Department of Physics, Yale University, New Haven, CT 06511.
Quantitative Biology Institute, Yale University, New Haven, CT 06511.
Proc Natl Acad Sci U S A. 2024 Feb 6;121(6):e2308215121. doi: 10.1073/pnas.2308215121. Epub 2024 Jan 31.
In various biological systems, information from many noisy molecular receptors must be integrated into a collective response. A striking example is the thermal imaging organ of pit vipers. Single nerve fibers in the organ reliably respond to milli-Kelvin (mK) temperature increases, a thousand times more sensitive than their molecular sensors, thermo-transient receptor potential (TRP) ion channels. Here, we propose a mechanism for the integration of this molecular information. In our model, amplification arises due to proximity to a dynamical bifurcation, separating a regime with frequent and regular action potentials (APs), from a regime where APs are irregular and infrequent. Near the transition, AP frequency can have an extremely sharp dependence on temperature, naturally accounting for the thousand-fold amplification. Furthermore, close to the bifurcation, most of the information about temperature available in the TRP channels' kinetics can be read out from the times between consecutive APs even in the presence of readout noise. A key model prediction is that the coefficient of variation in the distribution of interspike times decreases with AP frequency, and quantitative comparison with experiments indeed suggests that nerve fibers of snakes are located very close to the bifurcation. While proximity to such bifurcation points typically requires fine-tuning of parameters, we propose that having feedback act from the order parameter (AP frequency) onto the control parameter robustly maintains the system in the vicinity of the bifurcation. This robustness suggests that similar feedback mechanisms might be found in other sensory systems which also need to detect tiny signals in a varying environment.
在各种生物系统中，来自许多嘈杂分子受体的信息必须整合为集体反应。一个引人注目的例子是响尾蛇的热成像器官。器官中的单个神经纤维可靠地响应毫开尔文（mK）的温度升高，比其分子传感器——瞬态受体电位（TRP）离子通道灵敏一千倍。在这里，我们提出了一种整合这种分子信息的机制。在我们的模型中，由于接近动态分岔，放大作用产生，该分岔将频繁和规则动作电位（AP）的区域与 AP 不规则且不频繁的区域分开。在过渡附近，AP 频率对温度的依赖性非常陡峭，自然可以解释一千倍的放大。此外，在分岔附近，即使存在读出噪声，也可以从连续 AP 之间的时间读取 TRP 通道动力学中关于温度的大部分信息。一个关键的模型预测是，在 AP 频率下，尖峰间时间分布的变异系数减小，与实验的定量比较确实表明，蛇的神经纤维非常接近分岔点。虽然接近这样的分岔点通常需要参数的微调，但我们提出，从动作电位频率（AP 频率）反馈到控制参数，会从强有力地保持系统接近分岔点。这种稳健性表明，类似的反馈机制可能存在于其他需要在变化的环境中检测微小信号的感觉系统中。
