Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder.
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.
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Daniel A
DA
Nagode
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Xiangying
X
Meng
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Daniel E
DE
Winkowski
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Ed
E
Smith
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Hamza
H
Khan-Tareen
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Vishnupriya
V
Kareddy
Center for Biomedical Engineering and Technology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Joseph P Y
JPY
Kao
Department of Biology, University of Maryland, College Park, MD 20742, USA. Electronic address: pkanold@umd.edu.
Patrick O
PO
Kanold
D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000503:physiopathology*; D000067877:Autism Spectrum Disorder / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D013788:Thalamus / Q000378:metabolism / Q000503:physiopathology; D014635:Valproic Acid / Q000378:metabolism
D014635:Valproic Acid
autism; cortex; development; subplate; valproate