Memory study on mice offers new insights into understanding autism, NYU, Baylor

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http://www.eurekalert.org/pub_releases/2008-12/nyu-mso120308.php

Memory study on mice offers new insights into understanding autism,

NYU, Baylor scientists conclude

Researchers at New York University's Center for Neural Science and

the Baylor College of Medicine have identified a protein that when

removed from mice results in behaviors that are akin to those with

autism and obsessive-compulsive disorders. Their findings, which

appear in the latest issue of the journal Neuron, may enhance our

understanding of these and other neurological disorders.

The protein FKBP12, found in both humans and mice, is known to

regulate mTOR, an enzyme involved in synaptic plasticity, or the

ability of the neurons to change the collective strength of their

connections with other neurons. Learning and memory are believed to

result from changes in synaptic strength. mTOR also plays a role in

behavioral plasticity—the ability to alter behavior in response to

environmental changes.

The researchers eliminated FKBP12 from the brains of mice late in

development and subsequently examined them for alterations in

synaptic plasticity—specifically, in a brain area required for memory—

and their behaviors. To test how different types of memory were

affected by the absence of FKBP12, the NYU and Baylor scientists ran

the mice through a variety of mazes and observed how they responded

to certain objects.

The absence of the protein produced striking neurological and

behavioral changes in the studied mice. Their results showed

increased mTOR signaling, which regulates protein translation. This

indicates that FKBP12 acts to limit mTOR activity. The researchers

also found that the mice had enhanced synaptic plasticity and

contextual memory, suggesting that FKBP12 negatively regulates these

processes.

However, based on additional behavioral studies, the researchers

concluded that the brain's inability to properly regulate the

activity of mTOR may have dire consequences. These findings showed

that the mice had enhanced perseveration—that is, once they learned a

task, such as how to navigate a maze, they had difficulty learning

how to navigate a different version of the maze. They also displayed

enhanced repetitive behaviors and were more likely to interact with

familiar objects than they were with novel objects. These are

behaviors often found in individuals suffering from autism and other

neurological disorders.

" Our results suggest that FKBP12 regulates neuron signaling that

curbs the manifestation of traits observed in several neurological

disorders including autism, obsessive-compulsive disorder, and

schizophrenia, " said Klann, an NYU neuroscientist and the lead

researcher of the study. " Perseverative and repetitive behaviors

associated with these neurological disorders are widely believed to

be developmentally established—determined in utero by genetic,

hormonal, and environmental factors. Because our study indicates that

postnatal release of mTOR activity can result in certain

perseverative behaviors, it challenges the idea that some aspects of

these conditions are developmentally predetermined. "

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The research was supported by a grant from the National Institutes of

Health.