外侧缰带表达pacap的神经元减少负性情绪效价

IF 2.4 4区 心理学 Q2 BEHAVIORAL SCIENCES
Marjorie R. Levinstein, David J. Bergkamp, Zoë K. Lewis, Alex Tsobanoudis, Koichi Hashikawa, Garret D. Stuber, John F. Neumaier
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引用次数: 6

摘要

侧缰核(LHb)是一个小的,双侧的上皮核,处理厌恶信息。虽然主要是谷氨酸能,但LHb神经元表达编码许多神经肽的基因,如Adcyap1,该基因编码垂体腺苷酸环化酶激活多肽(PACAP),其本身与焦虑和应激障碍有关。利用cre依赖的病毒载体,我们根据这些神经元的解剖投影对其进行了定位和表征,发现它们同时投射到中缝和前内侧被盖区,但仅微弱地投射到腹侧被盖区。使用RiboTag从这些神经元中捕获核糖体相关mRNA,并重新分析现有的单细胞RNA测序数据,我们没有发现LHb中这些表达pacap的神经元具有独特的分子表型。为了了解这些神经元的功能,我们在LHb pacap -表达神经元中选择性地表达hM3Dq - DREADD,并在开放场实验、情境恐惧条件反射、蔗糖偏好、新奇抑制摄食和条件位置偏好的行为测试中对这些神经元进行化学刺激。我们发现,Gq激活的这些神经元产生的行为与LHb的整体预期相反——它们减少了焦虑和恐惧行为,并产生了条件性的位置偏好。总之,在LHb中表达pacap的神经元代表了一种分子多样化的细胞群,它们通过奖励或减少厌恶事件的负面后果来反对LHb神经元的其余行为。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PACAP-expressing neurons in the lateral habenula diminish negative emotional valence

PACAP-expressing neurons in the lateral habenula diminish negative emotional valence

The lateral habenula (LHb) is a small, bilateral, epithalamic nucleus which processes aversive information. While primarily glutamatergic, LHb neurons express genes coding for many neuropeptides, such as Adcyap1 the gene encoding pituitary adenylate cyclase-activating polypeptide (PACAP), which itself has been associated with anxiety and stress disorders. Using Cre-dependent viral vectors, we targeted and characterized these neurons based on their anatomical projections and found that they projected to both the raphe and rostromedial tegmentum but only weakly to ventral tegmental area. Using RiboTag to capture ribosomal-associated mRNA from these neurons and reanalysis of existing single cell RNA sequencing data, we did not identify a unique molecular phenotype that characterized these PACAP-expressing neurons in LHb. In order to understand the function of these neurons, we conditionally expressed hM3Dq DREADD selectively in LHb PACAP-expressing neurons and chemogenetically excited these neurons during behavioral testing in the open field test, contextual fear conditioning, sucrose preference, novelty suppressed feeding, and conditioned place preference. We found that Gq activation of these neurons produce behaviors opposite to what is expected from the LHb as a whole—they decreased anxiety-like and fear behavior and produced a conditioned place preference. In conclusion, PACAP-expressing neurons in LHb represents a molecularly diverse population of cells that oppose the actions of the remainder of LHb neurons by being rewarding or diminishing the negative consequences of aversive events.

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来源期刊
Genes Brain and Behavior
Genes Brain and Behavior 医学-行为科学
CiteScore
6.80
自引率
4.00%
发文量
62
审稿时长
4-8 weeks
期刊介绍: Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes. Genes Brain and Behavior is pleased to offer the following features: 8 issues per year online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions A large and varied editorial board comprising of international specialists.
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