Circuits for spontaneous behavior and phototaxis in a simple model chordate

简单脊索动物模型中自发行为和趋光性的电路

• 批准号: 10446697
• 负责人: William Smith
• 金额: $ 66.48万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10446697
• 关键词: 3-Dimensional; Ablation; Address; Anatomy; Animals; Anterior; Automobile Driving; Behavior; Brain; Brain region; Cells; Chordata; Complement; Complex; Cues; Data; Development; Embryo; Environment; Frequencies; Human; Individual; Interneurons; Larva; Lasers; Lead; Light; Lighting; Link; Location; Modeling; Movement; Names; Nervous system structure; Neurons; Pattern; Periodicity; Pharmacology Study; Phase; Photoreceptors; Picrotoxin; Positioning Attribute; Property; Regulator Genes; Regulatory Element; Research Personnel; Role; Source; Swimming; Synapses; Tail; Testing; Trees; Urochordata; Vertebrates; Vesicle; base; behavioral outcome; cholinergic; cholinergic neuron; connectome; experimental study; falls; gamma-Aminobutyric Acid; inhibitor; insight; large datasets; mutant; neural circuit; neural model; optogenetics; time interval; tool

This proposal will investigate neural circuits driving negative phototaxis in an emerging model for neural circuit analysis: larvae of the primitive chordate Ciona. Ciona larvae have a number of features that make them ideally suited for this project. They are small and transparent, and have only 177 CNS neurons. Moreover, putative circuits for phototaxis have been identified from the Ciona connectome. Negative phototaxis in Ciona larvae consists of two phases. First, the larvae perform short orienting swims in which they attempt to discern the direction of ambient lighting by moving their bodies. Second, if the larva detects a change in light falling on their photoreceptors as they turn away from the light source, a sustained negative phototactic swim results. However, many orienting swims terminate without a sustained swim. This proposal will examine two aspects of phototaxis: 1) how neural circuits regulate the frequency of orienting swims; and 2) how orienting and sustained swims are linked at the circuit level. Ciona larvae show a wide distribution in the time intervals between short orienting swims. However, analysis of a large dataset of swim interval times points to underlying oscillations governing spontaneous swims frequency, with the dominant period being once every two seconds (O.5 Hz). In preliminary studies we have identified a VGAT-positive neuron that oscillates with a frequency of 0.5 Hz in a region of Ciona CNS called the anterior brain vesicle. We have named the oscillating neuron the anterior brain vesicle oscillator (aBVO). Moreover, mutant and pharmacological studies both point to the aBVO as a likely regulator of spontaneous swim frequency. Proposed experiments in Specific Aim 1 will target the aBVO neuron using optogenetic tools and laser ablation, and then assess the behavioral outcomes. Specific Aim 2 will address the second question: what is the circuit link between short spontaneous orienting and sustained phototactic swims? Our preliminary studies recording GCaMP activity in VACHT-positive neurons suggest a plausible and testable circuit model. We observed that short spontaneous tail movements in larvae were accompanied by Ca2+ transients in the same VACHT-positive interneurons that are the primary targets of the photoreceptors - a neuron class called photoreceptor relay neurons (prRNs). Moreover, the connectome allowed us to identify likely candidate neurons corresponding to the aBVO, based on their 3D locations and connectivities, and the major synaptic targets of these candidate neurons are also the prRNs. Thus, we hypothesize that short orienting swims are initiated in the same circuit as the sustained phototactic swims, and it is the presence or absence of input from the photoreceptors that determines if a sustained swim is initiated. Experiments in Specific Aim 2 will test this hypothesis by targeting the prRNs to determine if they are necessary for the initiation of orienting swims. We also hypothesize that in the absence of aBVO inhibition the prRNs would oscillate. We will test this hypothesis by examining a mutant line that lacks the aBV region of the CNS.

本计画将在一个新兴的神经回路模型中探讨驱动负趋光性的神经回路 分析：原始脊索动物玻璃海鞘的幼虫。玻璃海鞘幼虫有很多特征 非常适合这个项目。它们很小，透明，只有177个CNS神经元。此外，委员会认为， 已经从玻璃海鞘连接体中鉴定出了推测的趋光性回路。玻璃海鞘的负趋光性 幼虫由两个阶段组成。首先，幼虫进行短暂的定向游泳， 通过移动他们的身体来控制周围光线的方向。第二，如果幼虫察觉到光线的变化， 它们的光感受器在远离光源时，产生持续的负趋光性游泳。 然而，许多定向游泳在没有持续游泳的情况下终止。本提案将审查以下两个方面： 趋光性：1）神经回路如何调节定向游泳的频率; 2）如何定向和 持续的游泳是在电路水平连接。玻璃海鞘幼虫在时间间隔上分布较广 在短暂的定向游泳之间。然而，对游泳间隔时间的大型数据集的分析表明， 控制自发游泳频率的振荡，主导周期为每两秒一次 (O.5 Hz）。在初步研究中，我们已经确定了一个VGAT阳性神经元，其振荡频率为 0.5赫兹在一个区域的玻璃海鞘中枢神经系统称为前脑泡。我们将振荡神经元命名为 前脑囊泡振荡器（aBVO）。此外，突变体和药理学研究都指向aBVO 可能是自发游泳频率的调节器。具体目标1中拟议的实验将针对 aBVO神经元使用光遗传学工具和激光消融，然后评估行为结果。具体 目标2将解决第二个问题：短自发定向和 持续的趋光性游泳我们的初步研究记录GCaMP活性在VACHT阳性神经元 提出了一个合理的和可测试的电路模型。我们观察到幼虫的短的自发尾巴运动 在相同的VACHT阳性中间神经元中伴随着Ca 2+瞬变，这些中间神经元是VACHT的主要靶点。 光感受器-一种称为光感受器中继神经元（prRN）的神经元类别。此外，连接体 使我们能够根据它们的3D位置识别与aBVO对应的可能候选神经元， 连接，并且这些候选神经元的主要突触靶标也是prRN。因此我们 假设短定向游泳是在与持续趋光游泳相同的回路中启动的，并且 来自光感受器的输入的存在或不存在决定持续游泳是否开始。 具体目标2中的实验将通过靶向prRN来测试这一假设，以确定它们是否 这是开始定向游泳所必需的。我们还假设，在没有aBVO抑制的情况下， prRN会振荡。我们将通过检查缺乏aBV区域的突变株来检验这一假设。 CNS。

项目成果

A single oscillating proto-hypothalamic neuron gates taxis behavior in the primitive chordate Ciona.

单个振荡的原下丘脑神经元控制着原始脊索动物海鞘的滑行行为。

• DOI: 10.1101/2023.04.24.538092
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Chung,Janeva;Newman-Smith,Erin;Kourakis,MatthewJ;Miao,Yishen;Borba,Cezar;Medina,Juan;Laurent,Tao;Gallean,Benjamin;Faure,Emmanuel;Smith,WilliamC
• 通讯作者: Smith,WilliamC