Parabrachial Calcitonin Gene-Related Peptide Neurons Mediate Conditioned Taste Aversion

Parabrachial Calcitonin Gene-Related Peptide Neurons Mediate Conditioned Taste Aversion
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DOI:
10.1523/jneurosci.3729-14.2015
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发表时间:
2015-03-18
影响因子:
5.3
通讯作者:
Palmiter, Richard D.
Palmiter, Richard D.
中科院分区:
医学1区
文献类型:
--
作者:
Carter, Matthew E.;Han, Sung;Palmiter, Richard D.

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条件性味觉厌恶(CTA)是个体在新型促味剂和毒素诱导的胃肠道不适之间形成关联的现象。以往的研究表明,臂旁核(PBN)包含的神经元是必要的收购CTA,但具体涉及的神经元群体是未知的。以前,我们确定降钙素基因相关肽(CGRP)表达神经元的外侧细分的PBN(PBel)是足以抑制食欲和必要的食欲抑制物质,包括氯化锂(LiCl),化合物经常用于诱导CTA的促食欲作用。在这里,我们测试的假设,PBel CGRP神经元是足够的和必要的CTA收购小鼠。我们表明,这些神经元的光遗传学激活是足以诱导CTA在缺乏致凋亡物质,而遗传诱导的沉默这些神经元衰减收购CTA后,暴露于氯化锂。总之,这些结果表明,PBel CGRP神经元介导建立CTA所需的胃肠道不适信号。
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.