Medina Javier F, Nores William L, Mauk Michael D
W. M. Keck Center for the Neurobiology of Learning and Memory, University of Texas Medical School, Houston 77030, USA.
Nature. 2002 Mar 21;416(6878):330-3. doi: 10.1038/416330a.
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 movements. Data from several forms of motor learning provide support for this tenet. 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 fibres. Climbing fibre activity elicited by an unconditioned stimulus is inhibited during the expression of conditioned responses-consistent with the inhibitory projection from the cerebellum to inferior olive. 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 system, suggest that transient inhibition of climbing fibres below their background level is the signal that drives extinction.
小脑学习理论的一个基本信条认为，来自下橄榄核的攀爬纤维传入提供了一个教学信号，促进运动的逐渐适应。多种形式的运动学习数据支持了这一信条。例如，在经典条件反射性眼睑条件反射中，当一个音调反复与强化的非条件刺激（如眶周刺激）配对时，非条件刺激通过激活攀爬纤维促进条件性眼睑反应的习得。在条件反应的表达过程中，非条件刺激引发的攀爬纤维活动受到抑制，这与小脑向下橄榄核的抑制性投射一致。在这里，我们表明，攀爬纤维的抑制作为消退的教学信号，即在不给予非条件刺激的情况下呈现音调时，学习不做出反应。我们使用可逆性注入突触受体拮抗剂来表明，阻断对攀爬纤维的抑制性输入会阻止条件反应的消退，而阻断兴奋性输入则会诱导消退。这些结果，结合在小脑 - 橄榄核系统计算机模拟中对攀爬纤维活动的分析，表明攀爬纤维在其背景水平以下的短暂抑制是驱动消退的信号。
