Carter Matthew E, Han Sung, Palmiter Richard D
Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, Washington 98195.
Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, Washington 98195
J Neurosci. 2015 Mar 18;35(11):4582-6. doi: 10.1523/JNEUROSCI.3729-14.2015.
Conditioned taste aversion (CTA) is a phenomenon in which an individual forms an association between a novel tastant and toxin-induced gastrointestinal malaise. Previous studies showed that the parabrachial nucleus (PBN) contains neurons that are necessary for the acquisition of CTA, but the specific neuronal populations involved are unknown. Previously, we identified calcitonin gene-related peptide (CGRP)-expressing neurons in the external lateral subdivision of the PBN (PBel) as being sufficient to suppress appetite and necessary for the anorexigenic effects of appetite-suppressing substances including lithium chloride (LiCl), a compound often used to induce CTA. Here, we test the hypothesis that PBel CGRP neurons are sufficient and necessary for CTA acquisition in mice. We show that optogenetic activation of these neurons is sufficient to induce CTA in the absence of anorexigenic substances, whereas genetically induced silencing of these neurons attenuates acquisition of CTA upon exposure to LiCl. Together, these results demonstrate that PBel CGRP neurons mediate a gastrointestinal distress signal required to establish CTA.
条件性味觉厌恶(CTA)是一种个体在新味觉刺激与毒素诱发的胃肠道不适之间形成关联的现象。先前的研究表明,臂旁核(PBN)含有对CTA习得所必需的神经元,但具体涉及的神经元群体尚不清楚。此前,我们已确定PBN外侧外部亚区(PBel)中表达降钙素基因相关肽(CGRP)的神经元足以抑制食欲,并且对于包括氯化锂(LiCl)在内的食欲抑制物质的厌食作用是必需的,氯化锂是一种常用于诱发CTA的化合物。在此,我们检验了PBel CGRP神经元对小鼠CTA习得既充分又必要的假设。我们发现,在不存在厌食物质的情况下,这些神经元的光遗传学激活足以诱发CTA,而对这些神经元进行基因诱导沉默会减弱暴露于LiCl时CTA的习得。总之,这些结果表明,PBel CGRP神经元介导了建立CTA所需的胃肠道不适信号。