Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses
Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses
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DOI：
10.1038/416330a
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发表时间：
2002-03-21
期刊：
影响因子：
64.8
通讯作者：
Mauk, MD
中科院分区：
文献类型：
--
作者：
Medina, JF;Nores, WL;Mauk, MD
小脑学习理论的基本原则认为，来自下橄榄的攀爬纤维传入提供了促进运动逐渐适应的教学信号(1-3)。来自多种运动学习形式的数据为这一原则提供了支持(4-8)。例如，在巴甫洛夫眼睑调节中，当音调与眶周刺激等增强的无条件刺激重复配对时，无条件刺激通过激活攀爬纤维来促进获得条件性眼睑反应(9-12)。由非条件刺激引起的攀爬纤维活动在条件反应表达期间受到抑制(9-11) - 与从小脑到下橄榄的抑制投射一致(6,13)。在这里，我们表明，攀爬纤维的抑制可以作为灭绝的教学信号，其中通过在没有无条件刺激的情况下呈现音调来表示学会不做出反应。我们使用突触受体拮抗剂的可逆输注来表明，阻断攀爬纤维的抑制性输入可以防止条件反应的消退，而阻断兴奋性输入则会诱导消退。这些结果与小脑-橄榄系统计算机模拟中攀爬纤维活动的分析相结合(14-16)，表明攀爬纤维低于其背景水平的短暂抑制是驱动灭绝的信号。
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(1-3). Data from several forms of motor learning provide support for this tenet(4-8). 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 fibres(9-12). Climbing fibre activity elicited by an unconditioned stimulus is inhibited during the expression of conditioned responses(9-11)-consistent with the inhibitory projection from the cerebellum to inferior olive(6,13). 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 system(14-16), suggest that transient inhibition of climbing fibres below their background level is the signal that drives extinction.