Heat acclimation is an adaptive process that improves physiological performance and supports survival in the face of increasing environmental temperatures, but the underlying mechanisms are not well understood. Here we identified a discrete group of neurons in the mouse hypothalamic preoptic area (POA) that rheostatically increase their activity over the course of heat acclimation, a property required for mice to become heat tolerant. In non-acclimated mice, peripheral thermoafferent pathways via the parabrachial nucleus activate POA neurons and mediate acute heat-defense mechanisms. However, long-term heat exposure promotes the POA neurons to gain intrinsically warm-sensitive activity, independent of thermoafferent parabrachial input. This newly gained cell-autonomous warm sensitivity is required to recruit peripheral heat tolerance mechanisms in acclimated animals. This pacemaker-like, warm-sensitive activity is driven by a combination of increased sodium leak current and enhanced utilization of the Na_V1.3 ion channel. We propose that this salient neuronal plasticity mechanism adaptively drives acclimation to promote heat tolerance.

热驯化是一种适应性过程，可以提高生理机能并支持在面对不断升高的环境温度下的生存，但其潜在机制尚不清楚。在这里，我们在小鼠下丘脑视前区 （POA） 中确定了一组离散的神经元，它们在热驯化过程中以恒流方式增加其活性，这是小鼠变得耐热所必需的特性。在未适应的小鼠中，通过肱旁核的外周热传入通路激活 POA 神经元并介导急性热防御机制。然而，长期热暴露会促进 POA 神经元获得本质上的热敏感活动，而与热传入臂旁输入无关。这种新获得的细胞自主温暖敏感性是招募驯化动物的外周耐热机制所必需的。这种类似起搏器的温敏感活性是由钠泄漏电流增加和 Na_V1.3 离子通道利用率增强共同驱动的。我们提出这种显着的神经元可塑性机制适应性地驱动驯化以促进耐热性。