Parvalbumin Interneurons Determine Emotional Valence Through Modulating Accumbal Output Pathways
Parvalbumin Interneurons Determine Emotional Valence Through Modulating Accumbal Output Pathways
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小清蛋白中间神经元通过调节累积输出通路确定情绪效价
DOI：
10.3389/fnbeh.2019.00110
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发表时间：
2019-05-14
影响因子：
3
通讯作者：
Liu, Xing
中科院分区：
文献类型：
--
作者：
Chen, Xi;Liu, Zhiyuan;Liu, Xing
表达GABA能中间神经元的小清蛋白（PV）为纹状体中的多刺投射神经元（SPN）提供大量GABA来源。然而，PV+中间神经元在腹侧纹状体和情绪状态的SPN调节中的作用在很大程度上是未知的。在这里，我们研究了腹侧纹状体（腹侧）PV+中间神经元的刺激是否会驱动小鼠的情绪效价。我们发现，在条件性位置偏爱（CPP）训练过程中，激活延髓PV+中间神经元诱发位置偏爱，而抑制它们则导致条件性位置厌恶（CPA）。PV+ interneurons在位置调节过程中的激活增加了Fos的表达在SPN的直接途径（dSPNs）和受损的氯化锂诱导的CPA。在间接途径（iSPN）中激活dSPN和SPN分别诱导CPP和CPA;相反，抑制dSPN或iSPN诱导CPA或CPP。此外，激活或抑制钙视黄蛋白表达（CR）GABA能中间神经元不会诱导位置偏爱或厌恶。这些数据表明，PV+中间神经元可以双向确定情绪效价通过其调节的神经元SPN活动和提高的可能性，PV+中间神经元活动的操纵可能有可能改变情绪效价和治疗相关的精神障碍。
Parvalbumin (PV) expressing GABAergic interneurons provide large source of GABA to spiny projection neurons (SPNs) in the striatum. However, the roles of PV+ interneurons in the regulation of SPNs in the ventral striatum and emotional states are largely unknown. Here, we investigated whether stimulation of ventral striatal (accumbal) PV+ interneurons would drive emotional valence in mice. We found that during conditioned place preference (CPP) training, activation of accumbal PV+ interneurons evoked place preference while suppressing them resulted in conditioned place aversion (CPA). Activation of PV+ interneurons during place conditioning increased Fos expression in SPNs in the direct pathway (dSPNs) and impaired lithium chloride-induced CPA. Activation of dSPNs and SPNs in the indirect pathway (iSPNs) induced CPP and CPA, respectively; conversely, suppression of dSPNs or iSPNs induced CPA or CPP. In addition, activation or suppression of calretinin-expressing (CR) GABAergic interneurons did not induce place preference or aversion. These data suggest that PV+ interneurons can bidirectionally determine the emotional valence through their regulation of accumbal SPN activities and raise the possibility that manipulation of PV+ interneuron activity may have the potential to alter emotional valence and treat related mental disorders.