Investigating a role for dopamine in organizing behavioral sequencing

研究多巴胺在组织行为排序中的作用

• 批准号: 10380483
• 负责人: Maya Jay
• 金额: $ 4.03万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2025-05-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10380483
• 关键词: Algorithms; Animal Behavior; Animals; Axon; Basal Ganglia; Behavior; Behavioral; Brain; Characteristics; Chronic; Corpus striatum structure; Data; Decision Making; Dopamine; Dopamine Receptor; Entropy; Environment; Image; Individual; Learning; Mediating; Midbrain structure; Motion; Motor; Movement; Mus; Neurotransmitters; Organism; Pattern; Peptide Signal Sequences; Phase; Probability; Psychological reinforcement; Role; Series; Stereotyping; Structure; Testing; Time; Variant; Work; base; behavioral construct; dopaminergic neuron; experimental study; flexibility; machine vision; motor control; neurotransmitter release; phase change; prevent; relating to nervous system; stereotypy; Algorithms; Animal Behavior; Animals; Axon; Basal Ganglia; Behavior; Behavioral; Brain; Characteristics; Chronic; Corpus striatum structure; Data; Decision Making; Dopamine; Dopamine Receptor; Entropy; Environment; Image; Individual; Learning; Mediating; Midbrain structure; Motion; Motor; Movement; Mus; Neurotransmitters; Organism; Pattern; Peptide Signal Sequences; Phase; Probability; Psychological reinforcement; Role; Series; Stereotyping; Structure; Testing; Time; Variant; Work; base; behavioral construct; dopaminergic neuron; experimental study; flexibility; machine vision; motor control; neurotransmitter release; phase change; prevent; relating to nervous system; stereotypy

Abstract The brain assesses the environment, makes decisions, and turns decisions into behavior. Behavior, or the total outward movement displayed by an organism, is constructed by stitching together small, stereotyped bits of movement, or ‘syllables’ of action. The complexity of innate animal behavior is in part derived from the fact that the dozens or hundreds of syllables that an animal can perform can be flexibly concatenated into a nearly infinite variety of syllable sequences. Some sequences are deterministic — with syllable B always following syllable A in time — while others are constructed more probabilistically. Escape behaviors, for example, are typically more determined, while foraging is composed in a more probabilistic manner. In the mammalian brain, the dorsolateral striatum (DLS) is responsible for concatenating syllables into sequences of behavior, but it is unclear is how the DLS strings actions together into either variable or stereotyped sequences. One hypothesis is that the release of the neurotransmitter dopamine in DLS is capable of carrying information about – and perhaps regulates – how the DLS chooses to construct behavioral sequences. However, testing this hypothesis requires developing a quantitative description of how continuous behavior is segmented into discrete syllable movements. Recent work in our lab has developed an algorithm called Motion Sequencing, or ‘MoSeq’ for short, which objectively and automatically segments mouse behavior into its component syllables. Since MoSeq affords us fine-timescale information regarding the identity of each syllable and the temporal boundaries between one syllable and the next, we can now explore how dopamine activity in the DLS relates to the sequence structure of ongoing mouse behavior. Here, I propose to combine the MoSeq’s segmentation pipeline with neural imaging and manipulation approaches to investigate the relationship between striatal dopamine and behavioral sequence variability. Based upon preliminary data, I hypothesize that high levels of dopamine release both predicts the expression of variable sequences, and causally influences sequence variability during spontaneous behavior. In Aim 1, I will simultaneously perform recordings of dopamine release in DLS and MoSeq behavioral recordings; I will investigate how syllable-associated dopamine relates to the variability of the behavioral sequence in which a syllable is embedded. In Aim 2, I will leverage a real-time variant of the MoSeq platform, in which a syllable can be detected as an animal is performing it. I will stimulate DLS-projecting dopaminergic axons during the expression of specific target syllables and examine changes in the variability of syllables that follow the target. These experiments will reveal fast-timescale relationships between striatal dopamine and behavioral sequences and will advance our understanding of how animals are able to flexibly construct sequences of syllables on a moment-to-moment basis.

抽象的 大脑评估环境，做出决策，并将决策变成行为。行为或总数 由生物体展示的向外运动，是通过将小小的定型观念缝合在一起来构建的 动作或行动的“ sylables”。先天动物行为的复杂性部分源于以下事实 动物可以执行的数十个或数百个音节可以灵活地连接到几乎无限 多种音节序列。某些序列是确定性的 - 音节B始终遵循音节A 及时 - 而其他人则更可能是更多的。例如，逃脱行为通常更多 确定觅食是以更概率的方式组成的。在哺乳动物大脑中，背外侧 纹状体（DLS）负责将sylable串联为行为序列，但目前尚不清楚如何 DLS字符串将作用共同成分变量或刻板印象序列。一个假设是释放 DLS中的神经递质多巴胺能够携带有关以及调节的信息 DLS选择构建行为序列。但是，检验该假设需要开发 定量描述如何将连续行为细分为离散的音节运动。最近的工作 在我们的实验室中 将鼠标行为自动将其组成的音节段。由于Moseq为我们提供了微观的时间 有关每个音节标识的信息以及一个音节和一个音节之间的临时界限 接下来，我们可以探索DLS中的多巴胺活性如何与正在进行的鼠标的序列结构相关 行为。在这里，我建议将Moseq的分割管道与神经成像和操纵相结合 研究纹状体多巴胺与行为序列变异性之间关系的方法。基于 根据初步数据，我假设高水平的多巴胺释放都预测了 可变序列以及因果关系会影响赞助行为期间的序列变异性。目标 1，我只需在DLS和Moseq行为记录中执行多巴胺释放的记录；我会 研究音节相关的多巴胺如何与行为序列的变异性相关联 Sylable嵌入。在AIM 2中，我将利用Moseq平台的实时变体，其中Sylable CAN可以 被检测为动物正在执行它。我将在刺激DLS投射多巴胺能轴突 表达特定目标音节的表达并检查遵循目标音节变异性的变化。 这些实验将揭示纹状体多巴胺与行为序列之间的快速尺度关系 并将促进我们对动物如何灵活构建音节序列的理解 瞬间的矩。