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

terial, 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.


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

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