Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses

Javier F. Medina, William L. Nores and Michael D. Mauk ()
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Javier F. Medina: W. M. Keck Center for the Neurobiology of Learning and Memory, University of Texas Medical School
William L. Nores: W. M. Keck Center for the Neurobiology of Learning and Memory, University of Texas Medical School
Michael D. Mauk: W. M. Keck Center for the Neurobiology of Learning and Memory, University of Texas Medical School

Nature, 2002, vol. 416, issue 6878, 330-333

Abstract: Abstract A fundamental tenet of cerebellar learning theories asserts that climbing fibre afferents from the inferior olive provide a teaching signal that promotes the gradual adaptation of movements1,2,3. Data from several forms of motor learning provide support for this tenet4,5,6,7,8. In pavlovian eyelid conditioning, for example, where a tone is repeatedly paired with a reinforcing unconditioned stimulus like periorbital stimulation, the unconditioned stimulus promotes acquisition of conditioned eyelid responses by activating climbing fibres9,10,11,12. Climbing fibre activity elicited by an unconditioned stimulus is inhibited during the expression of conditioned responses9,10,11—consistent with the inhibitory projection from the cerebellum to inferior olive6,13. Here, we show that inhibition of climbing fibres serves as a teaching signal for extinction, where learning not to respond is signalled by presenting a tone without the unconditioned stimulus. We used reversible infusion of synaptic receptor antagonists to show that blocking inhibitory input to the climbing fibres prevents extinction of the conditioned response, whereas blocking excitatory input induces extinction. These results, combined with analysis of climbing fibre activity in a computer simulation of the cerebellar–olivary system14,15,16, suggest that transient inhibition of climbing fibres below their background level is the signal that drives extinction.

Date: 2002
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DOI: 10.1038/416330a

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