Dopamine-glutamate neuron projections to the nucleus accumbens medial shell and behavioral switching
Dopamine-glutamate neuron projections to the nucleus accumbens medial shell and behavioral switching
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DOI：
10.1016/j.neuint.2019.104482
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发表时间：
2019-10-01
影响因子：
4.2
通讯作者：
Chuhma, Nao
中科院分区：
文献类型：
--
作者：
Mingote, Susana;Amsellem, Aliza;Chuhma, Nao
多巴胺（DA）神经元向纹状体的投射在功能上是异质的，具有不同的行为作用。我们将重点研究DA神经元向伏隔核（NAc）内侧壳的投射，它们之间独特的解剖和功能联系，并讨论它们在动机行为中的作用。我们首先回顾啮齿类动物的研究，表明内侧腹侧被盖区（VTA）的DA神经元亚群投射到NAc内侧壳。通过组合策略，我们发现大多数投射到NAc壳的DA神经元表达谷氨酸囊泡转运蛋白2 (VGLUT2)，使它们能够进行谷氨酸共传递（DA- glu神经元）。在NAc背内侧壳中，DA神经元末梢均来自DA- glu神经元，而在NAc外侧壳中，DA神经元末梢均来自DA- glu神经元和DA-only神经元，不含VGLUT2。DA-GLU神经元与三种主要的细胞类型，刺状投射神经元，快速尖峰间神经元和胆碱能间神经元（ChIs）建立兴奋性连接。最强的DA-GLU神经元兴奋性连接是与ChIs。片内DA-GLU神经元末梢的光刺激可导致ChIs爆发。最后，我们回顾了这一亚群神经元在灭绝学习和潜在抑制中的行为功能。考虑到解剖学和功能连接组研究的结果，我们提出DA-GLU神经元与内侧壳中ChIs的连接在改变提示强化偶发情况下的行为反应转换中起着至关重要的作用。
Dopamine (DA) neuron projections to the striatum are functionally heterogeneous with diverse behavioral roles. We focus here on DA neuron projections to the nucleus accumbens (NAc) medial Shell, their distinct anatomical and functional connections, and discuss their role in motivated behavior. We first review rodent studies showing that a subpopulation of DA neurons in the medial ventral tegmental area (VTA) project to the NAc medial Shell. Using a combinatorial strategy, we show that the majority of DA neurons projecting to the NAc Shell express vesicular glutamate transporter 2 (VGLUT2) making them capable of glutamate co-transmission (DA-GLU neurons). In the NAc dorsal medial Shell, all of the DA neuron terminals arise from DA-GLU neurons, while in the lateral NAc Shell, DA neuron terminals arise from both DA-GLU neurons and DA-only neurons, without VGLUT2. DA-GLU neurons make excitatory connections to the three major cells types, spiny projection neurons, fast-spiking intemeuron and cholinergic interneurons (ChIs). The strongest DA-GLU neuron excitatory connections are to ChIs. Photostimulation of DA-GLU neuron terminals in the slice drives ChIs to burst fire. Finally, we review studies that address specially the behavioral function of this subpopulation of DA neurons in extinction learning and latent inhibition. Taking into account findings from anatomical and functional connectome studies, we propose that DA-GLU neuron connections to ChIs in the medial Shell play a crucial role in switching behavioral responses under circumstances of altered cue-reinforcer contingencies.