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Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity

Standard

Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity. / Liska, Adam; Bertero, Alice; Gomolka, Ryszard; Sabbioni, Mara; Galbusera, Alberto; Barsotti, Noemi; Panzeri, Stefano; Scattoni, Maria Luisa; Pasqualetti, Massimo; Gozzi, Alessandro.

in: CEREB CORTEX, Jahrgang 28, Nr. 4, 01.04.2018, S. 1141-1153.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Liska, A, Bertero, A, Gomolka, R, Sabbioni, M, Galbusera, A, Barsotti, N, Panzeri, S, Scattoni, ML, Pasqualetti, M & Gozzi, A 2018, 'Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity', CEREB CORTEX, Jg. 28, Nr. 4, S. 1141-1153. https://doi.org/10.1093/cercor/bhx022

APA

Liska, A., Bertero, A., Gomolka, R., Sabbioni, M., Galbusera, A., Barsotti, N., Panzeri, S., Scattoni, M. L., Pasqualetti, M., & Gozzi, A. (2018). Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity. CEREB CORTEX, 28(4), 1141-1153. https://doi.org/10.1093/cercor/bhx022

Vancouver

Liska A, Bertero A, Gomolka R, Sabbioni M, Galbusera A, Barsotti N et al. Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity. CEREB CORTEX. 2018 Apr 1;28(4):1141-1153. https://doi.org/10.1093/cercor/bhx022

Bibtex

@article{8848f6e821e347b9891a136180d7375d,
title = "Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity",
abstract = "Functional connectivity aberrancies, as measured with resting-state functional magnetic resonance imaging (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, the genetic and neurobiological underpinnings of these findings remain unclear. Homozygous mutations in contactin associated protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to autism and epilepsy. Here we used rsfMRI to show that homozygous mice lacking Cntnap2 exhibit reduced long-range and local functional connectivity in prefrontal and midline brain {"}connectivity hubs.{"} Long-range rsfMRI connectivity impairments affected heteromodal cortical regions and were prominent between fronto-posterior components of the mouse default-mode network, an effect that was associated with reduced social investigation, a core {"}autism trait{"} in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex of Cntnap2-/- mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white-matter organization appeared to be otherwise preserved in these animals. These findings reveal a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.",
keywords = "Animals, Autistic Disorder/genetics, Brain Mapping, Diffusion Magnetic Resonance Imaging, Disease Models, Animal, Female, Image Processing, Computer-Assisted, Interpersonal Relations, Luminescent Proteins/genetics, Magnetic Resonance Imaging, Male, Membrane Proteins/genetics, Mice, Mice, Transgenic, Mutation/genetics, Nerve Net/diagnostic imaging, Nerve Tissue Proteins/genetics, Neural Pathways/diagnostic imaging, Oxygen/blood, Prefrontal Cortex/diagnostic imaging, Transduction, Genetic, White Matter/diagnostic imaging",
author = "Adam Liska and Alice Bertero and Ryszard Gomolka and Mara Sabbioni and Alberto Galbusera and Noemi Barsotti and Stefano Panzeri and Scattoni, {Maria Luisa} and Massimo Pasqualetti and Alessandro Gozzi",
year = "2018",
month = apr,
day = "1",
doi = "10.1093/cercor/bhx022",
language = "English",
volume = "28",
pages = "1141--1153",
journal = "CEREB CORTEX",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "4",

}

RIS

TY - JOUR

T1 - Homozygous Loss of Autism-Risk Gene CNTNAP2 Results in Reduced Local and Long-Range Prefrontal Functional Connectivity

AU - Liska, Adam

AU - Bertero, Alice

AU - Gomolka, Ryszard

AU - Sabbioni, Mara

AU - Galbusera, Alberto

AU - Barsotti, Noemi

AU - Panzeri, Stefano

AU - Scattoni, Maria Luisa

AU - Pasqualetti, Massimo

AU - Gozzi, Alessandro

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Functional connectivity aberrancies, as measured with resting-state functional magnetic resonance imaging (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, the genetic and neurobiological underpinnings of these findings remain unclear. Homozygous mutations in contactin associated protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to autism and epilepsy. Here we used rsfMRI to show that homozygous mice lacking Cntnap2 exhibit reduced long-range and local functional connectivity in prefrontal and midline brain "connectivity hubs." Long-range rsfMRI connectivity impairments affected heteromodal cortical regions and were prominent between fronto-posterior components of the mouse default-mode network, an effect that was associated with reduced social investigation, a core "autism trait" in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex of Cntnap2-/- mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white-matter organization appeared to be otherwise preserved in these animals. These findings reveal a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.

AB - Functional connectivity aberrancies, as measured with resting-state functional magnetic resonance imaging (rsfMRI), have been consistently observed in the brain of autism spectrum disorders (ASD) patients. However, the genetic and neurobiological underpinnings of these findings remain unclear. Homozygous mutations in contactin associated protein-like 2 (CNTNAP2), a neurexin-related cell-adhesion protein, are strongly linked to autism and epilepsy. Here we used rsfMRI to show that homozygous mice lacking Cntnap2 exhibit reduced long-range and local functional connectivity in prefrontal and midline brain "connectivity hubs." Long-range rsfMRI connectivity impairments affected heteromodal cortical regions and were prominent between fronto-posterior components of the mouse default-mode network, an effect that was associated with reduced social investigation, a core "autism trait" in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex of Cntnap2-/- mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white-matter organization appeared to be otherwise preserved in these animals. These findings reveal a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.

KW - Animals

KW - Autistic Disorder/genetics

KW - Brain Mapping

KW - Diffusion Magnetic Resonance Imaging

KW - Disease Models, Animal

KW - Female

KW - Image Processing, Computer-Assisted

KW - Interpersonal Relations

KW - Luminescent Proteins/genetics

KW - Magnetic Resonance Imaging

KW - Male

KW - Membrane Proteins/genetics

KW - Mice

KW - Mice, Transgenic

KW - Mutation/genetics

KW - Nerve Net/diagnostic imaging

KW - Nerve Tissue Proteins/genetics

KW - Neural Pathways/diagnostic imaging

KW - Oxygen/blood

KW - Prefrontal Cortex/diagnostic imaging

KW - Transduction, Genetic

KW - White Matter/diagnostic imaging

U2 - 10.1093/cercor/bhx022

DO - 10.1093/cercor/bhx022

M3 - SCORING: Journal article

C2 - 28184409

VL - 28

SP - 1141

EP - 1153

JO - CEREB CORTEX

JF - CEREB CORTEX

SN - 1047-3211

IS - 4

ER -