Vogt, D., Cho, K. K. A., Shelton, S. M., Paul, A., Huang, Z. J., Sohal, V. S., Rubenstein, J. L. R. (September 2017) Mouse Cntnap2 and Human CNTNAP2 ASD Alleles Cell Autonomously Regulate PV+ Cortical Interneurons. Cereb Cortex, 28 (11). pp. 3868-3879. ISSN 1047-3211
Abstract
Human mutations in CNTNAP2 are associated with an array of neuropsychiatric and neurological syndromes, including speech and language disorders, epilepsy, and autism spectrum disorder (ASD). We examined Cntnap2's expression and function in GABAergic cortical interneurons (CINs), where its RNA is present at highest levels in chandelier neurons, PV+ neurons and VIP+ neurons. In vivo functions were studied using both constitutive Cntnap2 null mice and a transplantation assay, the latter to assess cell autonomous phenotypes of medial ganglionic eminence (MGE)-derived CINs. We found that Cntnap2 constitutive null mutants had normal numbers of MGE-derived CINs, but had reduced PV+ CINs. Transplantation assays showed that Cntnap2 cell autonomously regulated the physiology of parvalbumin (PV)+, fast-spiking CINs; no phenotypes were observed in somatostatin+, regular spiking, CINs. We also tested the effects of 4 human CNTNAP2 ASD missense mutations in vivo, and found that they impaired PV+ CIN development. Together, these data reveal that reduced CNTNAP2 function impairs PV+ CINs, a cell type with important roles in regulating cortical circuits.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > tissues types and functions > cerebral cortex organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons |
| CSHL Authors: | |
| Communities: | CSHL labs > Huang lab |
| Depositing User: | Matt Covey |
| Date: | 28 September 2017 |
| Date Deposited: | 25 Oct 2017 20:15 |
| Last Modified: | 14 Feb 2020 15:32 |
| PMCID: | PMC6455910 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/35572 |
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