Unlocking the mysteries of learning and memory

Thursday, April 20, 2006

The human brain is the ultimate learning machine. In the blink of an eye, the great mass of ten billion neurons can learn a new word, memorize a phone number, and recall vivid memories from childhood based on a simple smell. But how the brain accomplishes these feats remains one of life’s greatest mysteries. Dr. Dan Johnston, professor of neurobiology, aims to solve this big mystery by understanding how learning and memory works at the most basic level—in the single neuron cell.

Dr. Dan Johnston, director of the Center for Learning and Memory. Photo: Matt Lankes

“I’ve always been interested in how neurons process and store information,” says Johnston, director of the college’s Center for Learning and Memory and the Institute for Neuroscience.

Johnston works on neurons in the hippocampus, an important region of the brain for learning and short-term memory. “The hippocampus is a fast learner,” he describes. “It takes in information from everyday activities, holds it temporarily, gets rid of what isn’t important, and helps slowly develop a long-term memory where appropriate.” Without a hippocampus, you wouldn’t be able to learn or remember any new information.

The hippocampus is also one of the first regions of the brain to suffer from Alzheimer’s disease and is prone to epileptic seizures. “It turns out that the things that make the hippocampus a fast learner—the circuitry and the connections—also make it the most prone area of the brain to have seizures,” says Johnston.

Learning Changes Neurons
When learning occurs, neurons in the hippocampus change, and much attention has focused on how learning changes synapses—the contact points where neurons connect. Synapses connect the axon end of one neuron to the dendrites of another. During learning, synapses go through molecular and physical changes that help information flow more easily between affected neurons, like widening a bridge allows more cars to travel across.

“When learning and memory events occur, changes in synapses increase the throughput [of information through] learned synapses,” explains Johnston. But synapses aren’t the only parts of a neuron affected by learning and memory.

Johnston and his colleagues are finding that learning changes neurons throughout their dendrites—the long, branchlike extensions of these cells. “Originally we thought that dendrites were passive and that only synapses changed during learning,” says Johnston. “Our work strongly supports the idea that learning involves changes in dendrites.”

In a recent article published in Nature Neuroscience, Johnston showed that a kind of membrane channel, called an h-channel, increased in dendrites of rat hippocampal cells when they were exposed to a simulated learning task. He and his colleagues electrically stimulated neurons in a pattern that mimics the electrical pulses that occur during learning. They found that the neurons’ dendrites produced more h-channels and rapidly produced proteins used to build more h-channels.

h-channels may keep neurons from over-firing when information is pouring into them from many synapses, says Johnston. A neuron’s dendrites serve as a kind of information switchboard, and a single hippocampal neuron can be connected to thousands of other neurons through synapses on its dendrites.

During learning, Johnston says the production of new h-channels in dendrites could help a neuron stay in normal firing range. “h-channel plasticity might keep the cell within an operating window in which it can continue to learn,” he says.

In a separate study published in Neuron, Johnston found that rats with low numbers of h-channels in their dendrites experienced epileptic seizures. “We found that a decrease in h-channels allowed cells to be hyper-excited,” he explains. “When there are no h-channels, the cells fire more and this leads to epilepsy.” It’s not clear yet what mechanisms cause h-channels to decrease in dendrites, but Johnston and his colleagues did find that changes in other channels can be acquired through some injury to the brain, a process they reported in Science that they labeled “acquired channelopathy.”

The relationship between disease and learning and memory comes as no surprise to Johnston, who says that the fundamental mechanisms of learning and memory overlap in almost all areas of neuroscience. “You start talking about schizophrenia, age-related memory problems, or mental health disorders,” he says, “and you start talking about the basic mechanisms of learning and memory: synaptic transmission and the plasticity and circuitry of neurons.”

Epicenter for Learning and Memory
To better understand the basic mechanisms of learning and memory, Johnston is bringing together top minds from diverse fields at the college’s new Center for Learning and Memory (CLM). Scientists from chemistry and psychology to medicine and computer science will find a home at the CLM, which promises to be at the epicenter of new discoveries in learning and memory.

The CLM will provide a wealth of research opportunities for undergraduate and graduate students, eventually housing a total of twelve research faculty in the recently completed Neural and Molecular Science building.

Already joining the CLM is Dr. Helmut Koester, an innovator in the development of high-speed optical imaging of neurons, a method that allows him to view activity around a single synapse. Dr. Rick Aldrich, a renowned neuroscientist who studies the molecular mechanisms of ion channel function, will be joining the CLM and the Department of Neurobiology from Stanford University in Spring 2006.

“This is going to be an exciting place for doing neuroscience,” Johnston says.