Park Gha Yeon, Lee Geehyun, Yoon Jongmin, Han Jisoo, Choi Pyonggang, Kim Minjae, Lee Sungho, Park Chaeri, Wu Zhaofa, Li Yulong, Choi Myunghwan
School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea; The Institute of Molecular Biology and Genetics, Seoul 08826, Republic of Korea.
Korea Brain Research Institute, Daegu 41062, Republic of Korea.
Cell. 2025 Jan 9;188(1):141-156.e16. doi: 10.1016/j.cell.2024.10.041. Epub 2024 Nov 18.
The sense of taste generally shows diminishing sensitivity to prolonged sweet stimuli, referred to as sweet adaptation. Yet, its mechanistic landscape remains incomplete. Here, we report that glia-like type I cells provide a distinct mode of sweet adaptation via intercellular crosstalk with chemosensory type II cells. Using the microfluidic-based intravital tongue imaging system, we found that sweet adaptation is facilitated along the synaptic transduction from type II cells to gustatory afferent nerves, while type I cells display temporally delayed and prolonged activities. We identified that type I cells receive purinergic input from adjacent type II cells via P2RY2 and provide inhibitory feedback to the synaptic transduction of sweet taste. Aligning with our cellular-level findings, purinergic activation of type I cells attenuated sweet licking behavior, and P2RY2 knockout mice showed decelerated adaptation behavior. Our study highlights a veiled intercellular mode of sweet adaptation, potentially contributing to the efficient encoding of prolonged sweetness.
味觉通常对长时间的甜味刺激表现出敏感性降低，这被称为甜味适应。然而，其机制图景仍不完整。在这里，我们报告胶质样I型细胞通过与化学感受性II型细胞的细胞间串扰提供了一种独特的甜味适应模式。使用基于微流控的活体舌成像系统，我们发现沿着从II型细胞到味觉传入神经的突触转导，甜味适应得到促进，而I型细胞表现出时间延迟和延长的活动。我们确定I型细胞通过P2RY2从相邻的II型细胞接收嘌呤能输入，并对甜味的突触转导提供抑制性反馈。与我们在细胞水平上的发现一致，I型细胞的嘌呤能激活减弱了甜味舔舐行为，并且P2RY2基因敲除小鼠表现出适应行为减慢。我们的研究突出了一种隐藏的甜味适应细胞间模式，可能有助于对长时间甜味的有效编码。
