Navigation Links
Impaired brain connections traced to schizophrenia mutation
Date:3/31/2010

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.


'/>"/>

Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
Source:Eurekalert  

Related biology news :

1. Impaired transport in neurons triggers prion disease
2. Lack of happiness hormone serotonin in the brain causes impaired maternal behavior in mice
3. After a few drinks, older adults more impaired than they think
4. Impaired energy metabolism linked with initiation of plaques in Alzheimers brain
5. Scientists identify cell changes leading to impaired artificial kidney function
6. Telescope embedded in glasses lens promises to make driving easier for visually impaired
7. New brain nerve cells key to stress resilience, UT Southwestern researchers find
8. Insulin-like signal needed to keep stem cells alive in adult brain
9. New understanding of proteins role in brain
10. New period of brain plasticity created with transplanted embryonic cells
11. Sex on the brain: Doublesex gene key to determining fruit fly gender
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Impaired brain connections traced to schizophrenia mutation
(Date:2/3/2017)... A new independent identity strategy consultancy firm announces its ... to fill a critical niche in technical and policy ... Mark Crego and Janice Kephart together ... that span federal governments, the 9/11 Commission, private industry, ... has a common theme born from a shared passion ...
(Date:1/31/2017)... Jan. 31, 2017  Spero Therapeutics, LLC, a ... the treatment of bacterial infections, today announced it ... candidates from Pro Bono Bio Ltd (PBB) to ... multi-drug resistant forms of Gram-negative bacteria.   The assets ... Ltd, a PBB group company. "The ...
(Date:1/24/2017)... , Jan. 24, 2017 Biopharm ... of the laboratory use of nuclear magnetic resonance ... experienced end-users and profiled current practices, developments, trends ... as well as growth and opportunities. These areas ... suppliers, NMR instruments, needs and innovation requirements, hyphenated ...
Breaking Biology News(10 mins):
(Date:2/17/2017)... Feb. 17, 2017  If only one in ... a mutation-conferring resistance to chemotherapy, thousands of cancer ... has focused on finding these mutations in ever-smaller ... circulating tumor DNA in blood — to guide ... Unfortunately, however, detecting these genetic anomalies ...
(Date:2/16/2017)...  ImMAGE Biotherapeutics (OTCMKTS: IMMG), an early-stage biotechnology company harnessing ... treatment for triple negative breast cancer (TNBC), announced today their ... program. The YEi Start in ... entrepreneurs grow their business in France ... selected to complete an intensive one week immersion in ...
(Date:2/16/2017)... 2017   Capricor Therapeutics, Inc. (NASDAQ: ... developing first-in-class biological therapies for cardiac and other ... to terminate its license agreement with the Mayo ... Cenderitide. "Our decision to return these ... our efforts to advance our core cell and ...
(Date:2/16/2017)... , Feb. 16, 2017  Champions Oncology, Inc. ... the development and sale of advanced technology solutions and ... drugs, today announced the addition of new cohorts of ... These new models will expand Champions, product line in ... and neck cancer, AML, and non-small cell lung cancer ...
Breaking Biology Technology: