Qualls-Creekmore Emily, Yu Sangho, Francois Marie, Hoang John, Huesing Clara, Bruce-Keller Annadora, Burk David, Berthoud Hans-Rudolf, Morrison Christopher D, Münzberg Heike
Neurobiology of Nutrition and Metabolism, and
Neurobiology of Nutrition and Metabolism, and.
J Neurosci. 2017 Jun 21;37(25):6053-6065. doi: 10.1523/JNEUROSCI.0155-17.2017. Epub 2017 May 24.
The lateral hypothalamus (LHA) integrates reward and appetitive behavior and is composed of many overlapping neuronal populations. Recent studies associated LHA GABAergic neurons (LHA ), which densely innervate the ventral tegmental area (VTA), with modulation of food reward and consumption; yet, LHA projections to the VTA exclusively modulated food consumption, not reward. We identified a subpopulation of LHA neurons that coexpress the neuropeptide galanin (LHA ). These LHA neurons also modulate food reward, but lack direct VTA innervation. We hypothesized that LHA neurons may represent a subpopulation of LHA neurons that mediates food reward independent of direct VTA innervation. We used chemogenetic activation of LHA or LHA neurons in mice to compare their role in feeding behavior. We further analyzed locomotor behavior to understand how differential VTA connectivity and transmitter release in these LHA neurons influences this behavior. LHA or LHA neuronal activation both increased operant food-seeking behavior, but only activation of LHA neurons increased overall chow consumption. Additionally, LHA or LHA neuronal activation similarly induced locomotor activity, but with striking differences in modality. Activation of LHA neurons induced compulsive-like locomotor behavior; while LHA neurons induced locomotor activity without compulsivity. Thus, LHA neurons define a subpopulation of LHA neurons without direct VTA innervation that mediate noncompulsive food-seeking behavior. We speculate that the striking difference in compulsive-like locomotor behavior is also based on differential VTA innervation. The downstream neural network responsible for this behavior and a potential role for galanin as neuromodulator remains to be identified. The lateral hypothalamus (LHA) regulates motivated feeding behavior via GABAergic LHA neurons. The molecular identity of LHA neurons is heterogeneous and largely undefined. Here we introduce LHA neurons as a subset of LHA neurons that lack direct innervation of the ventral tegmental area (VTA). LHA neurons are sufficient to drive motivated feeding and locomotor activity similar to LHA neurons, but without inducing compulsive-like behaviors, which we propose to require direct VTA innervation. Our study integrates galanin-expressing LHA neurons into our current understanding of the neuronal circuits and molecular mechanisms of the LHA that contribute to motivated feeding behaviors.
外侧下丘脑（LHA）整合奖赏和食欲行为，由许多重叠的神经元群体组成。最近的研究将密集支配腹侧被盖区（VTA）的LHAγ-氨基丁酸能神经元（LHA ）与食物奖赏和消耗的调节联系起来；然而，LHA 向VTA的投射仅调节食物消耗，而非奖赏。我们鉴定出了一个共表达神经肽甘丙肽的LHA 神经元亚群（LHA ）。这些LHA 神经元也调节食物奖赏，但缺乏对VTA的直接支配。我们推测LHA 神经元可能代表LHA 神经元的一个亚群，其介导食物奖赏而不依赖于对VTA的直接支配。我们利用化学遗传学方法激活小鼠的LHA 或LHA 神经元，以比较它们在摄食行为中的作用。我们进一步分析了运动行为，以了解这些LHA神经元中不同的VTA连接性和神经递质释放如何影响这种行为。LHA 或LHA 神经元的激活均增加了操作性觅食行为，但只有LHA 神经元的激活增加了总的食物摄入量。此外，LHA 或LHA 神经元的激活同样诱导了运动活动，但在方式上有显著差异。LHA 神经元的激活诱导了强迫样运动行为；而LHA 神经元诱导的运动活动没有强迫性。因此，LHA 神经元定义了LHA 神经元的一个亚群，其没有对VTA的直接支配，介导非强迫性觅食行为。我们推测强迫样运动行为的显著差异也基于不同的VTA支配。负责这种行为的下游神经网络以及甘丙肽作为神经调节剂的潜在作用仍有待确定。外侧下丘脑（LHA）通过γ-氨基丁酸能LHA神经元调节动机性摄食行为。LHA 神经元的分子特征是异质性的，且在很大程度上尚未明确。在这里，我们将LHA 神经元作为LHA 神经元的一个子集引入，其缺乏对腹侧被盖区（VTA）的直接支配。LHA 神经元足以驱动与LHA 神经元相似的动机性摄食和运动活动，但不会诱导强迫样行为，我们认为这需要对VTA的直接支配。我们的研究将表达甘丙肽的LHA神经元整合到我们目前对LHA神经元回路和分子机制的理解中，这些机制有助于动机性摄食行为。
