Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.
Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.
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DOI：
10.1002/syn.20525
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发表时间：
2008-07
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：
Mittleman, Guy;Goldowitz, Daniel;Heck, Detlef H.;Blaha, Charles D.
小脑和额叶皮质病变在精神分裂症、自闭症和其他发育障碍中经常被报道。前额叶和小脑病变之间是否存在关系尚不清楚。采用固定电位安培法，记录了50 Hz、200 μA的氨基甲酸乙酯麻醉的鼠脑（Lc/+）和野生型（+/+）小鼠小脑浦肯野细胞100%丢失的前额叶皮层多巴胺（DA）外排。25脉冲和100脉冲的小脑刺激分别在刺激后持续12 s和25 s，引起+/+小鼠前额叶皮层DA外排。相比之下，25脉冲小脑刺激在Lc/+小鼠中未能引起前额叶皮层DA外排，这表明依赖于小脑浦肯野细胞输出。与类似的小脑刺激相比，齿状核刺激（25个脉冲）引起的前额皮质DA外排增加（基线恢复在7秒内）相当，但时间较短。然而，在Lc/+小鼠中，25脉冲齿状核诱发的前额叶皮层DA外排减弱了60%，在4秒内基线恢复，这表明齿状核向前额叶皮层的输出仍有部分功能。DA再摄取阻断剂增强了100脉冲刺激引起的前额皮质反应，而5 -羟色胺或去甲肾上腺素再摄取阻断剂没有作用，表明电流记录对DA的特异性。结果提供了神经化学证据，证明小脑可以调节前额叶皮层的DA外排。总之，这些发现可以解释为什么小脑和额叶皮层病变同时发生，并可能提供一种解释多种发育障碍常见症状多样性的机制。
Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 μA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked pre-frontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.
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DOI：
10.1111/j.1469-7610.1989.tb00771.x
发表时间：
1989-01-01
影响因子：
7.6
作者：
BOUCHER, J;LEWIS, V
通讯作者：
LEWIS, V
影响因子：
158.5
作者：
COURCHESNE, E;YEUNGCOURCHESNE, R;JERNIGAN, TL
通讯作者：
JERNIGAN, TL
影响因子：
3.3
作者：
del Arco, A;Mora, F
通讯作者：
Mora, F
影响因子：
3.8
作者：
JONES, MW;KILPATRICK, IC;PHILLIPSON, OT
通讯作者：
PHILLIPSON, OT
影响因子：
2.5
作者：
Feenstra, MGP;vanderWeij, W;Botterblom, MHA
通讯作者：
Botterblom, MHA