Activation of Lateral Parabrachial Nucleus (LPBn) PACAP-Expressing Projection Neurons to the Bed Nucleus of the Stria Terminalis (BNST) Enhances Anxiety-like Behavior.
Activation of Lateral Parabrachial Nucleus (LPBn) PACAP-Expressing Projection Neurons to the Bed Nucleus of the Stria Terminalis (BNST) Enhances Anxiety-like Behavior.
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DOI：
10.1007/s12031-021-01946-z
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Hammack SE
中科院分区：
文献类型：
--
作者：
Boucher MN;Aktar M;Braas KM;May V;Hammack SE
焦虑症是最常见的精神疾病之一，了解焦虑和压力相关行为的潜在神经回路可能对治疗很重要。终纹床核（BNST）已被研究其在许多应激相关病理学中的作用，如焦虑、疼痛、抑郁和成瘾。我们先前的工作已经证明，垂体腺苷酸环化酶激活多肽（PACAP）受体激活的BNST介导的慢性应激的许多行为后果。虽然BNST含有局部PACAP表达神经元，但传入PACAP的主要来源是臂旁外侧核（LPBn），并且LPBn的兴奋性毒性病变显著降低了BNST中的PACAP免疫染色。在这里，我们首先通过将AAV 2-hSyn-DIO-mCherry注射到PACAP-IRES-Cre小鼠的LPBn中进行回路映射研究来评估Cre依赖性报告基因表达，并鉴定了PACAP向BNST、杏仁核外侧囊中央核（CeLC）和下丘脑腹内侧核（VMH）的投射。在第二项研究中，我们通过将AAV 2-hSyn-DIO-hM 3D（Gq）-mCherry注射到PACAP-IRES-Cre小鼠的LPBn中来评估BNST中化学发生激活LPBn PACAP传入的作用，以用于仅由设计药物激活的兴奋性设计受体（DREADD）的Cre依赖性表达。在行为测试之前，将我们的DREADD的选择性激动剂氯氮平-N-氧化物（CNO）直接注入BNST。我们发现，在BNST中特异性激活LPBn PACAP传入后，与对照组相比，小鼠的焦虑样行为增加，而总的运动活动不受影响。这些结果表明，激活PACA Pergic LPBn投射到BNST可能在产生焦虑样行为中起重要作用。
Anxiety disorders are among the most common psychiatric disorders, and understanding the underlying neurocircuitry of anxiety- and stress-related behaviors may be important for treatment. The bed nucleus of the stria terminalis (BNST) has been studied for its role in many stress-related pathologies, such as anxiety, pain, depression, and addiction. Our prior work has demonstrated that pituitary adenylate cyclase-activating polypeptide (PACAP) receptor activation in the BNST mediates many of the behavioral consequences of chronic stress. While the BNST contains local PACAP-expressing neurons, a major source of afferent PACAP is the lateral parabrachial nucleus (LPBn), and excitotoxic lesions of the LPBn substantially decreasess PACAP immunostaining in the BNST. Here, we first assessed Cre-dependent reporter expression by injecting AAV2-hSyn-DIO-mCherry into the LPBn of PACAP-IRES-Cre mice for circuit mapping studies and identified PACAP projections to the BNST, lateral capsular central nucleus of the amygdala (CeLC), and ventromedial hypothalamus (VMH). In a second study, we assessed the effects of chemogenetically activating LPBn PACAP afferents in the BNST by injecting AAV2-hSyn-DIO-hM3D(Gq)-mCherry into the LPBn of PACAP-IRES-Cre mice for Cre-dependent expression of excitatory designer receptors exclusively activated by designer drugs (DREADDs). Before behavioral testing, clozapine-N-oxide (CNO), the selective agonist of our DREADD, was infused directly into the BNST. We found that after specific activation of LPBn PACAP afferents in the BNST, mice had increased anxiety-like behavior compared with controls, while total locomotor activity was unaffected. These results indicate that activation of PACAPergic LPBn projections to the BNST may play an important role in producing anxiety-like behavior.
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DOI：
10.1152/ajpgi.00501.2011
发表时间：
2012-06-01
影响因子：
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