Behavioral and Synaptic Circuit Features in a Zebrafish Model of Fragile X Syndrome

Ming Chong Ng, Yi Ling Yang, Kwok Tung Lu

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Fragile X syndrome (FXS) is the most frequent inherited form of human mental retardation. It is characterized by cognitive impairment and physical and behavioral problems and is caused by the silencing of fmr1 transcription and the absence of the fmr1 protein (FMRP). Recently, animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanisms of this loss-of-function disorder. The present study was aimed to further characterize the role of FMRP in behavior and synaptic function by using fmr1 knockout zebrafish. In adult zebrafish, we found that fmr1 knockout produces the anxiolytic-like responses of increased exploratory behavior in light/dark and open-field tests and avoidance learning impairment. Furthermore, electrophysiological recordings from telencephalic slice preparations of knockout fish displayed markedly reduced long-term potentiation and enhanced long-term depression compared to wild-type fish; however, basal glutamatergic transmission and presynaptic function at the lateral (Dl) and medial (Dm) division of the dorsal telencephalon synapse remained normal. Taken together, our study not only evaluates the mechanism of FRMP but also suggests that zebrafish have valuable potential as a complementary vertebrate model in studying the molecular pathogenesis of human fragile X syndrome.

Original languageEnglish
Article numbere51456
JournalPloS one
Volume8
Issue number3
DOIs
Publication statusPublished - 2013 Mar 11

Fingerprint

Fragile X Syndrome
Zebrafish
Danio rerio
Telencephalon
Fish
Networks (circuits)
Fishes
Avoidance Learning
tranquilizers
behavior problems
molecular models
Exploratory Behavior
Long-Term Potentiation
Anti-Anxiety Agents
Transcription
synapse
fish
Intellectual Disability
Synapses
Vertebrates

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Behavioral and Synaptic Circuit Features in a Zebrafish Model of Fragile X Syndrome. / Ng, Ming Chong; Yang, Yi Ling; Lu, Kwok Tung.

In: PloS one, Vol. 8, No. 3, e51456, 11.03.2013.

Research output: Contribution to journalArticle

@article{b43c560bcc874381b61a8b1c818cfc04,
title = "Behavioral and Synaptic Circuit Features in a Zebrafish Model of Fragile X Syndrome",
abstract = "Fragile X syndrome (FXS) is the most frequent inherited form of human mental retardation. It is characterized by cognitive impairment and physical and behavioral problems and is caused by the silencing of fmr1 transcription and the absence of the fmr1 protein (FMRP). Recently, animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanisms of this loss-of-function disorder. The present study was aimed to further characterize the role of FMRP in behavior and synaptic function by using fmr1 knockout zebrafish. In adult zebrafish, we found that fmr1 knockout produces the anxiolytic-like responses of increased exploratory behavior in light/dark and open-field tests and avoidance learning impairment. Furthermore, electrophysiological recordings from telencephalic slice preparations of knockout fish displayed markedly reduced long-term potentiation and enhanced long-term depression compared to wild-type fish; however, basal glutamatergic transmission and presynaptic function at the lateral (Dl) and medial (Dm) division of the dorsal telencephalon synapse remained normal. Taken together, our study not only evaluates the mechanism of FRMP but also suggests that zebrafish have valuable potential as a complementary vertebrate model in studying the molecular pathogenesis of human fragile X syndrome.",
author = "Ng, {Ming Chong} and Yang, {Yi Ling} and Lu, {Kwok Tung}",
year = "2013",
month = "3",
day = "11",
doi = "10.1371/journal.pone.0051456",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Behavioral and Synaptic Circuit Features in a Zebrafish Model of Fragile X Syndrome

AU - Ng, Ming Chong

AU - Yang, Yi Ling

AU - Lu, Kwok Tung

PY - 2013/3/11

Y1 - 2013/3/11

N2 - Fragile X syndrome (FXS) is the most frequent inherited form of human mental retardation. It is characterized by cognitive impairment and physical and behavioral problems and is caused by the silencing of fmr1 transcription and the absence of the fmr1 protein (FMRP). Recently, animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanisms of this loss-of-function disorder. The present study was aimed to further characterize the role of FMRP in behavior and synaptic function by using fmr1 knockout zebrafish. In adult zebrafish, we found that fmr1 knockout produces the anxiolytic-like responses of increased exploratory behavior in light/dark and open-field tests and avoidance learning impairment. Furthermore, electrophysiological recordings from telencephalic slice preparations of knockout fish displayed markedly reduced long-term potentiation and enhanced long-term depression compared to wild-type fish; however, basal glutamatergic transmission and presynaptic function at the lateral (Dl) and medial (Dm) division of the dorsal telencephalon synapse remained normal. Taken together, our study not only evaluates the mechanism of FRMP but also suggests that zebrafish have valuable potential as a complementary vertebrate model in studying the molecular pathogenesis of human fragile X syndrome.

AB - Fragile X syndrome (FXS) is the most frequent inherited form of human mental retardation. It is characterized by cognitive impairment and physical and behavioral problems and is caused by the silencing of fmr1 transcription and the absence of the fmr1 protein (FMRP). Recently, animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanisms of this loss-of-function disorder. The present study was aimed to further characterize the role of FMRP in behavior and synaptic function by using fmr1 knockout zebrafish. In adult zebrafish, we found that fmr1 knockout produces the anxiolytic-like responses of increased exploratory behavior in light/dark and open-field tests and avoidance learning impairment. Furthermore, electrophysiological recordings from telencephalic slice preparations of knockout fish displayed markedly reduced long-term potentiation and enhanced long-term depression compared to wild-type fish; however, basal glutamatergic transmission and presynaptic function at the lateral (Dl) and medial (Dm) division of the dorsal telencephalon synapse remained normal. Taken together, our study not only evaluates the mechanism of FRMP but also suggests that zebrafish have valuable potential as a complementary vertebrate model in studying the molecular pathogenesis of human fragile X syndrome.

UR - http://www.scopus.com/inward/record.url?scp=84874854034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874854034&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0051456

DO - 10.1371/journal.pone.0051456

M3 - Article

C2 - 23536755

AN - SCOPUS:84874854034

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e51456

ER -