Researchers Pinpoint Root of Fear in Mice Brains

A missing brain protein has been linked with how laboratory mice process fear, and researchers hope that the find will lead to future breakthroughs in human neurological research.

Researchers from the University of Southern California examined mice without the neurotransmitting enzymes monoamine oxidase A and B (MAO A/B), which sit next to each other in a human's genetic code as well as on that of mice.

Previous research indicated an association between deficiencies in MAO A/B enzymes with clinical disabilities along the autism spectrum, including the inability to change or modulate actions along with social context.

Jean Shih, the lead researcher in the study said the mice may serve as a model to develop an intervention to neuropsychiatric disorders such as aggression or anxiety.

"The severity of the changes in the MAO A/B knockout mice compared to MAO A knockout mice supports the idea that the severity of autistic-like features may be correlated to the amounts of monoamine levels, particularly at early developmental stages," Shih said.

When comparing mice the MAO A/B enzymes removed with their wild, unaltered littermates, the researchers found significant differences in how the mice without MAO A/B processed fear and other types of learning.

For the experiment, mice without MAO A/B and wild mice were placed in a neutral environment and given an electric shock. All mice in the experiment showed learned fear the next time they were tested in the same environment, but the mice without MAO A/B displayed a greater degree of fear, the researchers report.

The next step of the experiment revealed that wild mice would freely explore new environmenrts, even after the initial trauma of electric shock. But mice without the MAO A/B enzymes allowed their fear of the shock to carry over into the new context, even when there was no clear reason for the mice 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."

Mice without MAO A/B did not show any differences in learning for spatial skills and object recognition, which the rsearchers note is a key factor. But Singh said that regarding the ability to learn an emotional event, MAO A/B-less mice are "very different than wild types."

"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," Singh said.

The study is published in the journal Proceedings of the National Academy of Sciences.