Featured Research

from universities, journals, and other organizations

Impaired brain connections traced to schizophrenia mutation; Like patients, engineered mice falter at working memory tasks

Date:
April 1, 2010
Source:
NIH/National Institute of Mental Health
Summary:
The strongest known recurrent genetic cause of schizophrenia impairs communications between the brain's decision-making and memory hubs, resulting in working memory deficits, a study in mice has found. The new animal model shows how genetics affects brain circuitry, at the level of single neurons, to produce a core feature of the disorder.

To receive a reward, a mouse in the T-maze had to remember whether it had turned left or right on the previous trial, and turn in the opposite direction. Mice genetically engineered to lack a specific segment of genetic material on Chromosome 22, a known cause of schizophrenia -- like patients with the disorder -- faltered at such working memory tasks, because of poor functional connections between the brain's executive and memory hubs.
Credit: Torfi Sigurdsson, PhD, Department of Psychiatry, Columbia University

The strongest known recurrent genetic cause of schizophrenia impairs communications between the brain's decision-making and memory hubs, resulting in working memory deficits, according to a study in mice.

"For the first time, we have a powerful animal model that shows us how genetics affects brain circuitry, at the level of single neurons, to produce a learning and memory deficit linked to schizophrenia," explained Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), part of the National Institutes of Health. "This new research tool holds promise for ultimately unraveling the underlying anatomical connections and specific genes involved."

NIMH grantees Joshua Gordon, M.D., Ph.D., Joseph Gogos, M.D., Ph.D., Maria Karayiorgou, M.D., and Columbia University colleagues, report on their discovery in genetically engineered mice in the April 1, 2010 issue of the journal Nature.

"Our findings pinpoint a specific circuit and mechanism by which a mutation produces a core feature of the disorder," said Gordon, who led the research.

Researchers have suspected such a brain connectivity disturbance in schizophrenia for more than a century, and the NIH has launched a new initiative on the brain's functional circuitry, or connectome. Although the disorder is thought to be 70 percent heritable, its genetics are dauntingly complex, except in certain rare cases, such as those traced to the mutation in question.

Prior to this study, neuroimaging studies in schizophrenia patients had found abnormal connections between the brain's prefrontal cortex, the executive hub, and the hippocampus, the memory hub, linked to impaired working memory. It was also known that a mutation in the suspect site on chromosome 22, called 22q11.2, boosts schizophrenia risk 30-fold and also causes other abnormalities). Although accounting for only a small portion of cases, this tiny missing section of genetic material, called a microdeletion, has repeatedly turned up in genetic studies of schizophrenia and is an indisputable risk factor for the illness.

Still, the mutation's link to the disturbed connectivity and working memory deficit eluded detection until now.

To explore the mutation's effects on brain circuitry, Gogos, Karayiorgou and colleagues engineered a line of mice expressing the same missing segment of genetic material as the patients. Strikingly, like their human counterparts with schizophrenia, these animals turned out to have difficulty with working memory tasks -- holding information in mind from moment to moment.

Successful performance of such tasks depends on good connections in a circuit linking the prefrontal cortex and the hippocampus. To measure such functional connections, Gordon and colleagues monitored signals emitted by single neurons implanted in the two distant brain structures while mice performed a working memory task in a T-maze (see below).

The more in-sync the neurons from the two areas fired, the better the functional connections between the two structures -- and the better the mice performed the task. Moreover, the better the synchrony to start with, the quicker the animals learned the task. The more synchrony improved, the better they performed.

As suspected, the mice with the chromosome 22 mutation faltered on all counts -- showing much worse synchrony, learning and performance levels than control mice.

"Our results extend beyond those in patients by showing how an undeniable genetic risk factor for schizophrenia can disrupt connectivity at the level of single neurons," explained Gordon.

The researchers plan to follow up with studies into how the mutation affects brain anatomical and molecular connections and the workings of affected genes.

The research was also funded by the Simons Foundation.


Story Source:

The above story is based on materials provided by NIH/National Institute of Mental Health. Note: Materials may be edited for content and length.


Journal Reference:

  1. Torfi Sigurdsson, Kimberly L. Stark, Maria Karayiorgou, Joseph A. Gogos, Joshua A. Gordon. Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia. Nature, 2010; 464 (7289): 763 DOI: 10.1038/nature08855

Cite This Page:

NIH/National Institute of Mental Health. "Impaired brain connections traced to schizophrenia mutation; Like patients, engineered mice falter at working memory tasks." ScienceDaily. ScienceDaily, 1 April 2010. <www.sciencedaily.com/releases/2010/03/100331161623.htm>.
NIH/National Institute of Mental Health. (2010, April 1). Impaired brain connections traced to schizophrenia mutation; Like patients, engineered mice falter at working memory tasks. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2010/03/100331161623.htm
NIH/National Institute of Mental Health. "Impaired brain connections traced to schizophrenia mutation; Like patients, engineered mice falter at working memory tasks." ScienceDaily. www.sciencedaily.com/releases/2010/03/100331161623.htm (accessed October 21, 2014).

Share This



More Mind & Brain News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
Portable Breathalyzer Gets You Home Safely

Portable Breathalyzer Gets You Home Safely

Buzz60 (Oct. 21, 2014) Breeze, a portable breathalyzer, gets you home safely by instantly showing your blood alcohol content, and with one tap, lets you call an Uber, a cab or a friend from your contact list to pick you up. Sean Dowling (@SeanDowlingTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Your Birth Season Might Determine Your Temperament

Your Birth Season Might Determine Your Temperament

Newsy (Oct. 20, 2014) A new study says the season you're born in can determine your temperament — and one season has a surprising outcome. Video provided by Newsy
Powered by NewsLook.com
Movies Might Desensitize Violence For Parents, Not Just Kids

Movies Might Desensitize Violence For Parents, Not Just Kids

Newsy (Oct. 20, 2014) A study suggests that parents become desensitized to violent movies as well as children, which leads them to allow their kids to view violent films. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins