Principles of sensorimotor processing in zebrafish thermosensation

摘要 我们的长期目标是理解在上下文中作为感觉-运动转换基础的计算 体温调节行为。对感官刺激产生适当的行为对于 任何动物的生存。幼虫斑马鱼将用于这些研究，因为它是唯一的脊椎动物模型 其允许全面识别和操纵温度调节电路。重要的是，幼虫 斑马鱼是一种外温性动物，因此完全依靠温度梯度导航 温度调节。这意味着潜在的感觉-运动转换是健壮的，因为 体温调节对生存至关重要。 斑马鱼神经系统对神经活动的光学记录使我们能够 体温调节回路，从感觉输入到行为输出，在任何动物中都是第一次。这项研究 确定了两类关键的后脑神经元，它们编码了大脑的升温速率和冷却速率。 环境。值得注意的是，这些加热和冷却反应是在后脑中从头计算出来的 三叉神经感觉传入。这项提议的目的是揭示这些疾病的生物物理机制。 用于生成感觉-运动多尺度模型的计算及其在行为生成中的作用 变形。建议的实验是由关于后脑计算的可测试假设指导的 这是基于我们之前的电路建模工作。具体地说，这项研究将调查(1)细胞 计算加热和冷却响应的机制，(2)电路解剖学如何支持这一点 计算和(3)加热和冷却神经元的反应如何影响在 体温调节行为。为此，实验将结合(1)功能上的贴片电生理学 识别的神经元，(2)通过电穿孔的单细胞标记，以及(3)随后的特定细胞类型的消融 通过行为记录。 这项研究将填补我们对感觉-运动转换的理解的一个关键空白：计算如何在 不同的尺度，从细胞属性到电路，相互作用以产生适应行为，以响应 感官刺激。对感觉-运动转换的守恒和发散原理的理解 通过动物和感官模式进一步洞察神经学上的错误 感觉处理出现问题的疾病状态。

SUMMARY It is our long-term goal to understand computations that underlie sensori-motor transformations in the context of thermoregulatory behaviors. Generating appropriate behaviors in response to sensory stimuli is critical for the survival of any animal. Larval zebrafish will be used for these studies as it is the only vertebrate model which allows comprehensive identification and manipulation of thermoregulatory circuits. Importantly, larval zebrafish is an ectotherm animal and therefore exclusively relies on thermal gradient navigation for thermoregulation. This means that the underlying sensori-motor transformations are robust since accurate thermoregulation is critical for survival. The accessibility of the zebrafish nervous system to optical recording of neural activity enabled us to map thermoregulatory circuits from sensory input to behavioral output for the first time in any animal. This research identified two critical classes of hindbrain neurons which encode the rate of heating and the rate of cooling in the environment. Notably, these heating and cooling responses are computed de-novo in the hindbrain from sensory trigeminal inputs. The aim of this proposal is to uncover the biophysical mechanism of these computations and their role in behavior generation to generate a multiscale model of sensori-motor transformations. The proposed experiments are guided by testable hypotheses about hindbrain computation that are based on our previous circuit modeling efforts. Specifically, the research will investigate the (1) cellular mechanisms of computing heating and cooling responses, (2) how the circuit anatomy supports this computation and (3) how the responses of Heating and Cooling neurons influence turning during thermoregulatory behavior. To this end experiments will combine (1) patch electrophysiology in functionally identified neurons, (2) single cell labeling through electroporations and (3) cell type specific ablations followed by behavioral recordings. This research will fill a critical gap in our understanding of sensori-motor transformations: How computations at different scales, from cellular properties to circuits, interact to generate adaptive behaviors in response to sensory stimuli. The understanding of conserved and divergent principles of sensori-motor transformations across animals and sensory modalities furthermore promises insight into what goes awry in neurological disease states where sensory processing goes awry.