期刊
CEREBRAL CORTEX
卷 28, 期 11, 页码 3868-3879出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhx248
关键词
CNTNAP2; Cortical interneuron; fast-spiking; MGE; parvalbumin
资金
- UCSF CTSI Pilot grant [1111111]
- NIMH [1K99MH108720]
- CIRM [TB1-01190]
- BRAIN initiative [U01 MH105948]
- Nina Ireland
- NIMH R01 [MH081880]
- NIMH R37 [MH049428]
- Simons Foundation [309279]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据