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The Brain Team: finding ways to unlock the mysteries of the brain

brain-bow
One of Dr. Lorna Role’s office walls has six giant pictures, above, of “brainbow” brains—mice brains that are dyed with fluorescent proteins in order to differentiate between neighboring neurons. PHOTO CREDIT: BRIANA LIONETTI

This story was originally written as a part of the author’s senior project for the Stony Brook University School of Journalism’s bachelor degree program. The Statesman has republished the story with the permission of the author. A longer version can be read here.

At 18, Liz Ballinger’s younger brother Nick started to go blind. His grades began to decline in school and his mother grounded him—unaware that a tangle of blood vessels in his head was stealing blood from his eyes, which was causing the blindness. His mother stood in their kitchen, with two fingers up, and asked Nick how many fingers she was holding up.

He couldn’t correctly answer the question.

The bundle of arteries and veins in his brain was too big and deemed untreatable. But there was a new cancer treatment called proton-beam therapy, which was offered only two places in the world—one of those places being 45 minutes away from their home. The doctors performed the procedures, and all seemed well at the time.

But at 20, the tangle in Nick’s brain, called an arteriovenous malformation (AVM), had caused a massive brain hemorrhage and he was in an induced coma for a month. He went through numerous brain surgeries and therapy afterwards.

Nick Ballinger, 28, went from being legally blind to being able to drive. The only side effect Nick suffers from today is that he lost function of his left hand.

Nick’s illness not only changed his life but also altered the course of his sister’s life.

Today, Liz Ballinger, 30, is studying the brain as a part of a team of neuroscientists at Stony Brook University led by Dr. Lorna Role and Role’s husband, Dr. David Talmage. This team is trying to answer crucial questions that could potentially lead to treatments for brain diseases such as Parkinson’s, Alzheimer’s and PTSD.

The team’s work comes at a time when the government has poured millions into brain research. President Barack Obama announced the BRAIN Initiative in April 2013, with the intent of mapping the brain.

“Imagine if no family had to feel helpless watching a loved one disappear behind the mask of Parkinson’s or struggle in the grip of epilepsy,” Obama said during his BRAIN initiative speech. “Imagine if we could reverse traumatic brain injury or PTSD for our veterans coming home.”

The National Institutes of Health (NIH) estimates that five million Americans 65 and older currently have Alzheimer’s. In 2050, the disease is expected to affect 13.5 million people, according to the Alzheimer’s Association.

Role and Talmage head the Stony Brook team that has been pursuing questions such as: How do memories form? What happens to the brain when someone can no longer remember an important event or recognize a close family member? What happens to the brain when a memory becomes too massive to cope with?

The team set out to learn if there was a way, without using powerful drugs, to enhance or delete memories in diseases such as Alzheimer’s or PTSD.

Five years after the Role and Talmage lab was awarded an NIH grant in 2010 for its research, the team is at a crucial point in their research and believe they have some promising results that could help with the development of new “memory healing” applications in humans.

One of the biggest obstacles for team is understanding the normal brain. It is the most complex organ in the human body and home to approximately 100 billion brain cells, all with thousands of interconnections.

The human brain weighs approximately three pounds, which is only two percent of body’s weight, but it gobbles up more than 20 percent of the body’s daily energy.

“It’s remarkably efficient, all it needs is a little sugar to do billions of calculations each second,” Role said.

“When you study for an exam, you don’t end up with smoke coming out of your ears, do you?” Role added. “That’s because the brain’s is super energy efficient. Even where you are thinking really, really hard, your head doesn’t burst into flames.”

Role is the chair of the Department of Neurobiology and Behavior at Stony Brook and had a 25-year career at Columbia University prior to coming to Stony Brook. Her team, with Talmage, consists of about 20 undergraduates, doctoral students, post-doctoral students and career neuroscientists.

Ballinger originally wanted to study journalism when she went to college, but her brother’s disease was a turning point for her. She is now in medical school while pursuing her Ph.D. in neuroscience in the Role and Talmage lab.

She and Role are currently studying how recognition memory is altered in an autism-linked disease called Rett Syndrome, which almost exclusively affects girls. Ballinger wants to be a pediatric neurologist once she receives her M.D. and Ph.D.

Ballinger isn’t the only one in the Role and Talmage lab that has been motivated to study the brain for personal reasons. Alice Jone, another Ph.D. student in the lab, went into neuroscience after watching her mother-in-law suffer from bipolar disorder. She said that, aside from this disease ravaging her mother-in-law and family, she was disappointed in the shortcomings in the available medications and treatments.

“I’m hoping that whatever I find will bring us that much closer to understanding the mechanism for the disease and eventually lead to a development of more efficient drugs,” Jone said.

Team leaders Role and Talmage face challenges every day, ranging from keeping the research on track, to getting the findings published.  Their biggest challenge is continuing to raise money to support their work.

Ballinger and her colleagues use mice to study diseases that affect memory. For the past five years, the team has been experimenting with the amounts of natural chemicals in mouse brains to learn more about the fear responses in PTSD. The team has been exploring what occurs at the point where two neurons communicate with each other. Their current goal is to understand how learning and memory occur when an animal is in an emotionally-charged environment.

One of Role’s office walls has six giant pictures of “brainbow” brains—which are mice brains that are dyed with fluorescent proteins in order to differentiate between neighboring neurons. The neurons express a rainbow of colors.

On her desk, Role keeps a picture of her deceased parents and deceased brother who died of cancer. She said her parents are responsible for her interest in science and that her brother, Phillip, who had a career in internal medicine, was “larger than life.”

Dr. James Lederman, another researcher who trained in her lab, explained that part of their study involved tones and shocks to see how certain brain cells, called cholinergic neurons, are activated by fear. Cholinergic neurons use a neurotransmitter called acetylcholine. Neurons use neurotransmitters to transmit their messages to and from their neighbors at structures called synapses.

The researchers found that these cholinergic signals are an essential component of learning in a fearful environment and why fear memories last so long.

In 2010, Role won the NIH’s Pioneer Award, which awarded her $500,000 per year for five years to fund the lab’s research. The winners have to be “individuals of exceptional creativity proposing highly innovative research,” according to the NIH website.

The Role and Talmage lab is on the fifth floor of the Centers for Molecular Medicine building on Stony Brook’s west campus. The lab’s outside perimeter is lined with windows that illuminate the team’s lab benches and microscopes. The lab stations have the usual beakers and bottles with various solutions, and some have instruments that allow the researchers to slice brains into precise proportions and to record the electrical activity at individual synapses.

All of the Role and Talmage team members have individual projects that are linked by common interests in how the brain works in health and in disease. Several members of the group are studying the part of the brain called the amygdala, which plays a key role in the fear response, memory storage and pleasure. There are two amygdalae in the human brain that are almond shaped clusters of nervous tissue that sit deep inside the temporal lobe. The temporal lobes are the regions of the brain just beneath the skull closest to the ears.

A technical approach used by many of the researchers in the Role and Talmage lab is a relatively new research technique called optogenetics, which allows scientists to activate a select and specific group of neurons with light. Optogenetics involves the insertion of a virus into neurons to make the neurons light responsiveness.

A common interest of the laboratory is in the neurotransmitter acetylcholine and the networks of cholinergic neurons that synthesize and release this transmitter. These networks are essential for us to be able to pay attention and to remember who we know and love and what circumstances frighten us. If the cholinergic network of communication is disrupted, then one of the many functions of the brain that can go awry is memory such as in Alzheimer’s disease.

Jone works on Talmage side of the Role and Talmage lab. Talmage studies a specific protein that is responsible for the development of the nervous system called Neuregulin-1. This protein also plays a significant role in schizophrenia. Talmage explained that the work they do in this lab can lead to the development of treatments for the disease.

Jone and her colleagues have weekly meetings with Role and Talmage, or “Rolemage,” where they discuss their findings and open the floor for discussion and suggestions. During these meetings, the latest research results are presented including fluorescently dyed green and red neurons and plots of neuronal activity. One week, Dr. Gretchen Lopez-Hernandez presented her research on the basolateral amygdala and the nucleus basalis—both structures of the brain. To an outsider, these words used sound like an entirely different language, which leads to another challenge for the researchers.

Neurological and psychiatric diseases are important and devastating illnesses, and the research neuroscientists are trying to do needs financial support.

“We haven’t been good advocates for ourselves,” said Role. “We need to learn better how to communicate why this work is exciting and important.”

“It is very powerful to move the forefront of medicine,” Ballinger said. “Why does anyone do anything else? The brain is who we are, and it is what we are.”

 

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