Spring 2020 Newsletter

Investigating how estrogens in the brain affect auditory learning

Matheus Macedo-Lima
Matheus Macedo-Lima ‘20PhD

Gaining a deeper understanding of how the human brain processes language is key to treating and preventing problems that affect our brain, body, and quality of life. Matheus Macedo-Lima ‘20PhD and faculty member Luke Remage-Healey have reported in a recent issue of Hormones and Behavior that estradiol (an estrogen) production in the auditory brain region of the adult male zebra finch is essential for the learning of new sounds.

From past research, the neuroscientists knew that hormones played a role in spatial learning–how an animal encodes information about their environment to facilitate navigation. Now they have discovered more about how hormones are involved in the development of our senses (visual, auditory, etc.). “This is the first time outside of the hippocampus that we show that in sensory processing, hormones are also important for learning,” says Macedo-Lima.

The zebra finch must learn how to sing from its parents, it doesn’t have this innate ability at birth. The Healey Lab studies the bird’s listening abilities—how sounds are heard, processed, and what regulates this part of the bird’s learning.

zebra finch flyingThe songbird brain has several regions dedicated to song learning and song production including the NCM (part of the bird auditory cortex). This brain region makes hormones such as estrogens, which is not a very common thing in the cortex of other animals. Humans and birds share a parallel in that humans also produce hormones in the language centers of the brain. These two different brain types diverged from other species and developed a common strategy to solve the problem of learning complex sounds.

The UMass researchers’ hypothesis was that hormone production might be related to the learning of general sounds in adult male zebra finches. These birds only sing one song for their whole life, they don’t learn new songs, but they still need to learn other sounds in their environment.

The team designed a way to test their hypothesis by capitalizing on one of the zebra finches’ natural behaviors, being very social with others in their flock. The researchers discovered that the birds would do tasks in order to get chances to socialize.

The setup of their experiment involved two finches in chambers separated by a sheet of smart glass that turns from opaque to transparent when an electrical charge is activated. Next, one bird was trained to complete a certain number of pecks on a red light in the middle of an infrared beam break, which would trigger the smart glass to show the second bird. The bird was excited to perform this action, doing it hundreds of times. The training progressed by prompting the bird to discriminate between two different sounds, give an answer in the form of pecks, and learn which sound would trigger the glass.

To test if estrogens affected their learning process, birds were given an aromatase inhibitor delivered directly into the NCM, which suppressed the production of estradiol. After the treatment, the researchers found that the birds were slower to learn. The researchers also found that oral administration of the drug made the birds less motivated to complete the task, affecting their sociality.

“We hope that this research will help [the scientific community] understand how hormones affect neurons. This is the first time that anyone has reported the effect of hormones on sensory learning,” states Macedo-Lima.

Aromatase inhibitors are commonly used in humans for the treatment of estrogen-sensitive illnesses like breast cancer. They work to slow down the cancer or prevent it from coming back. However, problematic side effects can occur like cognitive fog which can impede memory, learning, and navigation abilities.

The findings of Macedo-Lima and Remage-Healey suggest that estradiol is important for learning, and new therapies are needed that effectively prevent breast cancer recurrence while minimizing side effects that further compromise quality of life.

As part of his dissertation research, Macedo-Lima took his studies further, looking at how dopamine, a neuromodulator that changes neural circuits, could be involved in the learning process. He investigated how estradiol could be shaping dopamine neurotransmission in the NCM.

Macedo-Lima remarks, “These animals are our greatest shot at giving us an idea about how language works. This part of the encoding or listening presumably would be the first step to learning how to produce sounds. The part of the brain that we focus on there’s not much known, it’s fun to try to push this field closer to a more modern understanding.”

Read full paper in Hormones and Behavior