Relaxin family peptide receptor 3 (RXFP3) expressing cells in the zona incerta/lateral hypothalamus augment behavioural arousal.

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Neurochemistry Pub Date : 2024-09-04 DOI:10.1111/jnc.16217
Brandon K Richards, Sarah S Ch'ng, Ariel B Simon, Terence Y Pang, Jee Hyun Kim, Andrew J Lawrence, Christina J Perry
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Abstract

Fear-related psychopathologies, such as post-traumatic stress disorder, are linked to dysfunction in neural circuits that govern fear memory and arousal. The lateral hypothalamus (LH) and zona incerta (ZI) regulate fear, but our understanding of the precise neural circuits and cell types involved remains limited. Here, we examined the role of relaxin family peptide receptor 3 (RXFP3) expressing cells in the LH/ZI in conditioned fear expression and general arousal in male RXFP3-Cre mice. We found that LH/ZI RXFP3+ (LH/ZIRXFP3) cells projected strongly to fear learning, stress, and arousal centres, notably, the periaqueductal grey, lateral habenula, and nucleus reuniens. These cells do not express hypocretin/orexin or melanin-concentrating hormone but display putative efferent connectivity with LH hypocretin/orexin+ neurons and dopaminergic A13 cells. Following Pavlovian fear conditioning, chemogenetically activating LH/ZIRXFP3 cells reduced fear expression (freezing) overall but also induced jumping behaviour and increased locomotor activity. Therefore, the decreased freezing was more likely to reflect enhanced arousal rather than reduced fear. Indeed, stimulating these cells produced distinct patterns of coactivation between several motor, stress, and arousal regions, as measured by Fos expression. These results suggest that activating LH/ZIRXFP3 cells generates brain-wide activation patterns that augment behavioural arousal.

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下丘脑内侧带/外侧的松弛素家族肽受体3(RXFP3)表达细胞可增强行为唤醒。
与恐惧有关的精神病理学,如创伤后应激障碍,与支配恐惧记忆和唤醒的神经回路功能障碍有关。外侧下丘脑(LH)和内侧下丘脑(ZI)调节恐惧,但我们对其中涉及的精确神经回路和细胞类型的了解仍然有限。在这里,我们研究了雄性 RXFP3-Cre 小鼠 LH/ZI 中表达弛缓素家族肽受体 3(RXFP3)的细胞在条件性恐惧表达和一般唤醒中的作用。我们发现,LH/ZI RXFP3+(LH/ZIRXFP3)细胞强烈投射到恐惧学习、应激和唤醒中枢,尤其是咽周灰质、外侧哈文脑和团圆核。这些细胞不表达视网膜下素/视网膜素或黑色素浓缩激素,但显示出与LH视网膜下素/视网膜素+神经元和多巴胺能A13细胞的传出连接。在巴甫洛夫恐惧条件反射后,化学激活 LH/ZIRXFP3 细胞可减少恐惧表达(冻结),但也可诱导跳跃行为和增加运动活动。因此,冻结的减少更有可能反映了唤醒的增强,而不是恐惧的减少。事实上,刺激这些细胞会在多个运动、应激和唤醒区域之间产生不同的共激活模式,这是由 Fos 表达所衡量的。这些结果表明,激活LH/ZIRXFP3细胞可产生全脑激活模式,从而增强行为唤醒。
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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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