The inhibitory influence of the lateral habenula on midbrain dopamine cells: ultrastructural evidence for indirect mediation via the rostromedial mesopontine tegmental nucleus.
The inhibitory influence of the lateral habenula on midbrain dopamine cells: ultrastructural evidence for indirect mediation via the rostromedial mesopontine tegmental nucleus.
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DOI：
10.1002/cne.22561
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发表时间：
2011-04-15
影响因子：
2.5
通讯作者：
Sesack, Susan R.
中科院分区：
文献类型：
--
作者：
Balcita-Pedicino, Judith Joyce;Omelchenko, Natalia;Bell, Roland;Sesack, Susan R.
外侧缰核（LHb）是黑质和腹侧被盖区（VTA）中脑多巴胺（DA）细胞负强化信号的重要来源。这种显著且持续的抑制性影响涉及从LHb的谷氨酸神经元到某些γ - 氨基丁酸（GABA）细胞群的双突触连接，而这些GABA细胞又支配着DA神经元。先前的研究表明，VTA内固有的GABA细胞从LHb接收的突触输入不足，无法作为这种中间连接的主要来源。在这项研究中，我们寻找超微结构证据来支持这样一种假设：新发现的脑干区域，即吻内侧中脑桥被盖核（RMTg），更有可能是在LHb激活时抑制中脑DA细胞的候选区域。对含有顺行示踪剂和表型标记双重免疫反应性的大鼠脑切片进行电子显微镜检查发现：1）RMTg中LHb轴突形成的突触有55%以上位于GABA标记的树突上；2）VTA中RMTg轴突形成的突触有80%以上与对DA合成酶酪氨酸羟化酶有免疫反应的树突相接触；3）几乎所有RMTg轴突都形成对称突触，并且在包埋后对GABA有免疫反应性。这些发现表明，新确定的RMTg区域是连接LHb和VTA DA神经元的双突触通路中的一个中间结构。这些结果对于理解以涉及LHb和DA细胞群的奖赏回路失调为特征的精神障碍具有重要意义。
The lateral habenula (LHb) provides an important source of negative reinforcement signals to midbrain dopamine (DA) cells in the substantia nigra and ventral tegmental area (VTA). This profound and consistent inhibitory influence involves a disynaptic connection from glutamate neurons in the LHb to some population of γ-aminobutyric acid (GABA) cells that, in turn, innervates DA neurons. Previous studies demonstrated that the GABA cells intrinsic to the VTA receive insufficient synaptic input from the LHb to serve as the primary source of this intermediate connection. In this investigation, we sought ultrastructural evidence supporting the hypothesis that a newly identified region of the brainstem, the rostromedial mesopontine tegmental nucleus (RMTg), is a more likely candidate for inhibiting midbrain DA cells in response to LHb activation. Electron microscopic examination of rat brain sections containing dual immunoreactivity for an anterograde tracing agent and a phenotypic marker revealed that: 1) more than 55% of the synapses formed by LHb axons in the RMTg were onto GABA-labeled dendrites; 2) more than 80% of the synapses formed by RMTg axons in the VTA contacted dendrites immunoreactive for the DA synthetic enzyme tyrosine hydroxylase; and 3) nearly all RMTg axons formed symmetric synapses and contained postembedding immunoreactivity for GABA. These findings indicate that the newly identified RMTg region is an intermediate structure in a disynaptic pathway that connects the LHb to VTA DA neurons. The results have important implications for understanding mental disorders characterized by a dysregulation of reward circuitry involving LHb and DA cell populations.
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影响因子：
2.5
作者：
Blurton-Jones, Mathew;Tuszynsk, Mark H.
通讯作者：
Tuszynsk, Mark H.
影响因子：
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作者：
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影响因子：
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通讯作者：
Sesack, SR
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作者：
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通讯作者：
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作者：
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