Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its Relevance for Schizophrenia.
Heterogeneity in Dopamine Neuron Synaptic Actions Across the Striatum and Its Relevance for Schizophrenia.
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DOI：
10.1016/j.biopsych.2016.07.002
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发表时间：
2017-01-01
影响因子：
10.6
通讯作者：
Rayport, Stephen
中科院分区：
文献类型：
--
作者：
Chuhma, Nao;Mingote, Susana;Kalmbach, Abigail;Yetnikoff, Leora;Rayport, Stephen
脑成像揭示了精神分裂症患者多巴胺摄取、释放和受体水平的改变，这些改变在纹状体亚区的尺度上得到了解决。然而，潜在的突触机制是在一个更精细的尺度。多巴胺神经元的突触活动在整个纹状体中各不相同，不仅涉及多巴胺释放的变化，还涉及多巴胺神经元的连接、共传递、调制和活性。光遗传学研究表明，多巴胺神经元以突触信号模式释放多巴胺，并且神经元还释放谷氨酸和GABA作为共递质，具有显著的区域差异。快速谷氨酸和GABA共传递传递离散模式的多巴胺神经元活动的纹状体神经元。谷氨酸不仅可以在多巴胺神经元突触的子集中起信号传导作用，而且还可以介导囊泡协同作用，从而导致多巴胺加载到突触囊泡中的区域差异。多巴胺神经元信号传导的区域差异可能与精神分裂症疾病过程有关，并可能决定精神兴奋剂作用的次区域特异性，精神兴奋剂会加重疾病，而抗精神病药物会改善疾病。阐明多巴胺神经元突触信号提供了通过靶向多巴胺神经元突触子集的交叉药理学作用实现更大药理学特异性的潜力。
Brain imaging has revealed alterations in dopamine uptake, release and receptor levels in patients with schizophrenia that have been resolved at the scale of striatal subregions. However, the underlying synaptic mechanisms are at a finer scale. Dopamine neuron synaptic actions vary across the striatum, involving not only variations in dopamine release, but also in dopamine neuron connectivity, cotransmission, modulation and activity. Optogenetic studies have revealed that dopamine neurons release dopamine in a synaptic signal mode, and that the neurons also release glutamate and GABA as cotransmitters, with striking regional variation. Fast glutamate and GABA cotransmission convey discrete patterns of dopamine neuron activity to striatal neurons. Glutamate may function not only in a signaling role at a subset of dopamine neuron synapses, but also in mediating vesicular synergy, contributing to regional differences in loading of dopamine into synaptic vesicles. Regional differences in dopamine neuron signaling are likely to be differentially involved in the schizophrenia disease process, and likely determine the subregional specificity of the action of psychostimulants that exacerbate the disorder, and antipsychotics that ameliorate the disorder. Elucidating dopamine neuron synaptic signaling offers the potential for achieving greater pharmacological specificity through intersectional pharmacological actions targeting subsets of dopamine neuron synapses.
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影响因子：
16.2
作者：
Chuhma N;Mingote S;Moore H;Rayport S
通讯作者：
Rayport S
纹状体培养基神经元的功能连接组。
DOI：
10.1523/jneurosci.3833-10.2011
发表时间：
2011-01-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chuhma N;Tanaka KF;Hen R;Rayport S
通讯作者：
Rayport S
影响因子：
5.3
作者：
Baliki, Marwan N.;Mansour, Ali;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania
影响因子：
5.3
作者：
Chuhma, N;Zhang, H;Rayport, S
通讯作者：
Rayport, S
DOI：
10.1073/pnas.0910986107
发表时间：
2010-01-05
影响因子：
11.1
作者：
Birgner, Carolina;Nordenankar, Karin;Wallen-Mackenzie, Asa
通讯作者：
Wallen-Mackenzie, Asa