Michigan State University Department of Pharmacology and Toxicology, East Lansing, 48824, MI, USA.
Institute for Integrative Toxicology at Michigan State University, East Lansing, 48824, MI, USA.
Sci Rep. 2019 Feb 12;9(1):1873. doi: 10.1038/s41598-018-38143-9.
The lateral hypothalamic area (LHA) is essential for ingestive behavior but it remains unclear how LHA neurons coordinate feeding vs. drinking. Most LHA populations promote food and water consumption but LHA neurotensin (Nts) neurons preferentially induce water intake while suppressing feeding. We identified two molecularly and projection-specified subpopulations of LHA Nts neurons that are positioned to coordinate either feeding or drinking. One subpopulation co-expresses the long form of the leptin receptor (LepRb) and is activated by the anorectic hormone leptin (Nts neurons). A separate subpopulation lacks LepRb and is activated by dehydration (Nts neurons). These molecularly distinct LHA Nts subpopulations also differ in connectivity: Nts neurons project to the ventral tegmental area and substantia nigra compacta but Nts neurons do not. Intriguingly, the LHA Nts subpopulations cannot be discriminated via their classical neurotransmitter content, as we found that all LHA Nts neurons are GABAergic. Collectively, our data identify two molecularly- and projection-specified subpopulations of LHA Nts neurons that intercept either leptin or dehydration cues, and which conceivably could regulate feeding vs. drinking behavior. Selective regulation of these LHA Nts subpopulations might be useful to specialize treatment for ingestive disorders such as polydipsia or obesity.
外侧下丘脑区域（LHA）对摄食行为至关重要，但目前尚不清楚 LHA 神经元如何协调进食和饮水。大多数 LHA 群体促进食物和水的消耗，但 LHA 神经降压素（Nts）神经元优先诱导饮水，同时抑制进食。我们鉴定出两种在分子水平和投射特异性上都有区别的 LHA Nts 神经元亚群，它们的位置可以协调进食或饮水。一个亚群共同表达长形式的瘦素受体（LepRb），并被厌食激素瘦素激活（Nts 神经元）。另一个亚群缺乏 LepRb，并且可以被脱水激活（Nts 神经元）。这些分子上不同的 LHA Nts 亚群在连接性上也有所不同：Nts 神经元投射到腹侧被盖区和黑质致密部，但 Nts 神经元不投射到这些部位。有趣的是，LHA Nts 亚群不能通过其经典神经递质含量来区分，因为我们发现所有 LHA Nts 神经元都是 GABA 能神经元。总的来说，我们的数据确定了两种在分子水平和投射特异性上都有区别的 LHA Nts 神经元亚群，它们可以截获瘦素或脱水线索，并且可以想象调节进食和饮水行为。这些 LHA Nts 亚群的选择性调节可能对专门治疗摄食障碍（如多饮症或肥胖症）有用。
