Neural coding of binary mixtures in a structurally related odorant pair.

The encoding of odorant mixtures by olfactory sensory neurons depends on molecular interactions at peripheral receptors. However, the pharmacological basis of these interactions is not well defined. Both competitive and noncompetitive mechanisms of receptor binding and activation, or suppression, could contribute to coding. We studied this by analyzing responses of olfactory bulb glomeruli evoked by a pair of structurally related odorants, eugenol (EG) and methyl isoeugenol (MIEG). Fluorescence imaging in synaptopHluorin (spH) mice revealed that EG and MIEG evoked highly overlapped glomerular inputs, increasing the likelihood of mixture interactions. Glomerular responses to binary mixtures of EG and MIEG mostly showed hypoadditive interactions at intermediate and high odorant concentrations, with a few near threshold responses showing hyperadditivity. Dose-response profiles were well fitted by a model of two odorants competitively binding and activating a shared receptor linked to a non-linear transduction cascade. We saw no evidence of non-competitive mechanisms.

嗅觉感觉神经元对气味混合物的编码取决于外周受体上的分子相互作用。然而，这些相互作用的药理学基础尚未明确界定。受体结合、激活或抑制的竞争性和非竞争性机制都可能有助于编码。我们通过分析一对结构相关的气味物质丁香酚（EG）和甲基异丁香酚（MIEG）诱发的嗅球 glomeruli（肾小球状结构，此处指嗅球中的类似结构）的反应来研究这一问题。在synaptopHluorin（spH）小鼠中的荧光成像显示，EG和MIEG诱发了高度重叠的肾小球状结构输入，增加了混合物相互作用的可能性。对EG和MIEG二元混合物的肾小球状结构反应在中等和高气味物质浓度下大多表现出亚加性相互作用，少数接近阈值的反应表现出超加性。剂量 - 反应曲线通过一个两种气味物质竞争性结合并激活与非线性转导级联相关的共享受体的模型得到了很好的拟合。我们没有发现非竞争性机制的证据。