Farley Sean J, Radley Jason J, Freeman John H
Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa 52242.
Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa 52242
J Neurosci. 2016 Feb 17;36(7):2190-201. doi: 10.1523/JNEUROSCI.3361-15.2016.
Previous studies showed that amygdala lesions or inactivation slow the acquisition rate of cerebellum-dependent eyeblink conditioning, a type of associative motor learning. The current study was designed to determine the behavioral nature of amygdala-cerebellum interactions, to identify the neural pathways underlying amygdala-cerebellum interactions, and to examine how the amygdala influences cerebellar learning mechanisms in rats. Pharmacological inactivation of the central amygdala (CeA) severely impaired acquisition and retention of eyeblink conditioning, indicating that the amygdala continues to interact with the cerebellum after conditioning is consolidated (Experiment 1). CeA inactivation also substantially reduced stimulus-evoked and learning-related neuronal activity in the cerebellar anterior interpositus nucleus during acquisition and retention of eyeblink conditioning (Experiment 2). A very small proportion of cerebellar neurons responded to the conditioned stimulus (CS) during CeA inactivation. Finally, retrograde and anterograde tracing experiments identified the basilar pontine nucleus at the confluence of outputs from CeA that may support amygdala modulation of CS input to the cerebellum (Experiment 3). Together, these results highlight a role for the CeA in the gating of CS-related input to the cerebellum during motor learning that is maintained even after the conditioned response is well learned.
The current study is the first to demonstrate that the amygdala modulates sensory-evoked and learning-related neuronal activity within the cerebellum during acquisition and retention of associative learning. The findings suggest a model of amygdala-cerebellum interactions in which the amygdala gates conditioned stimulus inputs to the cerebellum through a direct projection from the medial central nucleus to the basilar pontine nucleus. Amygdala gating of sensory input to the cerebellum may be an attention-like mechanism that facilitates cerebellar learning. In contrast to previous theories of amygdala-cerebellum interactions, the sensory gating hypothesis posits that the gating mechanism continues to be necessary for retrieval of cerebellar memory after learning is well established.
先前的研究表明,杏仁核损伤或失活会减缓小脑依赖性眨眼条件反射的习得速度,这是一种联合运动学习类型。本研究旨在确定杏仁核与小脑相互作用的行为本质,识别杏仁核与小脑相互作用的神经通路,并研究杏仁核如何影响大鼠的小脑学习机制。中央杏仁核(CeA)的药理学失活严重损害了眨眼条件反射的习得和保持,表明在条件反射巩固后杏仁核仍继续与小脑相互作用(实验1)。在眨眼条件反射的习得和保持过程中,CeA失活还显著降低了小脑前间位核中刺激诱发的和与学习相关的神经元活动(实验2)。在CeA失活期间,只有极小比例的小脑神经元对条件刺激(CS)有反应。最后,逆行和顺行示踪实验确定了CeA输出汇合处的基底桥核,它可能支持杏仁核对小脑CS输入的调节(实验3)。总之,这些结果突出了CeA在运动学习过程中对小脑CS相关输入的门控作用,即使在条件反应已熟练习得后该作用仍持续存在。
本研究首次证明,在联合学习的习得和保持过程中,杏仁核对小脑中感觉诱发的和与学习相关的神经元活动具有调节作用。这些发现提出了一种杏仁核与小脑相互作用的模型,其中杏仁核通过从内侧中央核到基底桥核的直接投射来门控小脑的条件刺激输入。杏仁核对小脑感觉输入的门控可能是一种类似注意力的机制,有助于小脑学习。与先前关于杏仁核与小脑相互作用的理论不同,感觉门控假说认为,在学习充分建立后,门控机制对于小脑记忆的提取仍然是必要的。