Nearly 100 years ago, the Russian physiologist Ivan Petrovich Pavlov trained dogs to associate the ringing of a bell with being fed. Eventually, the dogs would salivate at the sound of the bell, even when food was not presented, a response Pavlov called conditioned reflex. These experiments provided scientists with a useful tool for learning about how animals -- and humans -- learn from their environment.
Decades later, researchers discovered that animals which are conditioned to have a specific reaction to one stimulus, such as a bell, cannot then also be conditioned to have the same reaction to a different stimulus, such as a flashing light. They called this phenomenon "blocking."
Inferior olive is key. Scientists from Yale and the University of Southern California (USC) have now found that the blocking phenomenon is linked to a key brain structure called the inferior olive. The research -- conducted by Jeansok J. Kim, assistant professor of psychology, and his USC colleagues Professor Richard F. Thompson and postdoctoral fellow David J. Krupa -- was published in the Jan. 23 issue of the journal Science.
There is a good evolutionary reason for having a blocking mechanism that prevents new stimuli from overlapping with previously learned associations, says Kim. Blocking is believed to regulate the process by which animals and humans learn from their environment by preventing them from being distracted by irrelevant signals, he explains.
"In order to adapt to its environment, an animal must respond selectively to stimuli that reliably predict biologically significant events, such as food availability," he says. "In the interest of efficiency and simplicity, animals must avoid forming associations with other stimuli that provide no new information. Blocking appears to circumvent such redundant learning."
While blocking was first reported in 1968, Kim and his colleagues are the first to pinpoint the area of the brain where the phenomenon occurs and to confirm that information feedback between the cerebellum and the inferior olive is the mechanism.
The scientists began by studying the process of associative learning. Instead of using dogs as Pavlov did, the researchers employed a now-standard conditioning regime in which rabbits learn to associate an external stimulus -- a tone or light -- with a puff of air on an eye. After training, the rabbits blink in reaction to the tone or light, even without the puff of air. This conditioned reflex in rabbits was first described by Allan J. Wagner, a pioneer in animal learning who holds the James Rowland Angell Professorship at Yale..
The scientists first determined that this kind of associative learning takes place in the cerebellum (the finely convoluted, round structure at the back of the brain) and specifically involves the Purkinje cells. A brainstem structure called the inferior olive (named because of its shape) connects to the Purkinje cells. These links are thought to carry sensory information to the cerebellum.
The olive also is reciprocally linked to the cerebellum by nerve cells that, when active, release a specific chemical called GABA. Neuroscientists have theorized that these connections could carry an inhibitory message to the olive that blocks new associations once learning has taken place.
This theory has been supported by the experiment carried out by Kim, formerly a postdoctoral researcher at USC, and his colleagues. By surgically implanting a microsyringe in the olive to inject a specific chemical that blocks the action of GABA, the researchers were able to selectively turn off the process of information feedback between the cerebellum and olive in animals.
In the experiment, animals were first trained to associate a puff of air with a tone. After the rabbits learned to blink whenever they heard the tone, a second stimulus -- a flash of light -- was added. Half the rabbits who received this second training were given a GABA-blocker to sever the cerebellar connections to the olive; the other half received control injections of artificial cerebrospinal fluid (ACSF), a neutral substance. Then, a separate group of rabbits that had never received tone training was trained simultaneously with tone and pulses of light, which produced conditioned reflexes to both stimuli.
The control group receiving only ACSF injections showed classic blocking behavior -- they did not learn to associate the light with the puff of air. Those injected with the GABA blocker made the association just as frequently as animals in the group conditioned simultaneously to tone and light.
This research was supported by grants from the National Institute on Aging, the National Science Foundation, the Office of Naval Research and the Sankyo Co.