New Experiments Show Genes Play Significant Role In Fear

October 27, 1997

A group of faculty, graduate and undergraduate students at the University of Colorado at Boulder have found new evidence that genes play a key role in individual differences regarding fear-related learning in a study of two genetic strains of mice.

Twin studies in humans have provided evidence for a "substantial genetic component" underlying differences in susceptibility to extreme reactions to fear-inducing events, said Jeanne Wehner, a professor at CU-Boulder's Institute for Behavioral Genetics. "Our primary interest is individual differences in learning and memory," she said. "Animal models allow us to map the genes much more quickly and easily."

In a series of experiments, the CU researchers exposed two strains of mice to light electroshocks in conjunction with an audible clicking sound. Since the primary fear reaction of mice is to freeze, each rodents' freezing behavior was charted when the animals were later subjected to the clicking sound alone, to the environment in which the sound and shock were administered together, and in an altered physical environment, Wehner said.

The researchers identified the genetic links by analyzing genetic similarities and differences between mice exhibiting extreme fear conditioning with mice exhibiting significantly less fear. The strongest link was on a portion of chromosome 1, which may contain hundreds of genes, she said. There also were weaker links to chromosomes 10 and 16.

The genetic research has implications for human disorders like post-traumatic stress, assuming researchers can pinpoint analogous genes for fear conditioning in humans, she said. New pharmacological agents developed specifically to target human genes implicated in fear-related disorders could be used in treating a variety of human emotional problems.

A paper on the subject by CU-Boulder's Wehner, Richard Radcliffe, Shelby Rosman, Steven Christiansen, Duffy Rassmussen, David Fulker and Michelle Wiles appears in the November 1997 issue of Nature Genetics.

The group used 84 DNA markers, unique chemical road signs on each chromosome that allow researchers to track associated genes. CU researchers have begun sequencing the genes in a search for likely candidates.

A companion paper in the November issue of Nature Genetics by a group from the State Department of Health in Albany, N.Y., also concluded chromosome 1 was significantly involved in fear conditioning in mice.

The same region of chromosome 1 was implicated in a 1995 study by Oxford University's Jonathan Flint and CU-Boulder's John DeFries, David Fulker and Allan Collins. The study focused on emotionality in mice following a series of experiments that exposed mice to brightly lit open areas.

In addition, a 1997 study by an international research team led by Howard Gershenfeld of the University of Texas Southwestern Medical Center in Dallas showed similar results. "There are now four separate studies on fear responses in animals that implicate this portion of chromosome 1," said Wehner, whose research is funded by NIH. "The thing we need to do now is get at the gene or genes involved."

In 1992, Wehner was part of a national team that identified a gene associated with spatial learning in mice. "We are very interested in complex learning behavior," she said. "In this case we chose the fear-conditioning component for testing as a way to try and understand individual genetic differences in learning."

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University of Colorado at Boulder

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