Identification of discrete, intermingled hypocretin neuronal populations
Identification of discrete, intermingled hypocretin neuronal populations
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DOI：
10.1002/cne.24490
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发表时间：
2018-12-15
影响因子：
2.5
通讯作者：
Carter, Matthew E.
中科院分区：
文献类型：
--
作者：
Iyer, Manasi;Essner, Rachel A.;Carter, Matthew E.
下丘脑外侧区表达下丘脑泌素（Hcrt）神经肽的神经元有助于调节许多行为，包括觉醒和奖励寻求。这些神经元投射到整个大脑，包括调节觉醒的神经群，如蓝斑（LC）和结节乳核（TMN），以及调节奖励的神经群，如延髓核（NAc）和腹侧被盖区（VTA）。为了解决Hcrt神经元在看似不同的行为中的作用，已经提出Hcrt神经元可以在解剖学上细分为至少两个不同的亚群：投射到LC和TMN的“内侧组”，以及投射到NAc和VTA的“外侧组”。在这里，我们使用双重逆行示踪剂策略来测试的假设，Hcrt神经元可以根据其下游的预测和内侧/外侧的位置在下丘脑内进行分类。我们发现，个别Hcrt神经元显着更有可能投射到LC和TMN或VTA和NAc比预测的机会。与此相反，我们发现，Hcrt神经元，投射到LC或TMN大多是不同的Hcrt神经元，投射到VTA或NAc。有趣的是，这两个群体的Hcrt神经元混合在下丘脑内，不能分为内侧或外侧组。这些结果表明，Hcrt神经元可以区分基于其下游的预测，但在下丘脑内混杂。
Neurons in the lateral hypothalamic area that express hypocretin (Hcrt) neuropeptides help regulate many behaviors including wakefulness and reward seeking. These neurons project throughout the brain, including to neural populations that regulate wakefulness, such as the locus coeruleus (LC) and tuberomammilary nucleus (TMN), as well as to populations that regulate reward, such as the nucleus accumbens (NAc) and ventral tegmental area (VTA). To address the roles of Hcrt neurons in seemingly disparate behaviors, it has been proposed that Hcrt neurons can be anatomically subdivided into at least two distinct subpopulations: a "medial group" that projects to the LC and TMN, and a "lateral group" that projects to the NAc and VTA. Here, we use a dual retrograde tracer strategy to test the hypotheses that Hcrt neurons can be classified based on their downstream projections and medial/lateral location within the hypothalamus. We found that individual Hcrt neurons were significantly more likely to project to both the LC and TMN or to both the VTA and NAc than would be predicted by chance. In contrast, we found that Hcrt neurons that projected to the LC or TMN were mostly distinct from Hcrt neurons that projected to the VTA or NAc. Interestingly, these two populations of Hcrt neurons are intermingled within the hypothalamus and cannot be classified into medial or lateral groups. These results suggest that Hcrt neurons can be distinguished based on their downstream projections but are intermingled within the hypothalamus.