Connecting the Dots of the Cerebro-Cerebellar Role in Cognitive Function: Neuronal Pathways for Cerebellar Modulation of Dopamine Release in the Prefrontal Cortex
Connecting the Dots of the Cerebro-Cerebellar Role in Cognitive Function: Neuronal Pathways for Cerebellar Modulation of Dopamine Release in the Prefrontal Cortex
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DOI：
10.1002/syn.20960
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发表时间：
2011-11-01
期刊：
影响因子：
2.3
通讯作者：
Blaha, Charles D.
中科院分区：
文献类型：
--
作者：
Rogers, Tiffany D.;Dickson, Price E.;Blaha, Charles D.
自闭症、精神分裂症和其他认知障碍的小脑受累通常与前额叶皮质病理学有关。然而，潜在的神经机制在很大程度上是未知的。此前在小鼠身上已经证明，刺激小脑齿状核（DN）会引起内侧前额叶皮质（mPFC）中多巴胺（DA）的释放。在这里，我们研究了小脑调节mPFC DA释放的神经元回路。固定电位安培法被用来确定两个候选途径的贡献，小脑可能会调节mPFC DA的释放。在乌拉坦麻醉的小鼠中，将局部麻醉剂利多卡因（0.02 μ g）或离子型谷氨酸受体拮抗剂犬尿氨酸（0.5 μ g）注入丘脑背内侧核或腹外侧核（ThN md; ThN vl）或腹侧被盖区（VTA）后，记录了DN刺激（50 Hz）诱发的mPFC中DA释放。在VTA内输注利多卡因或犬尿酸盐后，DA释放降低了50%。在ThN md和ThN vl内输注任一种药物后，DA释放分别降低了类似于35%和15%。利多卡因或犬尿氨酸输注后DA释放的减少没有显着差异，表明VTA和ThN中的神经元细胞主要（如果不是完全）被多巴胺能输入激活。本研究表明，在自闭症，精神分裂症和其他认知障碍中常见的小脑神经病理学变化可能会导致小脑mPFC电路的功能丧失，表现为mPFC中的异常多巴胺能活性。此外，这些结果特别暗示谷氨酸作为mPFC多巴胺能活性的调节剂。Synapse 65：1204-1212，2011. (C)2011 Wiley-Liss，Inc.
Cerebellar involvement in autism, schizophrenia, and other cognitive disorders is typically associated with prefrontal cortical pathology. However, the underlying neuronal mechanisms are largely unknown. It has previously been shown in mice that stimulation of the dentate nucleus (DN) of the cerebellum evokes dopamine (DA) release in the medial prefrontal cortex (mPFC). Here, we investigated the neuronal circuitry by which the cerebellum modulates mPFC DA release. Fixed potential amperometry was used to determine the contribution of two candidate pathways by which the cerebellum may modulate mPFC DA release. In urethane anesthetized mice, DA release evoked by DN stimulation (50 Hz) was recorded in mPFC following local anesthetic lidocaine (0.02 mu g) or ionotropic glutamate receptor antagonist kynurenate (0.5 mu g) infusions into the mediodorsal or ventrolateral thalamic nucleus (ThN md; ThN vl), or the ventral tegmental area (VTA). Following intra-VTA lidocaine or kynurenate infusions, DA release was decreased by similar to 50%. Following intra-ThN md and ThN vl infusions of either drug, DA release was decreased by similar to 35% and 15%, respectively. Reductions in DA release following lidocaine or kynurenate infusions were not significantly different indicating that neuronal cells in the VTA and ThN were activated primarily if not entirely by glutamatergic inputs. The present study suggests that neuropathological changes in the cerebellum commonly observed in autism, schizophrenia, and other cognitive disorders could result in a loss of functionality of cerebellar-mPFC circuitry that is manifested as aberrant dopaminergic activity in the mPFC. Additionally, these results specifically implicate glutamate as a modulator of mPFC dopaminergic activity. Synapse 65:1204-1212, 2011. (C) 2011 Wiley-Liss, Inc.