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Fear factor: Missing brain enzyme leads to abnormal levels of fear in mice, reveals new research
Date:7/15/2013

MAO A/B, which regulates neurotransmitters known as monoamines, including serotonin, norepinephrine and dopamine.

Comparing mice without MAO A/B with their wild-type littermates, the researchers found significant differences in how the mice without MAO A/B processed fear and other types of learning. Mice without MAO A/B and wild mice were put in a new, neutral environment and given a mild electric shock. All mice showed learned fear the next time they were tested in the same environment, with the MAO A/B knockout mice displaying a greater degree of fear.

But while wild mice continued to explore other new environments freely after the trauma, mice without the MAO A/B enzymes generalized their phobia to other contexts their fear spilled over onto places where they should have no reason to be afraid.

"The neural substrates processing fear in the brain is very different in these mice," Singh said. "Enhanced learning in the wrong context is a disorder and is exemplified by these mice. Their brain is not letting them forget. In a survival issue, you need to be able to forget things."

The mice without MAO A and MAO B also learned eye-blink conditioning much more quickly than wild mice, which has also been noted in autistic patients but not in mice missing only one of these enzymes.

Importantly, the mice without MAO A/B did not display any differences in learning for spatial skills and object recognition, the researchers found, "but in their ability to learn an emotional event, the [MAO A/B knockout mice] are very different than wild types," Singh said.

He continued: "When both enzymes are missing, it significantly increases the levels of neurotransmitters, which causes developmental changes, which leads to differential expression of receptors that are very important for synaptic plasticity a measure of learning and to behavior that is quite similar to what we see along the autism spectrum."


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Contact: Suzanne Wu
suzanne.wu@usc.edu
213-740-0252
University of Southern California
Source:Eurekalert

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