Lemon Christian H, Li Jinrong, Ali Md Sams Sazzad, Ngum Neville M, Zumpano Kyle T, Roberts Catori J
School of Biological Sciences, University of Oklahoma, Norman, Oklahoma 73019
School of Biological Sciences, University of Oklahoma, Norman, Oklahoma 73019.
eNeuro. 2025 Oct 7;12(10). doi: 10.1523/ENEURO.0191-25.2025. Print 2025 Oct.
The parabrachial (PB) nucleus participates in taste processing and integration with other senses. PB neurons that express the gene support sensory-integrative responses, albeit only limited data have addressed their influence on taste. Here we investigated how chemogenetic dampening of PB- neurons affected mouse orosensory preferences for diverse taste stimuli in brief-access fluid exposure tests, which capture oral sensory/tongue control of licking behavior. Intracranial delivery of Cre-dependent viruses in female and male mice induced expression of the inhibitory designer receptor hM4Di:mCherry (hM4Di mice) or fluorophore mCherry alone (mCherry control mice) in PB- neurons. Several weeks later, hM4Di and mCherry mice entered brief-access tests where they could lick solutions during discrete, seconds-long trials. Stimuli included concentration series of the behaviorally avoided bitter taste stimuli quinine and cycloheximide, the appetitive sugar sucrose, and mildly cool water and less preferred innocuous warm water. Blinded experimenters administered the hM4Di ligand clozapine--oxide (CNO) to all hM4Di and mCherry mice prior to daily tests. With CNO, hM4Di mice displayed greater average licking (i.e., less avoidance) of quinine than mCherry mice ( < 0.05). Moreover, male hM4Di mice selectively showed reduced mean licking preferences for sucrose under CNO ( < 0.05). These data suggest that PB- neurons participate in both aversive and appetitive taste-guided behaviors, with their role in appetitive taste dependent on sex. Finally, orosensory responses to cycloheximide and thermal-controlled water did not differ ( > 0.05) between hM4Di and mCherry mice under CNO. Results are discussed considering functional differences among stimuli and study limitations.
臂旁核（PB）参与味觉处理以及与其他感觉的整合。表达该基因的PB神经元支持感觉整合反应，尽管仅有有限的数据涉及其对味觉的影响。在此，我们在短暂接触液体暴露试验中研究了PB神经元的化学遗传学抑制如何影响小鼠对多种味觉刺激的口面部感觉偏好，该试验可捕捉舔舐行为的口腔感觉/舌头控制。在雌性和雄性小鼠的颅内注射依赖于Cre的病毒，可诱导在PB神经元中表达抑制性设计受体hM4Di：mCherry（hM4Di小鼠）或单独的荧光团mCherry（mCherry对照小鼠）。几周后，hM4Di和mCherry小鼠进入短暂接触试验，在离散的、持续数秒的试验中它们可以舔舐溶液。刺激物包括行为上回避的苦味刺激物奎宁和环己酰亚胺的浓度系列、开胃糖蔗糖、微冷水和较不喜欢的无害温水。在每日测试前，不知情的实验人员给所有hM4Di和mCherry小鼠施用hM4Di配体氯氮平-N-氧化物（CNO）。使用CNO时，hM4Di小鼠对奎宁的平均舔舐次数比mCherry小鼠更多（即回避更少）（P<0.05）。此外，雄性hM4Di小鼠在CNO作用下对蔗糖的平均舔舐偏好选择性降低（P<0.05）。这些数据表明，PB神经元参与厌恶和开胃味觉引导行为，其在开胃味觉中的作用取决于性别。最后，在CNO作用下，hM4Di和mCherry小鼠对环己酰亚胺和温度控制水的口面部反应没有差异（P>0.05）。结合刺激物之间的功能差异和研究局限性对结果进行了讨论。
