腹侧苍白球(VP)是奖励回路中的中心枢纽,具有不同的预测,这些预测具有不同的行为角色,主要归因于与下游目标的连通性。然而,不同的VP预测可能代表,就像纹状体一样,不同的神经元群体不仅仅是连通性。在这项研究中,我们在两种性别的小鼠中对VP的四个主要投影进行了多模态解剖-到下丘脑外侧(VP→LH),腹侧被盖区(VP→VTA),外侧(VP→LHb)和中背丘脑(VP→MDT)-具有生理,解剖学,遗传和行为工具。我们还测试了接收来自伏隔核(NAc)中等多刺神经元(MSN)的输入的VP神经元之间的生理差异,这些神经元表达D1(D1-MSN)或D2(D2-MSN)多巴胺受体。我们表明,每个VP投影1)在可卡因条件位置偏好(CPP)测试中受到抑制时,会对性能产生不同的影响;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,并且在电路跟踪实验中显示出低重叠,当VP→VTA神经元接收更多纹状体输入,而VP→LH神经元接收更多嗅觉输入。此外,VP→VTA神经元的兴奋性较低,而VP→LH神经元的兴奋性较平均VP神经元高,差异主要由D2-MSN响应神经元驱动。因此,VP→VTA和VP→LH神经元可能代表了大部分不同的VP神经元群体。重要性陈述神经科学中的许多现代研究将不同的行为角色分配给特定的电路。这些行为角色通常归因于两个大脑区域之间的连接,尽管不同的预测在其他方面也可能不同,并且可能源于,就像在纹状体里,来自大部分独立的神经元群体。腹侧苍白球(VP)是奖励系统的主要结构,可将投影发送到许多不同的目标。在这项工作中,我们首次对VP的四个主要输出进行了全面的多峰表征,有证据表明预测之间存在各种差异。我们还建议其中两个预测,腹侧被盖区和下丘脑外侧起源于很大程度上独立的神经元群体。
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.