Summary: Researchers report the elimination of some receptor genes may lead to OCD-like behaviors.

Source: Northwestern University.

Elimination of certain receptor genes led to obsessive-compulsive disorder traits.

A new Northwestern Medicine study found evidence suggesting how neural dysfunction in a certain region of the brain can lead to obsessive and repetitive behaviors much like obsessive-compulsive disorder (OCD).

Both in humans and in mice, there is a circuit in the brain called the corticostriatal connection that regulates habitual and repetitive actions. The study found certain synaptic receptors are important for the development of this brain circuit. If these receptors are eliminated in mice, they exhibit obsessive behavior, such as over-grooming.

This is the first strong evidence that supports the biological basis for how these genes that code for these receptors might affect obsessive or compulsive behaviors in humans. By demonstrating that these receptors have this role in development, researchers down the line will have a target to develop treatments for obsessive-compulsive behavior.

“Variations in these receptor genes are associated with human neurodevelopmental disorders, such as autism and neuropsychiatric disorders such as OCD,” said lead author Anis Contractor, associate professor of physiology at Northwestern University Feinberg School of Medicine. “People with OCD are known to have abnormalities in function of corticostriatal circuits.”

The study was published February 21 in the journal Cell Reports. The findings shed light on the importance of these receptors in the formation of the corticostriatal circuits, Contractor said.

“A number of studies have found mutations in the kainate receptor genes that are associated with OCD or other neuropsychiatric and neurodevelopmental disorders in humans,” said Contractor, who also is an associate professor of neurobiology at the Weinberg College of Arts and Sciences at Northwestern. “I believe our study, which found that a mouse with targeted mutations in these genes exhibited OCD-like behaviors, helps support the current genetic studies on neuropsychiatric and neurodevelopmental disorders in humans.”

The traits of OCD the mice in the study exhibited included over-grooming, continuously digging in their bedding and consistently failing a simple alternating-choice test in a maze.

About this genetics research article

Other Northwestern authors include Jian Xu, John Marshall, Herman Fernandes, Toshihiro Nomura, Bryan Copits, Danielle Procissi, Lei Wang and Geoff Swanson.

Funding: This study was funded by the following grants from the National Institutes of Health (NIH): National Institute of Mental Health grant R01MH099114; National Institute of Neurological Disorders and Stroke (NINDS) grant R21NS082785 and the McKnight Foundation (to A.C.); and NINDS grant R01NS071952 to G.T.S. J.J.M. was supported by a fellowship from NIMH grant 1F31MH099807, and J.X. was supported by NIMH grant K01MH094464.

Source: Ziba Kashef – Northwestern University

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Full open access research for “Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice” by Jian Xu, John J. Marshall, Herman B. Fernandes, Toshihiro Nomura, Bryan A. Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T. Swanson, and Anis Contractor in Cell Reports. Published online February 1 2017 doi:10.1016/j.celrep.2017.01.073

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Northwestern University “OCD Like Behavior Linked to Genetic Mutation.” NeuroscienceNews. NeuroscienceNews, 23 February 2017.

<https://neurosciencenews.com/ocd-genetics-6150/>.[/cbtab][cbtab title=”APA”]Northwestern University (2017, February 23). OCD Like Behavior Linked to Genetic Mutation. NeuroscienceNew. Retrieved February 23, 2017 from https://neurosciencenews.com/ocd-genetics-6150/[/cbtab][cbtab title=”Chicago”]Northwestern University “OCD Like Behavior Linked to Genetic Mutation.” https://neurosciencenews.com/ocd-genetics-6150/ (accessed February 23, 2017).[/cbtab][/cbtabs]

Abstract

Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice



Highlights

•Mice with loss of all five kainate receptor genes have striatal-dependent phenotypes

•Mutant mice display perseverative and compulsive behavior and locomotor deficits

•Synapses onto striatal neurons have morphological and functional deficits

Summary

Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits. There were deficits in corticostriatal input to spiny projection neurons (SPNs) in the dorsal striatum and correlated reductions in spine density. The behavioral alterations were not present in mice only lacking the primary receptor subunit expressed in adult striatum (GluK2 KO), suggesting that signaling through multiple receptor types is required for proper striatal function. This demonstrates that alterations in striatal function dominate the behavioral phenotype in mice without kainate receptors.

“Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice” by Jian Xu, John J. Marshall, Herman B. Fernandes, Toshihiro Nomura, Bryan A. Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T. Swanson, and Anis Contractor in Cell Reports. Published online February 1 2017 doi:10.1016/j.celrep.2017.01.073

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