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Neuron‐specific cilia loss differentially alters locomotor responses to amphetamine in mice
Journal of Neuroscience Research ( IF 4.2 ) Pub Date : 2020-11-11 , DOI: 10.1002/jnr.24755
Carlos Ramos 1 , Jonté B Roberts 1 , Kalene R Jasso 1 , Tyler W Ten Eyck 1 , Thomas Everett 1 , Patricia Pozo 1 , Barry Setlow 2, 3 , Jeremy C McIntyre 1, 3
Affiliation  

The neural mechanisms that underlie responses to drugs of abuse are complex, and impacted by a number of neuromodulatory peptides. Within the past 10 years it has been discovered that several of the receptors for neuromodulators are enriched in the primary cilia of neurons. Primary cilia are microtubule‐based organelles that project from the surface of nearly all mammalian cells, including neurons. Despite what we know about cilia, our understanding of how cilia regulate neuronal function and behavior is still limited. The primary objective of this study was to investigate the contributions of primary cilia on specific neuronal populations to behavioral responses to amphetamine. To test the consequences of cilia loss on amphetamine‐induced locomotor activity we selectively ablated cilia from dopaminergic or GAD2‐GABAergic neurons in mice. Cilia loss had no effect on baseline locomotion in either mouse strain. In mice lacking cilia on dopaminergic neurons, locomotor activity compared to wild‐ type mice was reduced in both sexes in response to acute administration of 3.0 mg/kg amphetamine. In contrast, changes in the locomotor response to amphetamine in mice lacking cilia on GAD2‐GABAergic neurons were primarily driven by reductions in locomotor activity in males. Following repeated amphetamine administration (1.0 mg kg−1 day−1 over 5 days), mice lacking cilia on GAD2‐GABAergic neurons exhibited enhanced sensitization of the locomotor stimulant response to the drug, whereas mice lacking cilia on dopaminergic neurons did not differ from wild‐type controls. These results indicate that cilia play neuron‐specific roles in both acute and neuroplastic responses to psychostimulant drugs of abuse.

中文翻译:

神经元特异性纤毛损失不同地改变小鼠对苯丙胺的运动反应

对滥用药物作出反应的神经机制很复杂,并受到许多神经调节肽的影响。在过去的 10 年中,人们发现神经调节剂的几种受体富含神经元的初级纤毛。初级纤毛是基于微管的细胞器,从几乎所有哺乳动物细胞(包括神经元)的表面突出。尽管我们对纤毛有所了解,但我们对纤毛如何调节神经元功能和行为的理解仍然有限。本研究的主要目的是调查初级纤毛对特定神经元群体对苯丙胺的行为反应的贡献。为了测试纤毛缺失对安非他明诱导的运动活动的影响,我们选择性地切除了小鼠多巴胺能或 GAD2-GABA 能神经元的纤毛。纤毛丢失对任一小鼠品系的基线运动没有影响。在多巴胺能神经元上缺乏纤毛的小鼠中,与野生型小鼠相比,在急性给予 3.0 mg/kg 苯丙胺后,两性的运动活动均降低。相比之下,GAD2-GABAergic 神经元上缺乏纤毛的小鼠对安非他明的运动反应的变化主要是由雄性运动活动的减少驱动的。重复服用苯丙胺后(1.0 mg kg 在 GAD2-GABA 能神经元上缺乏纤毛的小鼠对安非他明的运动反应的变化主要是由雄性运动活动的减少驱动的。重复服用苯丙胺后(1.0 mg kg 在 GAD2-GABA 能神经元上缺乏纤毛的小鼠对安非他明的运动反应的变化主要是由雄性运动活动的减少驱动的。重复服用苯丙胺后(1.0 mg kg-1 天-1超过 5 天),GAD2-GABA 能神经元上缺乏纤毛的小鼠表现出对药物的运动兴奋剂反应的敏感性增强,而多巴胺能神经元上缺乏纤毛的小鼠与野生型对照没有差异。这些结果表明纤毛在对滥用精神兴奋剂的急性和神经可塑性反应中都发挥神经元特异性作用。
更新日期:2020-11-11
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