Yale Scientist Identifies Key Brain Structure that Blocks Learning In Some Cases of Pavlovian Conditioning

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. The famous experiments provided a useful tool for discovering a great deal more about how animals – and humans – learn from their environment.

Now scientists from Yale University and the University of Southern California have found a neurological explanation for a phenomenon called blocking, which occurs after a conditioned reflex is learned and prevents animals from becoming conditioned simultaneously to a new stimulus, such as a flashing light.

A key brain structure called the inferior olive is involved in this blocking phenomenon, according to research by Yale neuroscientist Jeansok J. Kim and his USC colleague Richard F. Thompson. Their research, which was conducted with USC post-doctoral fellow David J. Krupa, was published in the Jan. 23 issue of the journal Science.

A good evolutionary reason exists for having a blocking mechanism to avoid being confused by new stimuli that overlap with previously learned associations, Kim said. 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.

“In order to adapt to its environment, an animal must respond selectively to stimuli that reliably predict biologically significant events, such as food availability. 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,” explained Kim, an assistant professor of psychology at Yale.

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.

Instead of the dogs used by Pavlov, the researchers used 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 tone or light causes the rabbit to blink, even without the puff of air. This conditioned reflex in rabbits was first described by Yale psychologist Allan J. Wagner, a pioneer in animal learning.

Years of experimentation, including work in Thompson’s laboratory, established 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 cells called 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 now been given strong support by the experiment carried out by Kim, formerly a post-doctoral researcher at USC, and his colleagues. By surgically implanting a microsyringe in the olive to inject a specific chemical antagonist known to block the action of GABA, the researchers were able to selectively turn off the process of information feedback between the cerebellum and olive in living animals.

The results were simple and dramatic – animals in which the GABA connection to the olive had been chemically severed showed no blocking effect.

In the experiments, 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 flash of light was added to the tone-air puff pairing. Half the rabbits received this second training while having the GABA antagonist present in the cerebellar connections to the olive; the other half received neutral, control injections of artificial cerebrospinal fluid (ACSF). 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.

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