The Role of the Lynx Gene in Learning and Behavior

A Genetic Brake

Young children absorb new information like sponges, says Julie Miwa. Language learning, for example, is easier for children than adults, who tend to require more training and practice. Neuroscientists call this young, robust period of learning in children "the period of plasticity."

"[The period of plasticity is] this window where not only do we learn a lot of information, but actually the connections in our brains are shaped and refined," explains Miwa, assistant professor of neuroscience. "So new connections are made, other connections are taken away, and that's to make the brain have a more accurate understanding of the external world that the individual experiences."

Unfortunately, like all good things, that period of plasticity usually comes to an end. This happens, says Miwa, thanks to the lynx1 gene.

Miwa discovered the gene as a graduate student at Rockefeller University, and she describes it as a "brake" on the critical period of plasticity. Lynx1 turns on at the end of the period of plasticity. Once that brake is applied, learning requires more work.

Miwa discovered that the removal or "knockout" of lynx1 through genetic engineering can extend the period of plasticity into adulthood. One element of her research focuses on how scientists might control the gene. Her animal studies have yielded compelling results.

Knocking out the lynx1 gene in mice results in better associative learning, says Miwa. These so-called "knockout mice" demonstrate an increased ability to make connections. Miwa believes that, similarly, humans with a mutation of the gene might retain the period of plasticity as adults.

"Maybe they're better able to make associations, maybe they're more open to new information because they can mold their synapses and wiring with more ease," she says.

To learn more about the lynx1 mutation in humans, Miwa and her team, aided by Almut Hupbach, professor of psychology, administer psychological tests to see how well human study participants learn, how open they are to new information and how creative they are. The team also extracts DNA from a saliva sample from each participant to determine if any participants have the lynx1 mutation. They then attempt to correlate mutations with advanced cognitive abilities. A portion of this research was conducted over the past two summers as part of Lehigh's Mountaintop program, a unique learning environment which allows students and faculty mentors the freedom to explore open-ended questions.

A better understanding of how to turn the lynx1 gene off might be particularly helpful in instances of stroke or Alzheimer's disease, says Miwa. If, for example, a stroke patient has suffered damage to the part of the brain that controls speech, a return to the period of plasticity might improve their ability to regain language. Likewise, Alzheimer's patients might see improvement in memory function.

Emotional Regulation

Just as lynx1 suppresses learning, another gene, lynx2, suppresses fear and anxiety. Lynx2 is expressed in the amygdala, the part of the brain that controls emotion. Miwa explores the role of lynx2 in emotional regulation and resilience to determine how humans adapt to a world in constant flux.

Lynx2 knockout mice demonstrate higher anxiety levels and are less willing to interact with other mice. In humans, Miwa says, a lynx2 mutation might affect not only an individual's anxiety level, but also the ability to socialize, impacting resilience and overall success.

"[A lynx2 mutation] can have a lot of negative effects on a person's ability to navigate the world," says Miwa. "I think it could have really substantial effects on an individual's success, their sense of well being, how they go through the world. I would like to move the project into areas like longitudinal studies [and go] out in the world to see how it affects people and their resilience over time."

The learning and behavior dimension of this lynx gene research is an extension of Miwa's regular research, which focuses on complex neurobiological processes in genetic mouse models and how they are regulated through the cholinergic system. The cholinergic system is a modulatory neurotransmitter system, which means it releases or responds to the neurotransmitter acetylcholine, and lynx genes are regulatory proteins over the specialized proteins acetylcholine binds to, nicotinic receptors of the cholinergic system. Moving beyond synaptic connections and genes, Miwa's outward-leaning, psychology-based approach to lynx might reveal much about human learning and behavior.

"The world is changing all the time, so it behooves us to be constantly adapting," she says. "[That] might be hard because we're outside the critical period [of plasticity]. So you can imagine then, if you can understand about turning on and off the gene, that we'd be better able to adapt to these new challenges."

This story appears as "A Genetic Brake" in the 2017 Lehigh Research Review.