Progressive movement disorders, such as Parkinson's disease and Huntington's disease, are devastating for millions of Americans. Scientists, neurologists and other physicians are actively engaged in research to try to better understand how the brain works and what happens when things go wrong.
Using Pavlov's conditioning to understand the brain
A team of researchers at UCLA recently discovered more about how a certain cluster of cells in the brain works and how they may influence abnormal behaviors common in nervous-system disorders. Their research was recently published in the journal Neuron. Studies in postmortem brain tissue have found that a subset of cells in a part of the brain called the striatum are disrupted in Tourette's syndrome and Huntington's disease. Sotiris Masmanidis, PhD , and his team further studied these cells in mice by using a modern form of Russian scientist Ivan Pavlov's famous experiment. Pavlov would ring a bell each time he fed his dogs. The dogs eventually drooled in anticipation when they heard the bell, even before food appeared.
"Based on our work and that of several other groups, we think these cells have a broader implication in understanding a wide range of neurological diseases," says Dr. Masmanidis, an assistant professor of neurobiology at the David Geffen School of Medicine at UCLA. "The Pavlovian response is the building block of associative behavior, things like learning to walk or ride a bike. Once we do something beneficial, it is stamped on our brain, and we are encouraged to do it again."
In the UCLA research, scientists used unfamiliar smells followed by a drop of condensed milk. Eventually, the mice began licking at the air in anticipation when exposed to the smell. Using specialized electrodes and optogenetics, or using light to control cells, the researchers switched off the cells that support the neurons in the striatum.
Dr. Sotiris Masmanidis
What they found was that when those cells are turned off, the mice lick at the air in anticipation 50 percent less frequently. This led the researchers to conclude that malfunctions in these cells may be responsible for a range of nervous-system disorders, including Huntington's, Tourette's and Parkinson's. Being able to isolate the function of responsible cells may lead to better treatments down the road that selectively target these cells or help prevent their degradation.
Next steps
"We know some basic features of movement disorders like Parkinson's, but we don't know exactly what goes awry in the patterns of brain activity to generate the aberrant behavior," Dr. Masmanidis says. "By studying one type of brain cell at a time and how turning that type of cell on or off alters the activity of downstream cells, we can carefully dissect out the contribution of specific cells to behavior and make more detailed links to potential diseases."
Upcoming doctors and neuroscientists have a lot of space to learn and advance the field, possibly bringing new treatments onto the scene. Dr. Masmanidis says that new technologies are revolutionizing the field of neuroscience with new ways to record and manipulate brain activity with unprecedented precision.
There's a notion that there are about as many neurons in the human brain as there are galaxies in the universe and that we may understand even less about the mechanics of circuits in the brain than we do about the mechanics of galaxies.
"I think the next few decades will see an explosion of new knowledge for how the brain works normally and how the brain works in diseases," he says. "It's a huge opportunity for budding scientists and clinicians."
By Patricia Chaney
