Physiological identification and characterization of PVN neuronal populations

PVN 神经元群的生理学鉴定和表征

• 批准号: 10220157
• 负责人: GYORGY BUZSAKI
• 金额: $ 43.09万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220157
• 关键词: Adult; Affect; Aggressive behavior; Anxiety; Area; Auditory area; Behavior; Behavioral; Birth; Brain; Caring; Cell Nucleus; Cells; Characteristics; Chronic; Classification; Clinical Trials; Collaborations; Communities; Complement; Dependence; Electrophysiology (science); Emotions; Event; Fiber; Future; Goals; Hippocampus (Brain); Hormones; Human; Hypothalamic structure; Image; Individual; Infant; Knowledge; Lactation; Lateral; Lead; Light; Maternal Behavior; Measurement; Measures; Mental disorders; Methods; Milk Ejection; Mothers; Movement; Mus; Neurons; Neurotransmitters; Output; Oxytocin; Pair Bond; Pathway interactions; Pattern; Peptides; Performance; Peripheral; Pharmacology Study; Photometry; Physiological; Population; Property; Reporting; Research; Retrieval; Signal Transduction; Silicon; Social Behavior; Social Environment; Social Interaction; Source; Spatial Behavior; Structure; System; Testing; Transgenic Mice; Translating; autism spectrum disorder; behavioral study; experimental study; hippocampal subregions; improved; in vivo; individuals with autism spectrum disorder; innovation; interest; neural circuit; neuronal circuitry; neuroregulation; novel; optogenetics; pup; response; social cognition; social engagement; sound; violent attack

Project Summary (Project 2 Co-PIs: Buzsaki, Froemke, Lin, Tsien) The overarching goal of our proposal is to understand how oxytocin signaling engages brain systems to support socio-spatial behavior. A central question is how oxytocin release from hypothalamic neurons affects neuronal activity in target structures and conversely, how these coordinating neurons are embedded and controlled by other neuronal circuits. Toward this goal, the aims of Project 2 is to quantify the firing patterns of oxytocin- releasing PVN neurons under physiological conditions and their relationship with state-dependent firing patterns in partner structures, particularly the hippocampus. These experiments are guided by our overall hypothesis that brain structures involved in various aspects of a maternal behavior, including pup retrieval and defensive/aggressive mechanisms, form an interactive system that includes the PVN and VMH nuclei of the hypothalamus. The first task of Project 2 is it to would out methods to obtain physiological signatures of oxytocin- producing PVN neurons. This will be accomplished by collecting large number of waveform, firing rate dynamics, neuronal interaction and other criteria of the various PVN neurons and verify the classification with a novel, localized light-source optogenetic method. The criteria obtain under this aim will be used in subsequent experiments to identify oxytocin neurons. The next goal is to establish large-scale and highly resilient long-term recordings from the same sets of neurons for repeated social interactions, including violent attacks. We recognize that oxytocin-PVN neurons also release fast neurotransmitters. Therefore, an important goal will be to characterized their firing patterns not only social interactions (Projects 1 and 4) but also in various brain states and in relationship to population patterns, such as the hippocampus. These physiological measurements will be complemented by fiber photometry to measure the overall Ca2+ signal of PVN oxytocin neurons during different behavioral states. Conversely, we will extend the correlational methods with optogenetic induction of synthetic physiological patterns (`ripples') in the hippocampus to examine whether and how PVN and VMH neurons can be influenced by direct or indirect (hippocampus-lateral septum) pathways.

项目摘要（Project 2 Co-Pis：Buzsaki，Froemke，Lin，Tsien） 我们建议的总体目标是了解催产素信号如何使大脑系统与大脑系统相关联 社会空间行为。一个核心问题是催产素如何从下丘脑神经元中释放到神经元 目标结构的活性，相反，这些协调神经元如何嵌入和控制这些协调的神经元 其他神经元电路。为了实现这一目标，项目2的目的是量化催产素的发射模式 在生理条件下释放PVN神经元及其与状态依赖性射击模式的关系 在伴侣结构中，特别是海马。这些实验以我们的整体假设为指导 涉及孕产妇行为各个方面的大脑结构，包括幼犬检索和 防御/攻击性机制，形成了一种交互式系统，其中包括PVN和VMH核的核 下丘脑。 项目2的第一个任务是要获得催产素的生理特征的方法 产生PVN神经元。这将通过收集大量波形，发射速率动态来实现 各种PVN神经元的神经元相互作用和其他标准，并通过小说验证分类 局部光源光遗传学方法。在此目标下获得的标准将在后续使用 实验以鉴定催产素神经元。下一个目标是建立大规模且高度韧性的长期 来自相同一组神经元的录音，以重复进行社交互动，包括暴力攻击。我们 认识到催产素-PVN神经元也释放快速神经递质。因此，一个重要的目标是 描述了他们的发射模式，不仅是社交互动（项目1和4），而且在各种大脑状态下 以及与人口模式（例如海马）的关系。这些生理测量将是 补充纤维光度法，以测量不同的PVN催产素神经元的总体Ca2+信号 行为状态。相反，我们将通过光学遗传诱导合成的方法扩展相关方法 海马中的生理模式（“波纹”），以检查PVN和VMH神经元如何以及如何可以 受到直接或间接（海马 - 外侧隔膜）途径的影响。