Neuronal and genetic imprints of male mating experience

男性交配经历的神经元和遗传印记

• 批准号: 10752146
• 负责人: Renzhi Yang
• 金额: $ 6.91万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2026-07-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10752146
• 关键词: Address; Area; Axon; Behavior; Behavioral; Brain; Candidate Disease Gene; Chronic; Clustered Regularly Interspaced Short Palindromic Repeats; Development; Disease; Electrophysiology (science); Genes; Genetic; Genomic Imprinting; Goals; Health; Human; Hypothalamic structure; Image; Individual; Instinct; Knock-out; Knowledge; Learning; Libido; Link; Measures; Mediating; Memory; Molecular; Molecular Genetics; Molecular Target; Morphology; Mus; Neural Pathways; Neuronal Dysfunction; Neuronal Plasticity; Neurons; Optics; Partner in relationship; Pathway interactions; Performance; Persons; Play; Population; Presynaptic Terminals; Reagent; Reproductive Behavior; Research; Role; Sex Behavior; Slice; Social Behavior; Structure of terminal stria nuclei of preoptic region; Synapses; Synaptic Transmission; Synaptic plasticity; Tachykinin; Techniques; Testing; Therapeutic; Work; behavior test; behavioral study; candidate identification; cell type; cellular targeting; experience; flexibility; genetic manipulation; imaging approach; improved; in vivo; in vivo imaging; injury recovery; innovation; insight; male; mating behavior; multiphoton microscopy; neural circuit; neuromechanism; neuroregulation; novel; optogenetics; postsynaptic; presynaptic; transcriptome sequencing; two-photon; unpublished works

PROJECT SUMMARY Understanding the mechanisms and behavioral relevance of synaptic plasticity has been an active area of research for decades. However, how neural plasticity modulates innate behaviors, such as mating behaviors, is largely unexplored. In addition, cellular and molecular mechanisms of presynaptic neural circuit plasticity remain elusive. Both knowledge gaps will be addressed in this proposal, which focuses on the mechanisms of presynaptic plasticity of a hypothalamic circuit that governs male sexual behavior. Male mice improve in their mating performance after sexual experience, but the underlying neural circuit mechanisms are poorly understood. We observed a dramatic increase of presynaptic axonal termini in the projection from bed nucleus of stria terminalis (BNST) neurons expressing tachykinin 1 (BNSTTac1) to preoptic hypothalamus (POA), a circuit that is essential for male mating behavior. We hypothesize that this structural plasticity in BNSTTac1àPOA projections is critical for the enhancement of mating behavior following sexual experience. We will first characterize the cellular (presynaptic bouton dynamics) and electrophysiological (synaptic transmission efficacy) mechanisms of this plasticity with chronic in vivo imaging and slice recording. Further, we aim to dissect the molecular pathways underlying this plasticity with deep RNA sequencing and genetic manipulations. Lastly, we will perform behavioral tests to study how this plasticity modulates the display of male sexual behaviors. Our results will uncover the specific mechanisms modulating a key brain circuit for controlling mating behavior, which may inspire potential therapeutic approaches to alleviate low libido in humans.

项目概要 了解突触可塑性的机制和行为相关性一直是一个活跃的领域 然而，神经可塑性如何调节先天行为（例如交配行为）的研究已经存在了数十年。 此外，突触前神经回路可塑性的细胞和分子机制仍未被探索。 该提案将解决这两个难以捉摸的知识差距，该提案的重点是机制。 控制雄性性行为的下丘脑回路的突触前可塑性得到改善。 性经历后的交配表现，但潜在的神经回路机制尚不清楚。 我们观察到从纹状体床核投射的突触前轴突末端显着增加 终末 (BNST) 神经元将速激肽 1 (BNSTTac1) 表达至视前下丘脑 (POA)，该回路是 我们勇敢地承认 BNSTTac1àPOA 预测中的这种结构可塑性是至关重要的。 对于性经历后交配行为的增强至关重要我们将首先描述细胞的特征。 （突触前波顿动力学）和电生理学（突触传递功效）机制 此外，我们的目标是剖析分子途径。 最后，我们将通过深度 RNA 测序和基因操作来实现这种可塑性。 我们的结果将通过行为测试来研究这种可塑性如何调节男性性行为的表现。 揭示调节控制交配行为的关键大脑回路的具体机制，这可能 缓解人类性欲低下的潜在治疗方法。