Neuron-specific cilia loss differentially alters locomotor responses to amphetamine in mice.
Neuron-specific cilia loss differentially alters locomotor responses to amphetamine in mice.
复制标题
神经元特异性纤毛丢失不同地改变了小鼠对苯丙胺的运动反应。
DOI：
10.1002/jnr.24755
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发表时间：
2021-03
影响因子：
4.2
通讯作者：
McIntyre JC
中科院分区：
文献类型：
--
作者：
Ramos C;Roberts JB;Jasso KR;Ten Eyck TW;Everett T;Pozo P;Setlow B;McIntyre JC
对滥用药物的反应背后的神经机制是复杂的，并受到许多神经调节肽的影响。在过去的十年里，人们发现神经调节剂的几种受体在神经元的初级纤毛中丰富。初级纤毛是以微管为基础的细胞器，从几乎所有哺乳动物细胞的表面伸出，包括神经元。尽管我们知道纤毛，但我们对纤毛如何调节神经元功能和行为的了解仍然有限。这项研究的主要目的是调查特定神经元群体上的初级纤毛对苯丙胺行为反应的贡献。为了测试纤毛丧失对苯丙胺诱导的运动活动的影响，我们选择性地消融了小鼠多巴胺能或GAD2-GABA能神经元的纤毛。纤毛丧失对两个品系的小鼠的基线运动都没有影响。在缺乏多巴胺能神经元纤毛的小鼠中，与野生型小鼠相比，急性注射3.0 mg/kg苯丙胺后，两性小鼠的运动活动都有所减少。相比之下，缺乏纤毛的小鼠GAD2-GABA能神经元对苯丙胺的运动反应的变化主要是由雄性运动活动的减少驱动的。在反复给予苯丙胺(每天1.0 mg/kg，连续5天)后，GAD2-GABA能神经元上缺乏纤毛的小鼠表现出对药物的运动刺激反应的敏感化，而多巴胺能神经元上缺乏纤毛的小鼠与野生型对照组没有区别。这些结果表明，纤毛在滥用精神刺激性药物的急性和神经可塑性反应中发挥神经元特异性作用。所有神经元都有一个初级纤毛，它从细胞体投射到细胞外空间。这项研究调查了被设计为缺乏初级纤毛的小鼠对注射苯丙胺后GAD2表达的GABA能神经元或多巴胺能神经元的行为反应。
The neural mechanisms that underlie responses to drugs of abuse are complex, and impacted by a number of neuromodulatory peptides. Within the past ten 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/day 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 wildtype controls. These results indicate that cilia play neuron-specific roles in both acute and neuroplastic responses to psychostimulant drugs of abuse. All neurons possess a primary cilium that projects from the cell body into the extracellular space. This study investigates the behavioral responses of mice engineered to lack a primary cilium on either Gad2 expressing GABAergic neurons, or Dopaminergic neurons, to injections of amphetamine.
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影响因子：
3.1
作者：
Ehrlich AT;Semache M;Bailly J;Wojcik S;Arefin TM;Colley C;Le Gouill C;Gross F;Lukasheva V;Hogue M;Darcq E;Harsan LA;Bouvier M;Kieffer BL
通讯作者：
Kieffer BL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2
作者：
Brinckman, Danielle D.;Keppler-Noreuil, Kim M.;Blumhorst, Catherine;Biesecker, Leslie G.;Sapp, Julie C.;Johnston, Jennifer J.;Wiggs, Edythe A.
通讯作者：
Wiggs, Edythe A.
影响因子：
2.9
作者：
Carr, KD
通讯作者：
Carr, KD
影响因子：
3.7
作者：
Berbari NF;Malarkey EB;Yazdi SM;McNair AD;Kippe JM;Croyle MJ;Kraft TW;Yoder BK
通讯作者：
Yoder BK