Del Monte Institute for Neuroscience, University of Rochester, Rochester, NY 14642
Del Monte Institute for Neuroscience, University of Rochester, Rochester, NY 14642.
J Neurosci. 2022 Nov 30;42(48):8997-9010. doi: 10.1523/JNEUROSCI.1453-22.2022. Epub 2022 Oct 24.
The central extended amygdala (CEA) and ventral pallidum (VP) are involved in diverse motivated behaviors based on rodent models. These structures are conserved, but expanded, in higher primates, including human. Corticotropin releasing factor (CRF), a canonical "stress molecule" associated with the CEA and VP circuitry across species, is dynamically regulated by stress and drugs of abuse and misuse. CRF's effects on circuits critically depend on its colocation with primary "fast" transmitters, making this crucial for understanding circuit effects. We surveyed the distribution and colocalization of CRF-, VGluT2- (vesicular glutamate transporter 2), and VGAT- (vesicular GABA transporter) mRNA in specific subregions of the CEA and VP in young male monkeys. Although CRF-containing neurons were clustered in the lateral central bed nucleus (BSTLcn), the majority were broadly dispersed throughout other CEA subregions, and the VP. CRF/VGAT-only neurons were highest in the BSTLcn, lateral central amygdala nucleus (CeLcn), and medial central amygdala nucleus (CeM) (74%, 73%, and 85%, respectively). In contrast, lower percentages of CRF/VGAT only neurons populated the sublenticular extended amygdala (SLEAc), ventrolateral bed nucleus (BSTLP), and VP (53%, 54%, 17%, respectively), which had higher complements of CRF/VGAT/VGluT2-labeled neurons (33%, 29%, 67%, respectively). Thus, the majority of CRF-neurons at the "poles" (BSTLcn and CeLcn/CeM) of the CEA are inhibitory, while the "extended" BSTLP and SLEAc subregions, and neighboring VP, have a more complex profile with admixtures of "multiplexed" excitatory CRF neurons. CRF's colocalization with its various fast transmitters is likely circuit-specific, and relevant for understanding CRF actions on specific target sites. The central extended amygdala (CEA) and ventral pallidum (VP) regulate multiple motivated behaviors through differential downstream projections. The stress neuropeptide corticotropin releasing factor (CRF) is enriched in the CEA, and is thought to "set the gain" through modulatory effects on coexpressed primary transmitters. Using protein and transcript assays in monkey, we found that CRF neurons are broadly and diffusely distributed in CEA and VP. CRF mRNA neurons colocalize with VGAT (GABA) and VGluT2 (glutamate) mRNAs in different proportions depending on subregion. CRF mRNA was also coexpressed in a subpopulation of VGAT/VGluT2 mRNA ("multiplexed") cells, which were most prominent in the VP and "pallidal"-like parts of the CEA. Heterogeneous CRF and fast transmitter coexpression across CEA/VP subregions implies circuit-specific effects.
中央延伸杏仁核（CEA）和腹侧苍白球（VP）基于啮齿动物模型参与各种动机行为。这些结构在包括人类在内的高等灵长类动物中是保守的，但却有所扩展。促肾上腺皮质释放因子（CRF）是一种与 CEA 和 VP 回路相关的典型“应激分子”，在物种间其动态受到应激和滥用药物的调节。CRF 对回路的影响极大地取决于其与主要“快速”递质的共定位，这对于理解回路效应至关重要。我们调查了年轻雄性猴子 CEA 和 VP 特定亚区中 CRF、VGluT2（囊泡谷氨酸转运体 2）和 VGAT（囊泡 GABA 转运体）mRNA 的分布和共定位。虽然含有 CRF 的神经元聚集在外侧中央床核（BSTLcn）中，但大多数神经元广泛分布在其他 CEA 亚区和 VP 中。CRF/VGAT 仅神经元在 BSTLcn、外侧中央杏仁核核（CeLcn）和内侧中央杏仁核核（CeM）中最高（分别为 74%、73%和 85%）。相比之下，亚核延伸杏仁核（SLEAc）、腹外侧床核（BSTLP）和 VP 中的 CRF/VGAT 仅神经元的比例较低（分别为 53%、54%和 17%），其中含有 CRF/VGAT/VGluT2 标记神经元的比例较高（分别为 33%、29%和 67%）。因此，CEA“极点”（BSTLcn 和 CeLcn/CeM）的大多数 CRF 神经元是抑制性的，而“扩展”的 BSTLP 和 SLEAc 亚区以及邻近的 VP 具有更复杂的特征，混合了“多路复用”兴奋性 CRF 神经元。CRF 与其各种快速递质的共定位可能是特定于回路的，这对于理解 CRF 对特定靶位的作用很重要。中央延伸杏仁核（CEA）和腹侧苍白球（VP）通过不同的下游投射调节多种动机行为。应激神经肽促肾上腺皮质释放因子（CRF）在 CEA 中丰富，并通过对共表达的主要递质的调节作用“设定增益”。使用猴子中的蛋白质和转录物测定，我们发现 CRF 神经元在 CEA 和 VP 中广泛且弥散地分布。CRF mRNA 神经元与 VGAT（GABA）和 VGluT2（谷氨酸）mRNA 按不同比例共定位，这取决于亚区。CRF mRNA 也在 VGAT/VGluT2 mRNA 的亚群（“多路复用”）细胞中共表达，在 VP 和 CEA 的“苍白球样”部分最为明显。CEA/VP 亚区中 CRF 和快速递质的异质性共表达暗示了特定于回路的效应。
