Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes

Aya Ishida, Kerstin Ure, Hongmei Chen, John W. Swann, Huda Y. Zoghbi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors.

Original languageEnglish
Pages (from-to)651-658
Number of pages8
JournalNeuron
Volume88
Issue number4
DOIs
Publication statusPublished - 2015 Nov 18
Externally publishedYes

Fingerprint

Rett Syndrome
Parvalbumins
Somatostatin
Phenotype
Neurons
Memory Disorders
Motor Neurons
Autistic Disorder
Schizophrenia
Seizures
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes. / Ishida, Aya; Ure, Kerstin; Chen, Hongmei; Swann, John W.; Zoghbi, Huda Y.

In: Neuron, Vol. 88, No. 4, 18.11.2015, p. 651-658.

Research output: Contribution to journalArticle

Ishida, Aya ; Ure, Kerstin ; Chen, Hongmei ; Swann, John W. ; Zoghbi, Huda Y. / Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes. In: Neuron. 2015 ; Vol. 88, No. 4. pp. 651-658.
@article{332e4c9d2f034af092540e545abfe6cc,
title = "Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes",
abstract = "Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors.",
author = "Aya Ishida and Kerstin Ure and Hongmei Chen and Swann, {John W.} and Zoghbi, {Huda Y.}",
year = "2015",
month = "11",
day = "18",
doi = "10.1016/j.neuron.2015.10.029",
language = "English",
volume = "88",
pages = "651--658",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes

AU - Ishida, Aya

AU - Ure, Kerstin

AU - Chen, Hongmei

AU - Swann, John W.

AU - Zoghbi, Huda Y.

PY - 2015/11/18

Y1 - 2015/11/18

N2 - Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors.

AB - Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors.

UR - http://www.scopus.com/inward/record.url?scp=84959361431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959361431&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2015.10.029

DO - 10.1016/j.neuron.2015.10.029

M3 - Article

C2 - 26590342

AN - SCOPUS:84959361431

VL - 88

SP - 651

EP - 658

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 4

ER -