Only a few millimeters divide the areas in the human brain that two Rutgers neuroscientists—Tracey J. Shors and Laszlo Zaborszky—analyze in their separate research pursuits. But they might as well be worlds apart. She investigates how to prevent dementia; he researches treating it.
From her lab in New Brunswick, Shors, a professor in the Department of Psychology as well as the Center for Collaborative Neuroscience at Rutgers–New Brunswick, is working on the welcome news that new neurons are born throughout adult life, their success linked to rigorous learning. Zaborszky, a professor in the Center for Molecular and Behavioral Neuroscience at Rutgers–Newark, is pinpointing the locations and neural connections of so-called cholinergic cells, whose decay is considered a factor in the onset of Alzheimer’s disease.
A fraction of space separates these zones of rebirth and loss. Whether the two researchers can bridge that space to form a broader picture of what goes on in our heads is encouraging. But both are nonplussed. It is all part of the challenge, they say, of exploring the world’s most complex object.
“Neuroscience is a relatively young science,” says Zaborszky. “The idea is that you want to understand a complex problem. And because the brain is more complicated than anything else, you need other experts—even in your own narrow field.”
It was only in the late 1990s that neuroscientists proved that new neural cells grow in the adult hippocampus region through a process called neurogenesis. Shors’s work has advanced the connection between this growth and individual learning. But there is a catch.
“Even though these new cells are made every single day, they can die,” she says. “We showed that they survive, that they are ‘rescued,’ only if the individual learns something new. But learning itself must occur, and it should be with some effort.
“People tend to think of learning as something you do at the library or in class, but the brain is always learning,” she goes on. “It is nonetheless difficult to keep challenging yourself. Most people, as they get older, tend to gravitate toward things they already know how to do. It is difficult to think about how to challenge yourself.”
One recent development is the connection between rescued cells and exercise, which likely stems from early humans having to be vigorously active in their struggle to survive. The brain is extremely dynamic, or “plastic,” says Shors. Its functional development responds to our environment, what we do with ourselves. The extent of this plasticity is only just beginning to be appreciated.
For his part, Zaborszky addresses the “scaffolding” of the cholinergic cells, identifying their neuroanatomy so that pharmacology experts might one day design drugs that target the area and combat their loss.
“There are many other neurons that degenerate in Alzheimer’s, but this is one of the most-known systems,” says Zaborszky. “The axonal processes of cholinergic neurons provide acetylcholine, which is essential to their normal functioning. Some of the disease symptoms indeed can be explained by the loss of these cholinergic neurons. We started very early to first understand their circuitry. You want to understand the anatomy. Then comes everything else.”
He spent last summer with colleagues in Germany piecing together a 3-D map of this region of the brain, its clusters of cholinergic cells and the receptors on the surface of these neurons superimposed so that scientists can figure out the interrelations. Connections are usually defined by location, says Zaborszky, but how that relates to function is something of a mystery.
One goal is early identification of the cells vulnerable to decay so that treatments can be designed decades before Alzheimer’s manifests itself. In most individuals, the disease progresses for 15 or 20 years before it becomes evident and irreversible decline has set in.
“Before the majority of cholinergic cells are lost, we might be able to stimulate pharmacologically through their receptors or through deep-brain stimulation of the remaining cells,” he says. “But these treatment strategies have yet to be realized. The major effort is to have early diagnoses, but it’s hard to select people when there are only minimal cognitive symptoms early on.”
So is brain health simply a matter of exercising and working on difficult mathematical problems? Not surprisingly, says Shors, the answer is complicated.
“It’s compelling to think that if you’re more active and more mentally and physically engaged in your life that you’ll be less likely to have dementia. But it’s been really difficult to prove that,” she says. “My feeling is that it certainly can’t hurt. For all sorts of reasons.”
— Wendy Plump