Histological analyses of reinforcement circuitry

我们这个项目的主要目的是确定参与药物强化的详细神经连接。行为研究表明，中脑边缘多巴胺系统是功能异质性的。腹侧纹状体的内侧部分，包括内侧嗅球壳和内侧嗅结节，比外侧腹侧纹状体，包括嗅球核，腹侧壳和外侧结节，更负责精神兴奋剂的初级强化作用。在多巴胺细胞体区域，后腹侧被盖区和中央线性中缝核比前腹侧被盖区更负责一些药物，包括阿片类药物和胆碱能药物的增强作用。基于这些行为发现，我们假设腹侧纹状体中的奖励触发区（即，内侧嗅球壳和内侧嗅结节）接收来自腹侧中脑中的奖励触发区的投射（即，后腹侧被盖区和中央线状核）。当逆行示踪剂荧光金（FG）沉积到内侧腹侧纹状体（内侧壳或内侧结节），FG填充的细胞被发现主要在VTA和中央线性核的后内侧室。另一方面，当FG沉积到侧腹侧纹状体（核心，侧壳，或侧结节），FG填充的细胞被发现主要是在VTA的外侧部分。我们的研究结果表明，在内侧腹侧纹状体的奖励触发区接收来自奖励触发区在后内侧腹侧中脑的输入。

Our major aim of this project is to determine detailed neural connections involved in drug reinforcement. Behavioral studies indicate that the mesolimbic dopamine system is functionally heterogeneous. The medial portion of the ventral striatum, which includes the medial accumbens shell and medial olfactory tubercle, is more responsible for primary reinforcing effects of psychomotor stimulants than the lateral ventral striatum, which includes the accumbens core, ventral shell, and lateral tubercle. In the dopamine cell-body region, the posterior VTA and the central linear nucleus raphe are more responsible than the anterior VTA for the reinforcing effects of a number of drugs including opiates and cholinergic agents. Based on these behavioral findings, we hypothesize that the reward-trigger zones in the ventral striatum (i.e., the medial accumbens shell and medial olfactory tubercle) receives projections from the reward-trigger zones in the ventral midbrain (i.e., the posterior VTA and central linear nucleus). When the retrograde tracer Fluorogold (FG) was deposited into the medial ventral striatum (the medial shell or medial tubercle), FG-filled cells were found largely in the posteromedial compartment of the VTA and the central linear nucleus. On the other hand, when FG was deposited into the lateral ventral striatum (the core, lateral shell, or lateral tubercle), FG-filled cells were found mostly in the lateral portion of the VTA. Our results suggest that the reward-trigger zones in the medial ventral striatum receive input from the reward-trigger zones in the posteromedial ventral midbrain.