Identification of conserved circuit logic in temperature navigation behavior in fish and fly

温度影响所有生物体的生理过程。未能评估其价值、价态和变化率可能会产生从组织损伤到整个系统失效的各种后果。因此，大多数生物体都进化出了将体温保持在特定的窄范围内的策略。无论采取何种具体策略，神经系统都在检测温度变化、在动物当前的环境和状态下评估它们以及指导生理和行为变化方面发挥着重要作用。神经系统在不同物种之间的温度调节功能之间的进化关系尚不清楚。通过前一期SPP资助的博士生的工作，我们大大提高了我们对神经系统在体温平衡中的作用的理解，与吸温相比，外体温的作用是什么。通过新的行为分析，我们发现鱼和苍蝇使用非常相似的策略来导航温度梯度，以保持或返回到首选的温度范围(“稳态导航”)。我们进一步证明，鱼类通过连接下丘脑视前区(POA)和大脑区域的神经网络实现体温调节，从而实现空间导航。当温度条件恶化时，POA会驱动重新定向，并将这一信息传递给导航控制缰核(HB)-脚间核(IPN)回路，以指导未来的运动动作。这些结果表明POA通过物种特有的神经网络在体温调节中具有保守的功能。此外，我们认为动态平衡导航起源于一个古老的趋化性导航回路，该回路随后被扩展到服务于其他感觉形式。在下一个资助期，我们希望(I)通过结合体内成像和光遗传操作的最先进水平的体内成像和光遗传操作来确定苍蝇体内POA和HB的功能等价物，(Ii)表征5-羟色胺能信号在鱼类和苍蝇体内稳态导航中的作用(反馈和前馈调节)，以及(Iii)通过改变鱼类和苍蝇的温度设置点，通过发育温度、外源性热原和饥饿状态来解决稳态设定点在触发温度导航中的作用。最后，我们将使用这些新数据来更新和提炼计算电路模型中神经元类型和电路动机的一般和物种特定贡献。总而言之，预期的结果将显示功能相同的大脑区域或神经元如何处理联合稳态需求，以及稳态设定点在触发行为以提高进化中不同物种的生存机会方面发挥了什么作用。

Temperature affects the physiological processes of all organisms. A failure to assess its value, valence, and rate of change can have a variety of consequences from tissue damage to failure of the entire system. Thus, most organisms have evolved strategies to maintain their body temperature within a specific narrow range. Regardless of the specific strategy adopted, the nervous system plays an important role in detecting temperature changes, evaluating them in the current context and state of the animal, and directing both physiological and behavioral changes. The evolutionary relationship between the function of the nervous system in temperature regulation between different species remains unclear. Through the work of a PhD student funded by the previous funding period of this SPP, we have significantly advanced our understanding of the role of the nervous system in temperature homeostasis in ectotherms as compared to endotherms. Through novel behavioral assays, we have found that fish and flies use highly similar strategies to navigate temperature gradients to remain in or return to a preferred temperature range (‘homeostatic navigation’). We further showed that fish achieve thermoregulation through a neural network connecting the preoptic area of the hypothalamus (PoA) to brain areas enabling spatial navigation. PoA drives reorientation when thermal conditions are worsening and conveys this information for instructing future motor actions to the navigation-controlling habenula (Hb) - interpeduncular nucleus (IPN) circuit. These results suggest a conserved function of the PoA in thermoregulation acting through species- specific neural networks. Furthermore, we propose that homeostatic navigation arose from an ancient chemotaxis navigation circuit that was subsequently extended to serve in other sensory modalities. In the next funding period, we want to (i) identify the functional equivalents of the PoA and the Hb in the fly by combining state-of-the-art in vivo imaging and optogenetic manipulation during homeostatic navigation, (ii) characterize the role of serotonergic signaling in homeostatic navigation in fish and fly (feedback and feedforward modulation), and (iii) address the role of homeostatic setpoints in triggering temperature navigation by changing the temperature setpoint of fish and flies though developmental temperature, exogenous pyrogens, and hunger states. Finally, we will use these new data to update and refine the general and species-specific contribution of neuron types and circuit motives in a computational circuit model. Together the expected results will show how joint homeostatic needs are processed by functionally equivalent brain regions or neurons and which role the homeostatic setpoint plays in triggering behavior to improve survival chances of evolutionary distinct species.