Scientists have tried for decades to determine what triggers epileptic seizures, the central nervous system disorder whose symptoms range from mild disorientation to severe convulsion. The National Institutes of Health estimates that epilepsy currently affects more than 2 million Americans. Many of these people’s lives are severely restricted because they live in fear that seizures will strike without warning, according to Pierre-Olivier Polack, an assistant professor at the Center for Molecular and Behavioral Neuroscience (CMBN) at Rutgers University-Newark,
“As seizures are unpredictable, epileptic patients are usually not allowed to drive. Most of them can’t work,” Polack explains, “because they can become a danger for themselves and for others during seizures. They need to take medication all the time.” And for many patients, each seizure compounds existing damage within the brain, making additional seizures more likely.
One of Polack’s primary research goals is to unravel the many mysteries of epilepsy. His lab at CMBN is one of just a handful of facilities in the world equipped to investigate epilepsy and other brain phenomena with unprecedented precision – by recording in real time the activity of neurons within the brains of awake, fully functioning mice. This monitoring, through which Polack hopes to gain valuable insight into human epilepsy, is possible because of a genetic engineering technique less than a decade old that adds a fluorescent protein to neurons within the brain – producing observable light when neurons are active while leaving brain function completely unaffected.
“We can image the activity of hundreds of neurons at the same time. We can see them flashing when they are active,” says Polack, who considers this technique a great step forward from tools that investigators previously used.
“In the past, one of the problems scientists had studying epilepsy was that they could only work either in vitro or with anesthetized animals,” he says. “By definition there can be no spontaneous epileptic activity in tissue in vitro, and animals are kept anesthetized by chemicals that modify the way the brain works. That makes interpretation of any observed brain activity unreliable.”
Polack hopes that fluorescent protein technology will now permit him to track seizures with high accuracy – from start to finish, neuron by neuron.
In addition to investigating how neuronal networks generate epileptic seizures, Polack is interested in how the brain encodes visual information, and how the behavioral context changes visual perception. This area of study may have applications to multiple disorders including autism, schizophrenia, and Alzheimer’s.
Polack’s focus is on neurons in the visual cortex, the part of the brain that processes nerve impulses triggered by light that enters the eyes. He has found that information passing through those neurons actually originates in numerous regions of the brain and relates to processes that go far beyond eyesight. “We know that emotion, working memory, attention, and sleep vs. wakefulness all can alter the way you process visual information,” Polack says, “and we are using these properties of the brain to understand, at the cellular level, how these influences change the way neurons compute visual stimuli.”
Locomotion might be the most important variable of all, and Polack has designed his lab to capture its effect on how neurons perform. One device Polack uses is a spherical treadmill, a large Styrofoam ball on which the animal has substantial freedom to run in any direction it chooses, but at the same time remains in place so that Polack and his team can accurately monitor the neuronal activity, eye position and other behavioral parameters.
Polack has found how when a mouse is running, there is an increase in the amount of visual information that streams through in the animal’s visual cortex – in a sense, bigger bandwidth. “During locomotion you need to be more on top of changes that are occurring in your visual field,” he explains. “While you’re resting, there is much less movement, and so you need less information to be able to really understand what is going on around you.”
The two aspects of Polack’s research are complementary. There is an unknown line between a brain that is performing normally and one having an epileptic seizure. The more he can learn about how neuronal networks function, the better sense Polack thinks he will have of where that line might be, what causes the brain to cross that line, and what can be done to prevent it from happening.
“During epileptic seizures, the activity of neurons is abnormally synchronized. We need to know how neurons synchronize to find out how to prevent them from synchronizing or find a strategy to prevent epileptic neurons from contaminating the others with their abnormal activity.”
Pierre-Olivier Polack was born in France and studied veterinary medicine at the École Nationale Vétérinaire de Nantes, where he discovered that the area of animal anatomy that fascinated him the most – the brain – was seldom, if ever, what veterinarians find themselves either treating or researching.
After he met Stephane Charpier, a scientist at the College de France who was placing electrodes inside of neurons to study how these cells initiate and propagate epileptic seizures – something he had not known was possible – his interest in veterinary practice waned and he decided to study neuroscience, in which he earned a doctorate at the Université Pierre et Marie Curie (Paris 6). After completing postdoctoral fellowships – with Diego Contreras at the University of Pennsylvania and Peyman Golshani at UCLA – Polack came to CMBN as an assistant professor in 2014.
“Rutgers gives me the means to do great science,” says Polack. “It’s the best environment you can imagine. It’s amazing how what I want to do fits with the interests of so many researchers who are working here. To do great research, you need interactions with people whose research and techniques are complementary to yours. People here instantly give you great ideas.”