Neuroplasticity in chemosensory-mediated social behaviors

化学感应介导的社会行为中的神经可塑性

• 批准号: 10584828
• 负责人: Hua Yan
• 金额: $ 40.55万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584828
• 关键词: Address; Adult; Afferent Neurons; Age; Aggressive behavior; Alzheimer' s Disease; Animal Model; Animals; Anosmia; Ants; Apoptosis; Behavior; Brain; Caspase; Cell Death; Cells; Complex; Defect; Dendrites; Development; Drosophila genome; Drosophila genus; Failure; Fluorescent in Situ Hybridization; G-Protein-Coupled Receptors; Gene Expression; Genes; Genetic; Genome; Human; Immune Response Genes; In Situ Nick-End Labeling; Insecta; Lead; Learning; Lobe; Mammals; Mediating; Memory; Modeling; Molecular; Mus; Mutation; Neuronal Plasticity; Neurons; Nurses; Odorant Receptors; Odors; Organism; Parkinson Disease; Partner in relationship; Pattern; Quality of life; Reaction; Receptor Gene; Role; Schizophrenia; Sensory; Sensory Receptors; Series; Shapes; Smell Perception; Social Behavior; Social Environment; Social isolation; Stains; Structure; System; Testing; Time; autism spectrum disorder; experimental study; injury recovery; mRNA Differential Displays; mutant; nervous system disorder; neural circuit; neurodevelopment; neuron development; neuron loss; neuronal circuitry; neuronal survival; novel; olfactory bulb; receptor; receptor expression; response; sensory system; single-cell RNA sequencing; social; social communication; social deficits; tool; trafficking; transcriptome; transcriptome sequencing

Summary During development and throughout adulthood, humans display strong neuroplasticity, the capacity of adaptive changes of neurons and neural circuits in response to social environments. Plasticity in chemosensory system is essential for learning and memory, social communication and quality of life. Loss of olfactory sensing (anosmia) leads to social isolation, neurological diseases, such as schizophrenia, Alzheimer’s disease (AD) and Parkinson’s disease (PD), and social disorders such as autism. However, the role of neuroplasticity in olfactory- mediated social behaviors is unclear and understudied. We and other labs have developed genetic tools in ants, thereby providing a novel model to study olfactory neuroplasticity in social organisms, as (a) ants are highly social and display complex social behavior; (b) ants display striking neuroplasticity during development and throughout adulthood; (c) neuronal activity is likely required for proper development of olfactory neurons in ants, which is reminiscent of activity-dependent neuronal survival in mammals. The Drosophila genome contains 60 odorant receptor (Or) genes, while 300-500 Or genes have been identified in several ant genomes. In the ant Harpegnathos saltator, mutation in the gene odorant receptor co- receptor (orco), which disrupts the function of all ORs, significantly impacts ant olfaction, and mutant animals display a wide range of abnormal social behaviors. Surprisingly, and unlike other insects, such as Drosophila, this loss of OR functionality during development dramatically reduces the number of odorant receptor neurons (ORNs) and antennal lobe (AL) glomeruli where ORNs project. Further transcriptome analysis suggests that there are two types of ORNs: activity-dependent and activity-independent ORNs. We will use these features in the orco-/- ants and perform a series of molecular and cellular experiments to determine (a) the role of neuronal activity and receptor trafficking in olfactory neuronal survival, and (b) the role of gustatory and ionotropic receptors in neural development.

总结 在发育过程中和整个成年期，人类表现出强大的神经可塑性， 神经元和神经回路对社会环境的适应性变化。化学感受器的可塑性 系统对于学习和记忆、社会交流和生活质量至关重要。嗅觉丧失 （嗅觉丧失）导致社会孤立、神经系统疾病，如精神分裂症、阿尔茨海默病（AD）和 帕金森氏病（PD）和社交障碍，如自闭症。然而，神经可塑性在嗅觉中的作用- 介导的社会行为是不清楚的，研究不足。我们和其他实验室已经在蚂蚁身上开发了遗传工具， 从而提供了一个新的模型来研究嗅觉神经可塑性的社会有机体，因为（a）蚂蚁是高度社会性的 并表现出复杂的社会行为;（B）蚂蚁在发育过程中和整个过程中表现出惊人的神经可塑性 成年期;（c）神经元活动可能是蚂蚁嗅觉神经元正常发育所必需的， 这让人联想到哺乳动物中的活动依赖性神经元存活。 果蝇基因组含有60个气味受体（Or）基因，而300-500个Or基因已被发现。 在几个蚂蚁基因组中被发现。在蚂蚁Harpegnathos saltator中，气味受体基因的突变， 受体（orco），它破坏了所有的OR的功能，显着影响蚂蚁嗅觉，和突变动物 表现出一系列异常的社会行为令人惊讶的是，与果蝇等其他昆虫不同， 在发育过程中OR功能的丧失显著减少了气味受体神经元（ORN）的数量。 触角叶（antennal lobe，AL）肾小球，ORN投射于此。进一步的转录组分析表明， ORN的类型：活性依赖型和活性非依赖型。我们将在orco-/- ants中使用这些特性 并进行一系列分子和细胞实验以确定（a）神经元活动的作用， 受体运输在嗅觉神经元存活中的作用，和（B）味觉和离子型受体在嗅觉神经元存活中的作用。 发展