The ventral pallidum (VP) is a central hub in the reward circuitry with diverse projections that have different behavioral roles attributed mostly to the connectivity with the downstream target. However, different VP projections may represent, as in the striatum, separate neuronal populations that differ in more than just connectivity. In this study, we performed in mice of both sexes a multimodal dissection of four major projections of the VP—to the lateral hypothalamus (VP_->LH), ventral tegmental area (VP_->VTA), lateral habenula (VP_->LHb), and mediodorsal thalamus (VP_->MDT)—with physiological, anatomical, genetic, and behavioral tools. We also tested for physiological differences between VP neurons receiving input from nucleus accumbens medium spiny neurons (MSNs) that express either the D1 (D1-MSNs) or the D2 (D2-MSNs) dopamine receptor. We show that each VP projection (1) when inhibited during a cocaine conditioned place preference (CPP) test affects performance differently, (2) receives a different pattern of inputs using rabies retrograde labeling, (3) shows differentially expressed genes using RNA sequencing, and (4) has projection-specific characteristics in excitability and synaptic input characteristics using whole-cell patch clamp. VP_->LH and VP_->VTA projections have different effects on CPP and show low overlap in circuit tracing experiments, as VP_->VTA neurons receive more striatal input, while VP_->LH neurons receive more olfactory input. Additionally, VP_->VTA neurons are less excitable, while VP_->LH neurons are more excitable than the average VP neuron, a difference driven mainly by D2-MSN-responding neurons. Thus, VP_->VTA and VP_->LH neurons may represent largely distinct populations of VP neurons.

腹侧苍白球（VP）是奖励回路的中心枢纽，具有不同的投射，具有不同的行为作用，主要归因于与下游目标的连接。然而，不同的 VP 预测可能代表不同的神经元群体，就像在纹状体中一样，这些神经元群体的不同之处不仅仅是连接性。在这项研究中，我们对两性小鼠进行了 VP 四个主要投影的多模式解剖——外侧下丘脑 (VP _->LH )、腹侧被盖区 (VP _->VTA )、外侧缰核 (VP _->LHb）和内侧丘脑（VP _->MDT）——使用生理、解剖、遗传和行为工具。我们还测试了从表达 D1 (D1-MSN) 或 D2 (D2-MSN) 多巴胺受体的伏隔核中型多棘神经元 (MSN) 输入的 VP 神经元之间的生理差异。我们表明，每个 VP 投射 (1) 在可卡因条件位置偏好 (CPP) 测试期间受到抑制时，对表现的影响不同，(2) 使用狂犬病逆行标记接收不同的输入模式，(3) 使用 RNA 测序显示差异表达的基因， (4)使用全细胞膜片钳在兴奋性和突触输入特征方面具有投射特异性特征。 VP _->LH和 VP _->VTA投影对 CPP 有不同的影响，并且在电路追踪实验中显示出较低的重叠，因为 VP _->VTA神经元接收更多的纹状体输入，而 VP _->LH神经元接收更多的嗅觉输入。此外，VP _->VTA神经元的兴奋性较低，而 VP _->LH神经元比平均 VP 神经元更容易兴奋，这种差异主要由 D2-MSN 响应神经元驱动。因此，VP _->VTA和 VP _->LH神经元可能代表了很大程度上不同的 VP 神经元群体。