雄性小鼠外侧视前核神经元的不同群体通过不同的投射共同促成了类似抑郁的行为

IF 4.3 2区 医学 Q1 NEUROSCIENCES
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引用次数: 0

摘要

外侧视前区(LPO)是下丘脑的一个组成部分,参与睡眠-觉醒转换、体温调节和水盐平衡等多种生理功能。在这项研究中,我们发现LPO的不同兴奋神经元分别投射到厌恶处理中枢外侧哈文脑(LHb)和奖赏处理中枢腹侧被盖区(VTA)。慢性束缚应激(CRS)后,LHb投射和VTA投射的LPO神经元分别表现出神经元活动的增加和减少。光遗传激活LHb投射的LPO兴奋神经元和LHb内的LPO兴奋神经元末梢会诱发小鼠的厌恶和回避行为,而激活VTA投射的LPO兴奋神经元和VTA内的LPO兴奋神经元末梢则会使小鼠产生偏好和探索行为。此外,在CRS期间,无论是光遗传学抑制LHb投射的LPO兴奋神经元,还是激活VTA投射的LPO兴奋神经元,都能有效防止抑郁样行为的发生。我们的研究首次揭示了源自LPO的不同通路,这些通路调控小鼠相反的情感状态,并暗示它们的活动失衡可能导致抑郁样行为。这些回路是缓解神经精神疾病中情感功能障碍的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distinct populations of lateral preoptic nucleus neurons jointly contribute to depressive-like behaviors through divergent projections in male mice

The lateral preoptic area (LPO) is a component of the hypothalamus involved in various physiological functions including sleep-wakefulness transition, thermoregulation, and water-salt balance. In this study, we discovered that distinct LPO excitatory neurons project separately to the aversive processing center lateral habenula (LHb) and the reward processing hub ventral tegmental area (VTA). Following chronic restraint stress (CRS), the LHb-projecting and VTA-projecting LPO neurons exhibited increased and decreased neuronal activities, respectively. Optogenetic activation of LHb-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within LHb evoked aversion and avoidance behaviors, while activation of VTA-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within VTA produced preference and exploratory behaviors in mice. Furthermore, either optogenetic inhibition of LHb-projecting LPO excitatory neurons or activation of VTA-projecting LPO excitatory neurons during CRS effectively prevented the development of depressive-like behaviors. Our study unveils, for the first-time, divergent pathways originating from LPO that regulate opposite affective states in mice and implicates that an imbalance of their activities could lead to depressive-like behaviors. These circuitries represent promising therapeutic targets to relieve emotional dysfunctions in neuropsychiatric disorders.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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