PDF(Pubmed)
Abstract：
Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains unclear. Our recent research has identified a specific subpopulation of choline acetyltransferase (ChAT+) neurons localized in the external lateral portion of parabrachial nucleus (eLPBChAT), which modulates METH primed-reinstatement of conditioned place preference (CPP). Here, the anatomical structures and functional roles of eLPBChAT projections in METH withdrawal anxiety and primed reinstatement were further explored. Methods: In the present study, a multifaceted approach was employed to dissect the LPBChAT+ projections in male mice, including anterograde and retrograde tracing, acetylcholine (Ach) indicator combined with fiber photometry recording, photogenetic and chemogenetic regulation, as well as electrophysiological recording. METH withdrawal anxiety-like behaviors and METH-primed reinstatement of conditioned place preference (CPP) were assessed in male mice. Results: We identified that eLPBChAT send projections to PKCδ-positive (PKCδ+) neurons in lateral portion of central nucleus of amygdala (lCeAPKCδ) and oval portion of bed nucleus of the stria terminalis (ovBNSTPKCδ), forming eLPBChAT-lCeAPKCδ and eLPBChAT-ovBNSTPKCδ pathways. At least in part, the eLPBChAT neurons positively innervate lCeAPKCδ neurons and ovBNSTPKCδ neurons through regulating synaptic elements of presynaptic Ach release and postsynaptic nicotinic acetylcholine receptors (nAChRs). METH withdrawal anxiety and METH-primed reinstatement of CPP respectively recruit eLPBChAT-lCeAPKCδ pathway and eLPBChAT-ovBNSTPKCδ pathway in male mice. Conclusion: Our findings put new insights into the complex neural networks, especially focusing on the eLPBChAT projections. The eLPBChAT is a critical node in the neural networks governing METH withdrawal anxiety and primed-reinstatement of CPP through its projections to the lCeAPKCδ and ovBNSTPKCδ, respectively.
摘要：
甲基苯丙胺（METH）戒断焦虑症状和复发一直是临床实践的重大挑战，然而,潜在的神经元基础仍不清楚。我们最近的研究已经确定了位于臂旁核（eLPBChAT）外侧部分的胆碱乙酰转移酶（ChAT）神经元的特定亚群，调节METH启动条件位置偏好(CPP)的恢复。这里,进一步探讨了eLPBChAT投射在METH戒断焦虑和预恢复中的解剖结构和功能作用。方法：在本研究中，采用多方面的方法解剖雄性小鼠的LPBChAT+投影，包括顺行和逆行追踪，乙酰胆碱（Ach）指示剂结合纤维测光记录，光遗传和化学遗传调控，以及电生理记录。在雄性小鼠中评估了METH戒断焦虑样行为和METH引发的条件性位置偏爱（CPP）的恢复。结果：我们发现eLPBChAT将投影发送到杏仁核中央核外侧部分（lCeAPKCδ）和终末纹床核椭圆形部分（ovBNSTPKCδ）的PKCδ阳性（PKCδ）神经元，形成eLPBChAT-lCeAPKCδ和eLPBChAT-ovBNSTPKCδ途径。至少在某种程度上,eLPBChAT神经元通过调节突触前Ach释放和突触后烟碱乙酰胆碱受体（nAChRs）的突触元件，正向神经支配lCeAPKCδ神经元和ovBNSTPKCδ神经元。METH戒断焦虑和METH引发的CPP恢复分别在雄性小鼠中招募eLPBChAT-lCeAPKCδ途径和eLPBChAT-ovBNSTPKCδ途径。结论：我们的发现为复杂的神经网络提供了新的见解，特别是关注eLPBChAT预测。eLPBChAT是神经网络中的关键节点，通过对lCeAPKCδ和ovBNSTPKCδ的预测来控制METH戒断焦虑和CPP的启动恢复，分别。
