Principles of sensorimotor processing in zebrafish thermosensation

斑马鱼热感觉的感觉运动处理原理

• 批准号: 10300619
• 负责人: Martin Haesemeyer
• 金额: $ 38.65万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10300619
• 关键词: Ablation; Adaptive Behaviors; Algorithms; Anatomy; Animals; Behavior; Behavioral; Biophysical Process; Biophysics; Brain; Brain Stem; Calcium; Cells; Data; Detection; Disease; Electrophysiology (science); Electroporation; Encapsulated; Environment; Generations; Goals; Health; Heating; Image; Label; Maps; Modality; Modeling; Motor output; Nervous system structure; Neural Network Simulation; Neurons; Neurosciences; Optics; Output; Physiologic Thermoregulation; Physiology; Property; Research; Resolution; Role; Sensory; Shapes; Stimulus; Study models; Techniques; Temperature; Testing; Time; Trigeminal System; Vision; Work; Zebrafish; base; behavioral response; biophysical model; cell type; experimental study; heat stimulus; hindbrain; image guided; insight; motor control; multi-scale modeling; nervous system disorder; neural circuit; novel; patch clamp; predictive modeling; relating to nervous system; response; sensory input; sensory stimulus; two-photon

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.

概括 我们的长期目标是理解上下文中感觉运动转换的计算 的体温调节行为。响应感官刺激而产生适当的行为对于 任何动物的生存。斑马鱼幼体将用于这些研究，因为它是唯一的脊椎动物模型 它可以全面识别和操纵温度调节电路。重要的是，幼虫 斑马鱼是变温动物，因此完全依赖热梯度导航 体温调节。这意味着底层的感觉运动转换是稳健的，因为准确 体温调节对于生存至关重要。 斑马鱼神经系统对神经活动的光学记录的可及性使我们能够绘制地图 首次在动物中建立从感觉输入到行为输出的温度调节回路。这项研究 确定了两类关键的后脑神经元，它们编码加热速率和冷却速率 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的 三叉神经感觉输入。该提案的目的是揭示这些的生物物理机制 计算及其在行为生成中的作用，以生成感觉运动的多尺度模型 转变。所提出的实验以有关后脑计算的可检验假设为指导 这是基于我们之前的电路建模工作。具体来说，该研究将调查 (1) 细胞 计算加热和冷却响应的机制，(2) 电路解剖结构如何支持这一点 计算以及（3）加热和冷却神经元的反应如何影响转动过程中的转动 体温调节行为。为此，实验将在功能上结合（1）贴片电生理学 识别神经元，（2）通过电穿孔进行单细胞标记，（3）随后进行细胞类型特异性消融 通过行为记录。 这项研究将填补我们对感觉运动转换理解的一个关键空白：如何计算 从细胞特性到电路，不同尺度相互作用，产生适应性行为，以响应 感官刺激。对感觉运动转换的保守原理和发散原理的理解 跨动物和感觉方式的研究还有望深入了解神经系统中出现的问题 疾病表明感觉处理出现问题。