Inhibitory Cerebello-Olivary Projections and Blocking Effect in Classical Conditioning

The inferior olive is a structure that sends information to the cerebellum concerning unconditioned stimuli. According to the researchers, the inferior olive is functionally inhibited by the cerebellum during conditioning via a negative feedback mechanism.

L. J. Kamin discovered in 1968 that when a conditioned stimulus (CS) ""A"" was extensively paired to an unconditioned stimulus (US) (A-US), and then another conditioned stimulus "B" was compounded with A and the same US (AB-US), almost no conditioning happened to B. He did note, however, that if A was previously unconditioned (or only weakly) with the US, then B (together with A) gains tremendous strength as compound conditioning occurs.  The necessary neural circuitry involved in classical conditioning of eyeblink and nictitating membrane response in rabbits is well understood and is, therefore, essential in studying the phenomenon of blocking at the level of the neuron. Eyeblink conditioning is elicited when a CS (tones or lights) is paired with a US (air puffs). The unconditioned response, in this case, is eyelid closure.

The inferior olive ‘reinforces’ US input to the cerebellum (supports eyeblink conditioning). In rabbit models, neurons in the inferior olive show increased neural activity to the air puff US as well as periorbital stimulation US during the early stage of CS-US training. The same is not observed when animals perform CRs during CS-US trials. Examination of the complex spike response of Purkinje fibers in the cerebellum indicates that the inferior olive’s capacity to relay US information to the cerebellum becomes functionally suppressed.

Projections from the cerebellum to the inferior olive that contain GABA (gamma-aminobutyric acid) mediate the negative feedback mechanism. They regulate the inferior olive's activity thereby blocking the eyeblink conditioning activity. Infusing picrotoxin (PTX), a GABA antagonist, into the olives of well-trained rabbits enables Purkinje cells to respond to the US. The animals continue to perform CRs proving that GABA mediates the CR-induced inhibition of the inferior olive activity.

In another experiment with two phases, Kamin subjected rabbits to seven daily sessions of tone-air puff in the first step. In the second phase, he subjected the animals to five sessions of tone-light-air puff compound conditioning with either PTX or artificial cerebrospinal fluid being administered directly into the inferior olive. Animals used as controls experienced only the second phase of conditioning. Later, the animals were subjected to light-air puff stimuli to assess if conditioning to light had happened during compound conditioning. The control and PTX rabbits expressed meaningful learning to the light CS compared with the ACSF models. ACSF animals exhibited blocking (conditioning to light was not evident).

It’s possible that PTX infusion into the inferior olive during compound tone-light-air puff conditioning hindered tone-induced cerebellar inhibitions of US-evoked inferior olive responses. There was no blocking. For the controls that never received tone-air puff training in advance, conditioning to the light stimulus accrued during compound training since no cerebellar inhibition of the inferior olive activity in response to incoming US information.

From the information above, it suffices to say that cerebello-olivary projection that contains GABA plays a fundamental responsibility in mediating blocking in eyeblink conditioning. This projection can be used in humans to train them so as to acquire some desired behavior. Scientists use animal models such as monkeys and rats in such experiments like the one above and much more in medical research (for example, gene mutations). Once completely understood, the results can then be reproduced in human beings to treat certain conditions and to understand the pathophysiology of some of these diseases.

Work Cited

Kamin, Leon J. "Attention-Like’ Processes in Classical Conditioning." In Miami Symposium on the Prediction of Behavior: Aversive Stimulation. University of Miami Press, 1968.