Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder

Daniel A. Nagode, Xiangying Meng, Daniel E. Winkowski, Ed Smith, Hamza Khan-Tareen, Vishnupriya Kareddy, Joseph P.Y. Kao, Patrick Kanold

Research output: Contribution to journalArticle

Abstract

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. 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.

Original languageEnglish (US)
Pages (from-to)1100-1108
Number of pages9
JournalCell Reports
Volume18
Issue number5
DOIs
StatePublished - Jan 31 2017
Externally publishedYes

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Keywords

  • autism
  • cortex
  • development
  • subplate
  • valproate

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nagode, D. A., Meng, X., Winkowski, D. E., Smith, E., Khan-Tareen, H., Kareddy, V., Kao, J. P. Y., & Kanold, P. (2017). Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder. Cell Reports, 18(5), 1100-1108. https://doi.org/10.1016/j.celrep.2017.01.006