Traduction partielle : G.M.
Cell Rep. 2017 Jan 31;18(5):1100-1108. doi: 10.1016/j.celrep.2017.01.006.
Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder
Nagode DA1, Meng X1, Winkowski DE1, Smith E1, Khan-Tareen H1, Kareddy V1, Kao JP2, Kanold PO3.
Author information
- 1Department of Biology, University of Maryland, College Park, MD 20742, USA.
- 2Center for Biomedical Engineering and Technology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
- 3Department of Biology, University of Maryland, College Park, MD 20742, USA. Electronic address: pkanold@umd.edu
Abstract
Le trouble du spectre de l'autisme (TSA) implique des déficits dans le traitement de la parole et du son. Les changements de circuit corticaux au cours du développement précoce contribuent probablement à de tels déficits. Les
neurones sous plaques (SPN) forment les premiers microcircuits
corticaux et sont nécessaires au développement typique des circuits
thalamocorticaux et intracorticaux. L'acide
valproïque prénatal (VPA) augmente le risque de TSA, en particulier
lorsqu'il est présent pendant une période de temps critique coïncidant
avec la genèse de SPN.
Autism spectrum disorder (ASD) involves deficits in speech and sound processing. Cortical circuit changes during early development likely contribute to such deficits. Subplate neurons (SPNs) form the earliest cortical microcircuits and are required for normal development of thalamocortical and intracortical circuits. Prenatal valproic acid (VPA) increases ASD risk, especially when present during a critical time window coinciding with SPN genesis.
Using optical circuit mapping in mouse auditory cortex, we find that VPA exposure on E12 altered the functional excitatory and inhibitory connectivity of SPNs. Circuit changes manifested as "patches" of mostly increased connection probability or strength in the first postnatal week and as general hyper-connectivity after P10, shortly after ear opening.
Ces résultats suggèrent que l'exposition prénatale au VPA affecte gravement la trajectoire du développement des circuits corticaux et que l'activité sensorielle peut exacerber les déficits antérieurs et subtils de la connectivité. Nos résultats identifient la sous-plaque comme un éventuel substrat pathophysiologique commun des déficits dans le TSA.
These results suggest that prenatal VPA exposure severely affects the developmental trajectory of cortical circuits and that sensory-driven activity may exacerbate earlier, subtle connectivity deficits. Our findings identify the subplate as a possible common pathophysiological substrate of deficits in ASD.
Autism spectrum disorder (ASD) involves deficits in speech and sound processing. Cortical circuit changes during early development likely contribute to such deficits. Subplate neurons (SPNs) form the earliest cortical microcircuits and are required for normal development of thalamocortical and intracortical circuits. Prenatal valproic acid (VPA) increases ASD risk, especially when present during a critical time window coinciding with SPN genesis.
Using optical circuit mapping in mouse auditory cortex, we find that VPA exposure on E12 altered the functional excitatory and inhibitory connectivity of SPNs. Circuit changes manifested as "patches" of mostly increased connection probability or strength in the first postnatal week and as general hyper-connectivity after P10, shortly after ear opening.
Ces résultats suggèrent que l'exposition prénatale au VPA affecte gravement la trajectoire du développement des circuits corticaux et que l'activité sensorielle peut exacerber les déficits antérieurs et subtils de la connectivité. Nos résultats identifient la sous-plaque comme un éventuel substrat pathophysiologique commun des déficits dans le TSA.
These results suggest that prenatal VPA exposure severely affects the developmental trajectory of cortical circuits and that sensory-driven activity may exacerbate earlier, subtle connectivity deficits. Our findings identify the subplate as a possible common pathophysiological substrate of deficits in ASD.
Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
- PMID: 28147267
- DOI: 10.1016/j.celrep.2017.01.006
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