Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a Mouse Model of 16p11.2 Deletion Syndrome

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2014 May 6

PMID 24794428

Citations 135

Authors

Thomas Portmann

Mu Yang

Rong Mao

Georgia Panagiotakos

Jacob Ellegood

Gul Dolen

Patrick L Bader

Brad A Grueter

Carleton Goold

Elaine Fisher

Katherine Clifford

Pavitra Rengarajan

David Kalikhman

Darren Loureiro

Nay L Saw

Zhou Zhengqui

Michael A Miller

Jason P Lerch

Mark Henkelman

Mehrdad Shamloo

Robert C Malenka

Jacqueline N Crawley

Ricardo E Dolmetsch

Affiliations

Soon will be listed here.

Abstract

A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism.

Citing Articles

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