and glia, receives input from feedback and neuromodulatory pathways, and plays a critical role in the development, maturation, and function of the cortex. We used unbiased quantitative methods at high resolution to study the morphology, neurochemistry, distribution, and density of neurons and myelinated axons in post-mortem brain tissue from children and adults with and without autism. We cross-validated our findings through comparisons with neighboring anterior cingulate cortices and optimally-fixed non-human primate tissue. In neurotypical controls we found an increase in the density of myelinated axons from childhood to adulthood. Neuron density overall declined with age, paralleled by decreased density of inhibitory interneurons labeled by calretinin (CR), calbindin (CB), and parvalbumin (PV). Importantly, we found PV neurons in layer 1 of typically developing children, previously detected only perinatally. In autism there was disorganization of cortical networks within layer 1: children with autism had increased variability in the trajectories and thickness of myelinated axons in layer 1, while adults with autism had a reduction in the relative proportion of thin axons. Neurotypical postnatal changes in layer 1 of LPFC likely underlie refinement of cortical activity during maturation of cortical networks involved in cognition. Our findings suggest that disruption of the maturation of feedback pathways, rather than interneurons in layer 1, has a key role in the development of imbalance between excitation and inhibition in autism.
Rights© The Author(s). 2019. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Showing items related by title, author, creator and subject.
Zikopoulos, Basilis; Barbas, Helen (FRONTIERS MEDIA SA, 2013-09-27)Converging evidence from diverse studies suggests that atypical brain connectivity in autism affects in distinct ways short- and long-range cortical pathways, disrupting neural communication and the balance of excitation ...
Resting state connectivity between medial temporal lobe regions and intrinsic cortical networks predicts performance in a path integration task Izen, Sarah C.; Chrastil, Elizabeth R.; Stern, Chantal E. (FRONTIERS MEDIA SA, 2018-10-16)Humans differ in their individual navigational performance, in part because successful navigation relies on several diverse abilities. One such navigational capability is path integration, the updating of position and ...
Parallel trends in cortical gray and white matter architecture and connections in primates allow fine study of pathways in humans and reveal network disruptions in autism Zikopoulos, Basilis; García-Cabezas, Miguel Ángel; Barbas, Helen (2018-02)Noninvasive imaging and tractography methods have yielded information on broad communication networks but lack resolution to delineate intralaminar cortical and subcortical pathways in humans. An important unanswered ...