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对 VTA 中神经递质特异性投射的解剖分辨率揭示了 GABA 能传入的多样性。

Anatomic resolution of neurotransmitter-specific projections to the VTA reveals diversity of GABAergic inputs.

机构信息

Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.

Department of Pharmacology, University of Washington, Seattle, WA, USA.

出版信息

Nat Neurosci. 2020 Aug;23(8):968-980. doi: 10.1038/s41593-020-0657-z. Epub 2020 Jun 15.

Abstract

The ventral tegmental area (VTA) is important for reward processing and motivation. The anatomic organization of neurotransmitter-specific inputs to the VTA remains poorly resolved. In the present study, we mapped the major neurotransmitter projections to the VTA through cell-type-specific retrograde and anterograde tracing. We found that glutamatergic inputs arose from a variety of sources and displayed some connectivity biases toward specific VTA cell types. The sources of GABAergic projections were more widespread, displayed a high degree of differential innervation of subregions in the VTA and were largely biased toward synaptic contact with local GABA neurons. Inactivation of GABA release from the two major sources, locally derived versus distally derived, revealed distinct roles for these projections in behavioral regulation. Optogenetic manipulation of individual distal GABAergic inputs also revealed differential behavioral effects. These results demonstrate that GABAergic projections to the VTA are a major contributor to the regulation and diversification of the structure.

摘要

腹侧被盖区(VTA)对奖励处理和动机很重要。神经递质特异性传入 VTA 的解剖组织仍然没有得到很好的解决。在本研究中,我们通过细胞类型特异性逆行和顺行示踪来绘制 VTA 的主要神经递质投射。我们发现谷氨酸能输入来自多种来源,并对特定 VTA 细胞类型表现出一定的连接偏好。GABA 能投射的来源更为广泛,对 VTA 亚区的高度差异支配,并主要偏向与局部 GABA 神经元的突触接触。从两个主要来源,局部来源和远位来源,抑制 GABA 释放,揭示了这些投射在行为调节中的不同作用。对单个远位 GABA 能传入的光遗传学操纵也显示出不同的行为影响。这些结果表明,GABA 能投射到 VTA 是调节和多样化结构的主要贡献者。

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